TRANSORAL ROBOTIC SURGERY (TORS) - Alberta€¦ · TRANSORAL ROBOTIC SURGERY (TORS) MINI-REVIEW 5...

TRANSORAL ROBOTIC SURGERY (TORS)

MINI-REVIEW

5 OCTOBER 2017

Submitted to: Submitted by:

The Alberta Health Technologies Decision Process Health Technology & Policy Unit

Research & Innovation Branch School of Public Health

Innovation and Strategic Operations Division University of Alberta

[email protected]

Alberta Health

Production of this document has been made possible by a financial contribution from Alberta Health under the auspices of the

Alberta Health Technologies Decision Process: the Alberta model for health technology assessment and policy analysis. The

views expressed herein do not necessarily represent the official policy of Alberta Health.

Authors’ conflict of interest statements: None declared.

Transoral Robotic Surgery (TORS) October 2017

© 2017 Government of Alberta pg 1

Executive Summary

Oropharyngeal cancer is a malignant tumour that can metastasize to other parts of the body. The most

influential risk factor for this disease is tobacco smoking, and it affects more men than women. In 2013,

the number of Canadians who were diagnosed with or died from oropharyngeal cancer was 180 and

131, respectively. Treatment options include radiotherapy (RT), chemoradiotherapy (CRT) and surgery

(open, trans-oral laser microsurgery (TLM) or trans-oral robotic surgery (TORS)). This report provides a

review of such treatments within the context of the Quadruple Aim framework of Alberta Health

Services.

A systematic review of 28 clinical studies of TORS was conducted. Seven compared TORS to another

treatment (5 open surgery, 2 TLM). The remaining 21 were of TORS only. The overall quality of the

studies was low. Information related to the “learning curve” and surgeons’ experience with TORS was

obtained from literature. The manufacturer provided data on the availability of TORS across Canada.

Estimates of direct costs were obtained through analyses of Alberta Health administrative data sets.

What matters most to patients?

Adverse events: Adverse events were similar for TORS and open surgery (post-operative bleeding: 6%

to 23% with TORS and 13% with open surgery; airway edema: 20% with TORS and 19% with open

surgery; pulmonary embolism: 8% with TORS and 3% with open surgery; hematoma: 2% to 6% with

TORS compared to 3% with open surgery; and fistula: 7% with TORS and 6% with open surgery). In a

study comparing TORS with TLM, adverse events occurred in three patients (6%) with TORS and three

patients (18%) with TLM.

Infections: One study reported a statistically significantly lower infection rate with TORS (9%) compared

to open surgery (22%). Results of two studies that compared TORS and TLM demonstrated similarly low



infection rates. Across the non-comparative studies low infection rates were also found (3% to 11% in

five studies and 0% in six studies).

Blood transfusions: In one study, transfusion rates for TORS and open surgery were the same (17%).

Across the non-comparative studies, the transfusion rate was 0%.

Conversions to open surgery: In one comparative study, 2% of TORS patients were converted to the open

procedure, versus 12% of TLM patients (statistically significant difference). In the non-comparative

studies, conversion rates ranged from 0% to 2%.

Blood loss: The estimated blood loss was considerably higher with open surgery (331 ml) than with TORS

(49 ml) (statistically significant difference), but was similar between TORS and TLM.

Reconstruction: One study of patients with recurrent cancer showed that reconstructive surgery was

required in a statistically significantly higher proportion of patients who underwent open surgery (75%)

compared to TORS. In another study, one patient underwent reconstruction in the open surgery group,

while none required such treatment in the TORS group.

Pain: None of the comparative studies assessed pain. In one non-comparative study, patients reported

high levels of pain after surgery, which had significantly diminished by six and 12 months.

Margin status: Compared to TORS, rates of positive surgical margins were higher for open surgery.

However, there were no statistically significant differences between TORS and TLM. Across all studies,

the proportion of TORS patients with positive surgical margins ranged from 0% to 14%.

Nasogastric tube placement and time to oral intake: Excluding prophylactic placements, gastric tube

placement was required for 0% to 77% of TORS cases, and mean/median time to oral intake ranged

from five to 16 days. One study reported a statistically significantly longer time to oral intake after open

surgery when compared to TORS.

Percutaneous endoscopic gastrostomy (PEG): For recurrent cases, rates of PEG placement and chronic

dependency were significantly higher with open surgery. However, there were no differences between



TORS and TLM. Across all studies, initial PEG rates ranged from 0% to 46% for TORS patients. Overall,

chronic PEG dependency was low (0% to 6%) at one month to 61 months of follow-up.

Swallowing function: None of the comparative studies assessed swallowing function. Results of the non-

comparative studies showed that TORS was associated with some impairment in swallowing function

shortly after surgery; however, swallowing returned to normal after one year.

Tracheostomy: Of the three comparative studies that reported higher rates of initial tracheostomy after

open surgery, two showed no statistically significant differences after 6 to 20 months of follow up. In a

single study of TORS versus TLM, there was no statistically significant difference in tracheostomy rates.

Across all studies, rates for TORS patients ranged from 0% to 59%, but fell to 0% to 2% after three to 51

months of follow-up.

Voice/speech function: One comparative study assessed voice function at one year and found no

difference between patients who had open surgery and those who had TORS. Among the non-

comparative studies, one showed no significant deterioration of voice six and 12 months after surgery,

while two reported that although speech function was still good at 12 months, it had statistically

significantly worsened at both six and 12 months.

Health-related quality of life (HRQOL): No studies compared HRQOL between TORS and open surgery or

TORS and TLM. Among the non-comparative studies, there were no statistically significant differences in

pre- and post-operative scores at six and 12 months, suggesting that with TORs, quality of life is

maintained. However, in one study, a significant decline in satisfaction with eating functions related to

dryness of mouth (which resulted in a need to change eating habits) was reported at 12 months.

Aesthetic outcomes: No significant differences between measurements of aesthetic function

preoperatively and one to two years after TORS were found.

Disease recurrence: In one comparative study with balanced TORS and open surgery arms, one patient in

each arm developed a metastasis after a mean follow up of 20 months. In a study of TORS versus TLM,



at one year of follow-up, no statistically significant differences in loco-regional recurrence and

metastasis rates between the two procedures were found. Across all studies, TORS patients

experienced local recurrence rates of 0% to 8%, regional recurrence rates of 0% to 12%, and metastasis

rates of 0% to 4% after 12 to 33 months of follow-up.

Disease-free survival: In one study of TORS versus open surgery, disease-free survival at one year was

statistically significantly higher among patients who received TORs (TORs: 94%; open surgery: 85%).

One study comparing TORS and TLM reported similar rates for the two procedures (TORS:100%; TLM:

94%). Regarding disease-free survival at two years, in two comparative studies of TORs and open

surgery, higher rates were associated with TORS. One study also assessed disease free survival at three

years and reported a statistically significantly higher rate for patients who underwent TORS.

Mortality: None of the studies reported statistically significant differences in mortality across surgical

procedures.

Overall survival: One comparative study of TORS and open surgery demonstrated higher overall survival

at two years following TORS (TORS: 74%; open surgery: 43%), while a second study reported similar

rates (TORS: 97%; open surgery: 100%). Across all studies, overall survival at two and three years post

TORs ranged from 90% to 100% and from 89% to 98%, respectively.

What matters most to staff?

Surgeon’s health: In preference-based studies comparing robotic surgery, in general, to open surgery, in

general, for a broad range of procedures, surgeons performing the open surgery were significantly more

likely to report acute and chronic pain and further treatment for serious injuries.

What matters most to the system?

Set-up and operative times: Median/mean time for TORS set-up ranged from 9 to 59 minutes and

decreased with the number of cases performed. Operative time was defined differently across studies.

Nonetheless, three studies reported longer operative times for open surgery compared to TORS; in one



study, the difference was statistically significant. No statistically significant difference in operative times

between TORS and TLM were found.

Length of stay: Across studies of TORS versus open surgery, the latter was associated with statistically

significantly longer hospital stays. However, in the two comparative studies of TORS and TLM, lengths of

stay for the two procedures were similar.

Readmission rate: No significant differences were reported between TORS and TLM. Overall,

readmission rates for TORS cases ranged from 3% to 15%.

Access: TORS has been provided at the University of Alberta Hospital for the past 2 years. Approximately

30 patients have been treated to date. Across Canada, nine centres perform TORS. The estimated

annual demand for TORS in Alberta is 40 procedures. This number can be accommodated at the

University of Alberta Hospital.

Direct costs: The average per case cost of a TORS procedure in Alberta in 2016 was $94,124, compared

to $84,744 for open surgery. These costs include physician fees, inpatient costs, and in the case of TORS,

those associated with the robot (system and disposables).



Table of Contents Executive Summary ....................................................................................................................................... 1

Abbreviations ................................................................................................................................................ 8

Glossary ....................................................................................................................................................... 10

Introduction ................................................................................................................................................ 12

Objectives ................................................................................................................................................... 13

Methods ...................................................................................................................................................... 13

Literature search ..................................................................................................................................... 13

Quality assessment of studies................................................................................................................. 15

Data analysis and synthesis .................................................................................................................... 16

Results ......................................................................................................................................................... 16

Results of the literature search ............................................................................................................... 16

Overall description of included studies .............................................................................................. 17

Overall quality of included studies...................................................................................................... 21

What matters most to the patient ...................................................................................................... 22

What matters most to staff ................................................................................................................ 30

What matters most to the system ...................................................................................................... 30

Conclusions ......................................................................................................................................... 32

Appendices .................................................................................................................................................. 92

Appendix A. Literature search ................................................................................................................ 92

Appendix B. Included studies ................................................................................................................ 103



Appendix C. Excluded studies ............................................................................................................... 109

Appendix D. Quality of included studies ............................................................................................... 111

Figure 1. PRISMA Diagram of literature search and study selection for the clinical effectiveness review 17

Table 1. Study eligibility criteria for the review on safety and effectiveness of TORS ............................... 14

Table 2.Inclusion and exclusion criteria of participants. ............................................................................ 33

Table 3. Characteristics of Participants ....................................................................................................... 39

Table 4. Characteristics of procedure ......................................................................................................... 49

Table 5. Safety ............................................................................................................................................. 58

Table 6. Operative and post-operative outcomes ...................................................................................... 63

Table 7. Swallowing-related outcomes ....................................................................................................... 67

Table 8. Speech function ............................................................................................................................. 73

Table 9. Health-related quality of life (HRQOL) outcomes ......................................................................... 76

Table 10. Oncological Outcomes. ............................................................................................................... 81

Table 11. Survival Outcomes ....................................................................................................................... 85

Table 12. Resource related outcomes ........................................................................................................ 89



Abbreviations

AHS= Alberta Health Services

BOT= Base of tongue

CRT= Chemoradiotherapy

CI= Confidence interval

CS= Communication score

DS= Dysphagia score

EBL= Estimated blood loss

FOSS= Functional outcomes of swallowing scale

FUP= Follow-up

HNC= Head and neck cancer

HNCI= Head and neck cancer inventory

HPV= Human papillomavirus

HPV+= Human papillomavirus positive test

HPV-= Human papillomavirus negative test

HRQOL= Health-related quality of life

IQR= Interquartile range

LRRFS= Locoregional recurrence-free survival

MDADI= MD Anderson dysphagia inventory

MCS= Mental component summary

MFS= Metastasis-free survival

MI= Myocardial infarction

NA= Not applicable

NCDB= National Cancer Database



ND= Neck dissection

NG= Nasogastric

NR= Not reported

OPSCC= Oropharyngeal squamous cell carcinoma

PCS= Physical component summary

PEG= Percutaneous endoscopic gastrostomy

PRISMA= Preferred Reporting Items for Systematic Reviews and Meta-analysis

PSS-HN= Performance status scale for patients with head and neck cancer

ROB= Risk of bias

RT= Radiotherapy

SD= Standard deviation

SF-8= 8 Item short form health survey

STN= Soft tissue necrosis

TORS= Transoral robotic surgery

TLM= Transoral laser microsurgery

UTI= Urinary tract infection

UW-QOL= University of Washington quality of life questionnaire

VHI-10= Voice handicap index-10

WHO= World Health Organization



Glossary

Adjuvant therapy = additional treatment (i.e. radiotherapy, chemoradiotherapy) given after the primary

treatment to lower changes of cancer recurrence.

Adverse event = an unwanted effect associated with the use of a treatment or intervention

Case-control study = an observational study that compares individuals with a condition (cases) to those

from a similar population without the condition (controls).

Case report = an account of one patient that typically describes their presentation, diagnosis, treatment

and outcomes.

Case series = a study that reports on outcomes for a series of individual patients who have received an

intervention (i.e., with no comparator group).

Cohort study = an observational study where two or more groups of people with similar characteristics

but exposed to different interventions (or an intervention versus no intervention) are followed over

time and compared.

Confidence interval (CI) = the amount of uncertainty regarding the true effect of an intervention.

Typically a 95% confidence interval (CI) is used, which indicates that the results are likely to be within

this range approximately 95% of the time.

Close surgical margins = description of pathological tissue in which tumor cells are found close to the

edge of the tissue, suggesting more surgery may be required to completely remove tumor.

Head and neck cancer = a group of cancers arising from the mouth, nose, throat, sinuses, salivary glands

and lymph nodes located in the neck

Meta-analysis = the use of statistical methods in a systematic review to combine results from different

studies in order to estimate of the overall effect of an intervention.

Nasogastric tube (NG) = a flexible tube that is inserted through the nose, past the throat and down to

the stomach. It can be used to remove content of the stomach or administering drugs and for feeding



Neck dissection (ND) = a surgical procedure to remove lymph nodes in the neck to control for lymph

node metastasis

Non-randomized controlled trial (non-RCT) = a study in which participants are not assigned by chance to

different groups (e.g., researchers assign every second individual to the treatment group).

Oropharyngeal cancer = a disease in which tumor cells form in the tissue of oropharynx. It includes the

tonsils, posterior pharyngeal wall, base of tongue and soft palate.

Oropharynx = part located in the middle portion of the pharynx, right behind the mouth.

Percutaneous endoscopic gastrostomy (PEG) = a procedure in which a tube is placed through the

abdominal wall and into the stomach. It allows for enteral nutrition bypassing the mouth and throat

Positive surgical margins = description of pathological tissue in which tumor cells are found at the edge

of the tissue, suggesting that all of the cancer has not been removed

Randomized controlled trial (RCT) = a study in which participants are assigned by chance (at random)

into groups (typically a study group and a control group). The groups are managed in the same way

except for their exposure to the intervention or risk factor being studied.

Surgical margin = the border of the tissue removed in surgery. The margin is considered positive when

cancer cells are found at the edge of the tissue; Positive surgical margin rate is the number of patients

with positive surgical margin divided by the total number of patients undergoing surgery.

Systematic review (SR) = a critical assessment and synthesis of the results of all studies addressing a

particular research question.

TNM system= a classification system used to describe the extent of tumor cancers. The T refers to the

size and extent of the tumor. The N refers to the number of positive regional lymph nodes. The M refers

to presence of metastasis.

Tracheostomy = a surgically created hole into the windpipe to assist breathing



Transoral laser microsurgery (TLM) = a minimally invasive surgical procedure that uses CO2 laser surgical

tool to remove tumors located in the throat

Introduction

Oropharyngeal cancer is a malignant tumour that can metastasize to other parts of the body. The most

influential risk factor for this disease is tobacco smoking, and it affects more men than women. In 2013,

180 Canadians were diagnosed with oropharyngeal cancer and 131 individuals died from it. The

treatment options are radiotherapy (RT), chemoradiotherapy (CRT) and surgery (open, trans-oral laser

microsurgery (TLM) or trans-oral robotic surgery (TORS)).

This review of the alternatives for treatment was conducted within the Quadruple Aim framework of

Alberta Health Services. Specifically, the focus on this review was to determine, with respect to TORS,

What matters most to patients

What matters most to staff, and

What matters most to the system



Objectives

To assess health and resource-related outcomes for transoral robotic surgery (TORS) compared to

conventional open surgery, transoral laser microsurgery (TLM), radiotherapy (RT) and

chemoradiotherapy (CRT) for the treatment of oropharyngeal carcinoma.

Methods

A systematic review of published peer-reviewed studies was completed to assess TORS as a treatment

for oropharyngeal carcinoma. All steps complied with the Cochrane methodological guidelines (1).

Additional information was obtained from the literature on surgeon experience with TORS and other

surgeries for this condition and from the manufacturer of the da Vinci robotic surgery system. Cost data

from Alberta Health datasets were used to estimate costs.

Literature search

A comprehensive literature search was conducted to identify relevant primary studies on the use of

robot-assisted surgery for the treatment of oropharyngeal carcinoma. To accomplish this, structured

search strategies were developed and applied to the following bibliographic databases: PubMed

(MEDLINE and other sources), EMBASE, Web of Science, Clinical Trials.gov, The Cochrane Library,

CINAHL, EconLIT, PsycINFO, and the Centre for Reviews and Dissemination (DARE, NHS EED, and HTA).

The strategies combined relevant keywords with controlled vocabulary terms (Medical Subject Headings

(MeSH) and EMTREE terms) such as, robotic surgical procedures, minimally invasive surgical procedures,

and transoral surgery. Keywords included robotic surgery, robot-assisted surgery, as well as da Vinci. Full

details of the literature search are presented in Appendix A. All searches were limited to human studies

reported in English. No study design filters were applied.



Grey literature (i.e., unpublished studies and HTA reports) was identified through searches of 1) the

websites of relevant associations and HTA agencies, 2) dedicated grey literature databases (Grey

Literature Collection, NHS Evidence, and the NLM Gateway), 3) guidelines databases, and 4) the internet

(Google search engine). Monthly update searches in PubMed and Google scholar alerts were also

performed throughout the project to capture any additional studies published after the initial search

period. Finally, for completeness, a manual search of the reference lists of relevant papers located

through the electronic search was conducted.

Results from each of the searches were compiled and entered into a single Reference Manager® (v. 12)

database, after which duplicate citations were removed. Two reviewers independently screened the

titles and abstracts to identify studies for full-text review. Both reviewers retrieved and assessed the

full-text articles for inclusion and exclusion according to pre-defined eligibility criteria (Table 1).

PubMed was searched for published literature on surgeon experience with TORS, to identify studies of

the learning curve and surgeon perspectives on the surgical treatment of oropharyngeal cancer.

Table 1. Study eligibility criteria for the review on safety and effectiveness of TORS. Parameter Inclusion criteria Exclusion criteria

Setting Publications in English

Any health care facility performing procedure

Abstracts

Participants Adults (age>18 years old) undergoing treatment for

malignant oropharyngeal carcinoma

Oropharyngeal carcinoma was defined as a primary

tumor arising in the soft palate, tonsils, base of

tongue (BOT) and pharyngeal wall

Participants with other types of head and neck

cancer: hypopharyngeal, oral cavity, laryngeal

and nasopharyngeal cancer

Intervention TORS with the da Vinci surgical system

Comparator Conventional open surgery

TLM

RT for early stages of cancer

CRT for advanced stages of cancer

RT as a single modality for advanced stages of

cancer

CRT as a single modality for early stages of

cancer

Outcomes Adverse events

Infection rates

Blood transfusion

Conversion to open

Equipment failure

Estimated blood loss

Reconstruction

Pain

Margin status

Operative time

Studies without any defined clinical outcomes

Studies with no relevant clinical outcomes



Length of hospital stay

Readmission rate

Time to oral intake

Percutaneous endoscopic gastrostomy (PEG) rate

Tracheostomy

Swallowing function

Speech function

Aesthetic outcome

Health-related quality of life (HRQOL)

Time to return to work

Disease recurrence

Disease-free survival rate

Mortality rates

Overall and disease-specific survival rates

Study design Randomized and non-randomized controlled trials

(RCTs and non-RCTs)

Single arm trials

Cohort studies

Case-control studies

Case series

Case series with sample size <10

Data extraction

Each reviewer extracted information from studies using a standard data extraction form. The elements

extracted were: study design, setting, methods; sample size and baseline characteristics; details of the

intervention and comparator (where applicable); and outcome measures (listed in Table 1) and findings.

Quality assessment of studies

The methodological quality of non-RCTs studies was evaluated using the Downs and Black checklist (2).

This is a 27 item validated tool for scoring studies over five domains: 1) reporting quality (10 items, one

scoring up to 2 points); 2) external validity (3 items) – to assess generalizability of findings; 3) study

conduct bias (7 items) – to identify bias in the intervention and outcome measure(s); 4) selection bias (6

items) – to determine bias from sampling or assignment of patients to treatment or intervention groups;

and power of the study (1 items) – to determine if findings could be due to chance. Each item is scored

as either ‘1’ if the condition is met or ‘0’ if it is not met or is impossible to determine. A total score of 28



is possible (if all conditions are met). The final question on the power of the study was excluded since

none of the included studies reported it.

The GRADEpro tool (Grading of Recommendations Assessment, Development and Evaluation) was used

to assess the overall quality of the body of evidence for key outcomes (3). Up to seven outcomes are

recommended by the GRADE Working Group. A GRADE rating is applied for each outcome, and the

quality may differ between outcomes. The quality of outcomes is rated over 7 domains: study design,

risk of bias, inconsistency, indirectness, imprecision and other factors including publication bias, a large

effect size, a dose response gradient and other plausible confounding. This approach can yield four

grades ranging from very low to high confidence in the overall quality of evidence.

Data analysis and synthesis

Data extracted from included studies were tabulated to facilitate quantitative and qualitative analysis.

Data were reviewed and assessed for presence of heterogeneity and the potential for meta-analysis.

Characteristics of included studies and findings were synthesized narratively.

Results

Results of the literature search

A total of 1,231 discrete citations were identified through the literature searches, and 47 full-text

articles were retrieved for review. Of these 28 published studies met eligibility criteria. The literature

search results are described using the Preferred Reporting Items for Systematic Reviews and Meta-

analysis (PRISMA) flow diagram show in Figure 1. A summary of characteristics of included studies is

presented in Appendix B. Excluded studies and rationales for exclusion are listed in Appendix C.



Overall description of included studies

The 28 included studies comprised seven comparative and 21 non-comparative studies involving TORS

for the treatment of oropharyngeal carcinoma. Studies were conducted between 2001 and 2016 with 21

of them located in the USA. The remaining studies were conducted across Europe (4), South Korea (2)

and Canada (1). None of the comparative studies were RCTs; five studies compared TORS with open

surgery (total of 196 and 202 patients respectively)(4-8), and two compared TORS with TLM (386 and

161 patients, respectively)(5;9). A total of 1139 patients were enrolled in the 21 non-comparative

studies (13 case series(9-21) and 8 single-arm trials(22-29)). No study had RT or CRT as the comparator

or as the primary treatment; however, in 1 comparative study and 16 non-comparative studies, some

patients received RT or CRT as adjuvant therapy as well.

Records identified through database searching= 1,834

Additional records identified through other sources = 86

Records after duplicates removed = 1,231

Titles and abstracts reviews

Full text articles assessed for eligibility = 47

Studies meeting inclusion criteria = 28

Records excluded = 1,184

†Reasons for exclusion of studies: population not relevant or unclear; patients already included in another

study; outcome not relevant or unclear; intervention not relevant or unclear; comparison group not relevant

Excluded studies† = 19

Figure 1. PRISMA Diagram of literature search and study selection for the clinical effectiveness review



Patient characteristics

Table 2 and 3 describe the inclusion and exclusion criteria for selecting participants and their

characteristics in the studies.

Apart from two, all studies provided information on age and gender (10;29). The mean/ median age

across studies was similar ranging from 55 to 65 years among TORS and from 58 to 61 years in the

comparison groups. The majority of participants in all studies were male with (54% to 94%). None of the

studies applied an upper age limit or gender as exclusion criteria.

Fifteen studies reported on smoking status as either a categorical variable (i.e. current, former and

never)(5;12-14;17-19;22;25;28) or measured in pack years (4;10;11;23;30). The number of current/

former smokers varied across studies from 33% to 95%, and 29% to 59% of participants were considered

heavy smokers (≥ 10 pack years).

Fourteen studies reported on HPV status measured through expression of p16 or an HPV-DNA test. (4-

6;9-13;18;20;22;23;25;31) Two studies only included patients who were positive for p16.(10;11) Based

on the presence of p16, HPV was present from 51% to 100% of patients. However, four studies reported

on HPV positivity based on presence of p16 and HPV-DNA and found inconsistences between the two

values, suggesting a possibility of misclassification.(13;18;20;23) A population-based cohort reported

low rates for HPV due to a large number of missing values.(31)

Two comparative studies (7;8) with open surgery included only participants with recurrent cancer, while

all studies on TLM (30;31) and eleven non-comparative studies excluded participants with previous head

and neck cancer.(10;14;18-21;23;24;27-29). When reported, the rate of prior treatment for head and

neck cancer was 3% to 24% and involved surgery, RT and CRT as single or combined modalities.

All but two studies provided information on the anatomical subsite of oropharyngeal carcinoma.(7;17)

While two studies included only patients with cancer located in the tonsils(6;29), two other studies had



only patients with base of tongue (BOT) cancer.(24;26) The remaining studies had cancers most

commonly in the tonsils (36% to 80%), followed by BOT cancer (20% to 59%).

All studies described the size of the main tumor (T stage). Five studies only included T1 and T2 stages

(tumor size≤ 4cm).(8;21;23;24;26) Five studies excluded patients with T4 tumors, though two of them

included some cases of T4a tumors. However, all studies excluded T4b tumors.(6;20;25;27;30) The

remaining studies comprised mainly patients with T1 (16% to 59%) or T2 (38% to 59%) tumors. There

were some cases of T3 (3% to 24%) and T4 (0% to 20%).

One study only included patients with N0 or N1 stages on clinical images.(23) When reported, most

studies had higher rates of N2 tumors (8% to 79%) and wide range of rates for N0 (2% to 92%) and N1

(0% to 48%). There were very few cases of N3 tumors (0% to 17%).

Two studies included only patients at advanced stages of oropharyngeal cancer defined as stages III to

IV.(4;27) In contrast, one study excluded patients at stage IV and another one specifically excluded those

with stage IVB.(23;31)When reported, the remaining studies included more patients with advanced

stages (range: 8% to 100%) and only three studies reported higher rates of early stages of cancer

defined as stages I and II (range:0% to 92%).(8;24;26)

Characteristics of procedure

Table 4 describes the characteristics of the treatment for oropharyngeal cancer including: the robot

model used during studies, description of neck dissection, adjuvant therapy and surgeon’s learning

curve.

Model of robot: The specific model of robot used was reported in only four studies; da Vinci S and da

Vinci Si were each used in two studies.

Neck dissection: The types of neck dissection were poorly reported and the indication for neck

dissection varied widely across studies. When reported, in most studies neck dissection was performed

during the same operation as the surgical procedure for tumor resection. Only six studies(17;19-



21;27;29) had patients undergoing neck dissection as a second surgery days after TORS and three

studies (8;13;22) reported a mix of neck dissections occurring at the same time or at a different day

from tumor resection. Three comparative studies reported no statistically significant differences in rates

of neck dissection between open surgery and TORS.(4-6;8) However, one study reported a statistically

significant difference with more patients in the TORS group undergoing neck dissection compared to

TLM. (31) Overall, when reported, most patients had a neck dissection with rates ranging from 54% to

100%.

Adjuvant therapy: Three studies excluded patients receiving adjuvant therapy(10;12;24), while one

study only included patients receiving adjuvant RT or CRT.(14) The most common indications for

adjuvant therapy with RT described in the studies after surgery included: T3-4 tumor; close margins;

multiple nodes; and perineural or lymphovascular invasion. Some studies also mentioned the presence

of grade 4/4 disease, desmoplasia or atypical metastatic pattern as an indication for RT. The range of RT

dose (60Gy to 74Gy) at primary tumor resection was similar across studies. When reported, the main

indications for CRT were positive margins and/ or extracapsular spread. Most studies included treatment

with cisplatin and in some cases other drugs such as cetuximab and carboplatin were used in

combination with taxol. Excluding studies with adjuvant therapy as an eligibility criterion, the number of

patients receiving it varied widely from 8% (in a study with most participants at early stages of cancer) to

93% (in which 89% of patients had advanced cancer). Four studies reported that between 2% and 23%

of patients declined further treatment with RT and/ or CRT. (13;23;27;28)

Surgeon’s experience (learning curve): Six studies provided information on the surgeons’ experience with

TORS at the beginning of studies.(5;6;9;16;24;28) Only two studies (both non-comparative) analyzed the

surgeon’s learning curve for TORS. Both studies reported differences in set up and operating time

between the first cases and subsequent ones. One study suggested 27 to 39 procedures as required for

the learning curve, although when using surgical margins as the outcome to assess the learning curve,



surgeons were considered experienced after 25 to 27 cases. No differences in length of hospital stay and

readmission rates were found between surgeons at the initial and final experience stages for TORS.

None of the studies compared the learning curve between TORS and other surgical procedures (open

surgery and TLM) for oropharyngeal cancer.

Overall quality of included studies

The following key outcomes were selected to assess the quality of evidence using the GRADE approach:

overall survival at 1 year; disease-free survival rate at 1 year; gastrostomy tube dependency;

tracheostomy tube dependency; swallowing function; blood transfusion and adverse events. Further

details are reported in Appendix D.

The overall quality of evidence of TORS compared to open surgery and TLM was very low.

Reporting bias: All comparative studies provided a clear description of hypothesis, outcomes and

characteristics of patients. Four studies also gave provided an adequate description of the surgical

procedure for TORS and control groups (open or TLM).(4;6;7;30) p-values were reported in all cases but

two studies failed to provide a clear description of the main findings. (4;31) Further, two studies did not

provide estimates of random variability (i.e. standard deviation, range).(4;7)

Selection bias: No RCT was identified in the literature search. Most comparative studies recruited

patients receiving different interventions from the same population. However, apart from two studies,

all groups were recruited over different periods of time. (6;31)

Performance and observer bias: Surgeons were not blinded due to the visible differences in the

interventions and the nature of the clinical procedure. Further, none of the patients were blinded to the

intervention they received. Only one study attempted to blind the data analyst to the patient’s

outcomes.(5) Since the comparative studies mainly reported objective measures (e.g., hospital stay,

recurrence), the influence of performance and observer bias was low.



Attrition bias: There was a low risk of noncompliance and misclassification with the treatments for

oropharyngeal carcinoma. Apart from two studies with a small loss to follow up, studies did not provide

description of patients lost to follow up and whether there was an attempt to take that into account

during data analysis.(7;31)

External validity: One study analyzed data from a US population database.(31) The remaining studies did

not report the characteristics of the source population or whether the final sample of patients was

representative of the entire population.

Other sources of bias/ confounding: One study did not use appropriate statistical tests for a matched

retrospective cohort.(4) Further, most studies did not fully describe principal confounders and failed to

control for them during selection of patients or at the data analysis stage.

What matters most to the patient

Safety

Table 5 presents data on safety including: adverse events; infection rate; blood transfusion; conversion

to open procedures and equipment failure rates.

Adverse events: Twenty studies provided data on adverse events after TORS procedures.(4;6;6-

8;10;13;14;16;18;19;21-30) Postoperative bleeding ranged from 6% to 23%. Studies reported on several

respiratory complications: airway edema (20%); pulmonary edema (2%); and pulmonary embolism (8%).

Other adverse events reported were hematoma (2% to 6%) and fistula (3% to 7%).

Trismus (5% to 7%), soft tissue necrosis/ ulcers (18% to 28%), mucositis (89%), xerostomia (40%) and

shoulder pain (38%) had higher rates, but were most likely related to the entire treatment for

oropharyngeal cancer which may have included surgery and adjuvant therapy with RT and CRT.

In one comparative study on TORS and TLM, 3 patients (18%) in the TORS group had some adverse

event, while 1 (6%) patient had one complication after TLM. (30)



With regards to open surgery, similar to TORS, studies reported on: postoperative bleeding (13%);

hematoma (3%); fistula (6%); and respiratory problems including airway obstruction (10%), pulmonary

embolism (3%) and airway edema (19%). Other surgical complications were: revision of reconstructive

surgery (7% to 11%); malunion (3% to 7%) and abscess (10%). One study found no statistically significant

differences in rates of fistula, airway edema and postoperative bleeding between TORS and open

surgery.(7)

Infection rate: Four comparative studies (6-8;30) and eleven non-comparative studies described

infection rates after the surgical procedure.(10;16;18;19;21;23;25-29) One of the comparative studies

reported higher infection rates with open surgery (22%) than TORS (9%); the difference was statistically

significant (p=0.03).(7)

Studies comparing TORS and TLM described similar and low infection rates after both surgeries. (6;30)

The main infection reported was pneumonia (3% to 10%), mainly caused by aspiration. Overall, the

infection rate was low with six studies reporting rates of 0%.(6;16;18;19;21;23;25;26)

Blood transfusion: One study reported identical blood transfusion rates between TORS (17%) and open

surgery (17%) for advanced oropharyngeal cancer.(4) None of the comparative studies reported on

blood transfusion rates for TLM. When reported, non-comparative studies reported rates of blood

transfusion as 0% for TORS in early and advanced tumor stages. (19;24)

Conversion to open procedure: One study assessed conversion rates during TORS and TLM(31), and

found 12% of TLM patients were converted to open, while only 2% of TORS required conversion. This

difference was statistically significant (p<0.001). Overall, when reported, the rate of conversion to open

procedure for TORS was 0% to 2%.(4;14;18;31)

Equipment failure: None of the included studies reported on equipment failure rates for TORS.



Health outcomes

1. Operative -Table 6 tabulates the findings for operative outcomes

Estimated blood loss: One study compared the estimated blood loss between TORS and open surgery for

recurrent cases and found a statistically significant higher blood loss with the open procedure compared

to TORS (331ml vs 49ml, p<0.001). But there was no statistically significant difference between TORS

and TLM in this measure (170ml vs 200ml, p=0.32) with both groups having a high proportion of patients

with advanced stage tumors. (30) While two non-comparative studies (16;28) reported low mean/

median estimated blood losses of 10 and 13ml, the remaining studies reported mean/median values

from 88ml to 220ml with higher ranges in studies which had more patients with advanced stages (III and

IV) of oropharyngeal carcinoma.(30)

Reconstruction: One comparative study on recurrent cancer found that 75% of patients undergoing

open surgery required reconstructive surgery while none of patients in the TORS group required it. This

difference was statistically significant (p<0.001). (7) Further, another study reported one patient

requiring a secondary revision surgery due to complications after open surgery but none after TORS. (6)

One comparative study reported no reconstructive surgery after TORS or TLM.(30)

Non- comparative and comparative studies reported on a TORS rate for reconstructive surgery ranging

from 0% to 63%. Higher rates were associated with studies which also included recurrent cases.

2. Post- operative- Table 6 describes the findings for post-operative outcomes.

Pain: Two non-comparative studies measured pain in patients undergoing TORS. (12;14) One reported

high levels of pain 1 month after surgery and significant improvements 6 months and 1 year after

surgery; patients felt less pain over the course of the study (12). The second study found that the

development of soft tissue necrosis due to the combined treatment of TORS and RT led to 24% of

patients complaining about pain with 21% requiring opioids to alleviate it.(14)



Margin status: When reported, the definition of positive and close margins varied from at least 0 to

4mm of histopathologically normal tissue. Eleven studies reported on positive surgical margin rates

associated with TORS.(4;6;7;9;13;14;18;23-25;30;31) Three studies compared margin status between

TORS and open surgery and all reported higher positive surgical margins with open surgery.(4;6;7)

However, only one of them, which recruited only recurrent cases, found the difference to be statistically

significant.(7)

Studies reported no differences in positive surgical margin rates between TORS and TLM. (30;31)

The rate of TORS for positive surgical margins was 0% to 14% with lower rates associated with studies

having a higher proportion of early staged cancer cases.

3. Short and long-term outcomes

Nasogastric tube placement and time to oral intake: Table 7 presents rates of nasogastric tube

placement, time to oral intake and percutaneous endoscopic gastrostomy (PEG). None of the studies

compared nasogastric tube placement rates between TORS and open surgery or TLM. However, one

study reported a statistically significant longer time to oral intake after open surgery when compared to

TORS.(6) When prophylactic placements were excluded, the rate of nasogastric tube placement after

TORS varied widely (0% to 77%) and the mean/ median time to oral intake ranged from 5 to 16 days.

Percutaneous endoscopic gastrostomy (PEG): Sixteen non-comparative and five comparative studies

reported on rates of PEG placement, typically required during adjuvant therapy with RT and/or CRT.(4;6-

8;10;12;13;15-19;21-25;27-30) Rates of initial PEG placement and chronic dependency for recurrent

cases were significantly higher in open surgery when compared to TORS. However, two studies with an

unspecified number of recurrent cases found no statistically significant differences in either rate

between TORS and open surgery.(4;6)There were no significant differences in rates of initial PEG

placement and permanent dependency between TORS and TLM. (30)



Excluding prophylactic placements, TORS had rates of initial PEG that varied widely by disease stage and

anatomical subsite (0% to 46%). Chronic PEG dependency was low across studies (0% to 7%) at follow up

ranging from 1 month to 61 months.

Swallowing function: None of the comparative studies presented data for swallowing function. Four

non-comparative studies examined swallowing function before and after treatment for oropharyngeal

carcinoma with TORS.(17;21;24;25) Measures were based on different questionnaires. One study, which

included 92% of patients with early stages of cancer, reported no differences in swallowing function

before and 6 months to 1 year after surgery.(24) Two studies with 24% to 26% of patients at early stages

reported a significant decline of swallowing function initially with function returning to normal at 1

year.(17;21) The remaining study had only 9% of patients with early stages of cancer and reported

significant decline from baseline to 1 year of follow up (Table 7).(32)

Tracheostomy: Four comparative studies of TORS and open surgery provided data. Excluding one study

having prophylactic tracheostomy for all patients, the number of initial tracheostomies was higher

among patients undergoing open surgery than TORS. However, two studies found no statistically

significant difference in final tube dependency between TORS and open surgery with low rates after 6

months and 20 months of follow up. No statistically significant differences were found for time to

decannulation between TORS and open surgery for patients with advanced tumor stage.(4;6-8) One

study presented data for initial tracheostomy for TLM with only one patient (6%) requiring it. No

significant difference was seen between TORS and TLM.(30)

Overall, initial tracheostomy rates ranged from 0% to 59%, but only a few patients were dependent

(range: 0% to 2%) at last follow up (range: 3 to 51 months). Apart from one study with patients

intubated for an average of 43 days(15), the mean/ median number of days intubated after TORS ranged

from 5 to 10 days.

Speech/ voice function: Table 8 presents information on speech and voice function.



The same measure was used to assess voice function in two studies. A comparative study found no

differences in voice function at 1 year between TORS and open surgery. Further, one non-comparative

study reported no statistically significant deterioration of the voice 6 months and 1 year after TORS

when compared to preoperative measures.(5;24)

Two non-comparative studies presented data on speech function before and after TORS. These studies

used different instruments to assess speech with both showing a statistically significant decline in

function 6 months and 1 year after TORS when compared to preoperative measures. However, patients

still presented with good speech function at 1 year.(17;25) No studies assessed speech or voice function

after TLM.

Health-related quality of life (HRQOL): Table 9 presents the HRQOL outcomes from included studies.

Three non-comparative studies described HRQOL after TORS using different questionnaires.(12;17;25)

One reported a significant decline in satisfaction with eating functions related to dryness of mouth and

difficulty adapting to a change of eating habits at 1 year.(32) However, no statistically significant

differences were reported in overall quality of life preoperatively and 6 months to 1 year after

TORS.(17;25) Further, one study found that most patients regarded their health as “about the same” at

6 months and 1 year after surgery when compared to 1 month before developing cancer.(12) The TORS

procedure does not seem to decrease the quality of patients after the procedure.

There were no studies comparing HRQOL between TORS and open surgery or TLM.

Aesthetic outcomes: Two non-comparative studies measured aesthetic outcomes.(12;25) They found no

statistically significant differences between preoperative and one to two year measurements after the

TORS procedure (Table 9).

Time to return to work/ Recovery time: None of the included studies reported on time to return to work

after TORS.

4. Disease recurrence



Table 10 shows the rates for local, regional and distant recurrence (metastasis). A study with a mean

follow up of 20 months reported one case each of metastasis after TORS and open surgery.(6)

One comparative study assessed loco-regional recurrence and metastasis rates 1 year after TORS and

TLM. There were no statistically significant differences between the groups. (30)

Eight non-comparative studies reported on disease recurrence. (10-13;19;21;23;24) At an average follow

up ranging from 12 to 33 months, the local recurrence rate was 0% to 8% and the regional recurrence

varied from 0% to 12%. The rate of metastasis was low (0% to 4%). All but one study had a high

proportion of patients at an advanced tumor stage.

5. Disease-free survival

Disease-free survival (1 year): Two comparative studies assessed disease-free survival rate at 1

year.(5;30) One study showed a statistically significant higher rate in TORS compared to open surgery

(94% vs 85%, p=0.04). (5) The other reported similar disease-free survival rates at 1 year with TORS

(100%) and TLM (94%).(30)

Both studies along with six non-comparative studies reported disease-free survival rates for TORS at 1

year ranging from 79% to 100%.(10;13;17;23;24;27)

Disease-free survival (2 years): Two studies compared disease-free survival rate at 2 years between

TORS and open surgery. Both reported a higher rate for TORS compared to open surgery, but only one

showed a statistically significant difference. (5;6)

None of the studies assessed disease-free survival 2 years after TLM.

The comparative and three non-comparative studies included in the analysis had some patients with

early stage disease. The studies reported the disease-free survival rate for TORS at 2 years as between

79% and 97%.(5;6;10;11;27)



Disease-free survival (3 years): Disease-free survival rate at 3 years with TORS in three studies ranged

from 83% to 99%. One reported a higher rate compared to open surgery. This difference was statistically

significant.(5;14;18) None of the studies on TLM assessed disease-free survival rate at 3 years.

6. Mortality

Table 11 presents causes of death, mortality rates and survival. One study compared mortality between

TORS and open surgery and two studies compared TORS with TLM. Rates were reported at different

times and none reported statistically significant differences between groups.(6;30;31)

7. Overall Survival – see Table 11

Overall survival (1 year): None of the included studies reported on survival rates 1 year after open

surgery or TLM. One non-comparative study reported overall survival rates for TORS at 1 year as 96%

(range: 91% to 97%) and disease-specific survival as 98% (range: 97% to 100%).(20)

Overall survival (2 years): One comparative study reported overall survival rates 2 years after TORS and

open surgery for recurrent cases of head and neck cancer. TORS was associated with a statistically

significant longer overall survival than open surgery (74% vs 43%, p=0.02).(7) Another study, however,

found no statistically significant differences in survival between TORS and open surgery (100% vs 97%,

p=0.35).(6)

There were no studies reporting survival rates for TLM.

When reported, overall, studies showed that the survival rate 2 years after TORS ranged from 80% to

100% whereas the disease-specific survival varied from 90% to 100%. (6;7;20;25)

Overall survival (3 years): None of the comparative studies reported on survival at 3 years.

One non-comparative study found the 3 year disease-specific survival rate for TORS to be 95% (range:

89% - 98%). (18)

Patient preferences



No data were identified on patient preferences for TORS compared to other surgical options. However,

data collected on HRQOL showed no statistically significant difference before and after patients

underwent TORS.(12;17;32) This suggests that the patients’ quality of life was not negatively impacted

by the procedure.

What matters most to staff

Surgeon’s health: the surgery for head and neck cancer can be challenging for a surgeon as its long

procedure involves: tumor resection, neck dissection and reconstructive surgery in selected cases. No

study compared surgeon’s physical discomfort or symptoms between those performing TORS and other

surgical modalities (open and TLM). Two studies encompassing all modalities, including otolaryngology,

described surgeons’ discomfort associated with robotic surgery. (33;34) Most surgeons (53% to 56%)

experienced physical discomfort attributed to the robotic surgery. However, it was significantly less

frequent when compared to open surgery (75%). Surgeons performing robotic procedures reported

significantly less acute, chronic pain and requirement for further treatment due to serious injuries than

those performing open surgery. Robotic surgery was more likely to be associated with neck, back and

eye problems, while surgeons performing open surgery reported neck, back and knee as the parts more

likely affected.(33;34)

What matters most to the system

Operative time

Table 12 reports on equipment set up times and operative times.

The mean/median equipment set up time was reported in six studies and ranged from 9 to 59 minutes.

One study reported up to 59 minutes for set up time in the first 10 TORS cases. In subsequent cases, this

dropped to an average of 22 minutes.(6;16;24;26;28;29) Three studies compared operative time

between TORS and open surgery. One study defined operative time from induction of anesthesia to

surgical completion, including tumor resection, reconstruction and neck dissection. This study reported



a longer average operative time for open surgery (930min) compared to TORS (900min) but the

difference was not statistically significant.(4) The remaining two studies reported statistically significant

longer times for the open procedure than TORS. In one, operative time was defined as only the time for

tumor resection while the other did not report the definition.(6;7)

One study compared operative time between TORS and TLM (30) and reported no statistically significant

difference in time of transoral resection between procedures.(30)

Seven non-comparative studies reported on the operative time for tumor resection excluding time for

neck dissection. The mean/ median time ranged from 49 minutes to 103 minutes with shorter times

associated with studies with a higher proportion of early stage oropharyngeal carcinoma.

(9;16;19;24;26;28;29) One study reported the average time for neck dissection as 120 minutes and

another reported an average time for tumor resection and neck dissection of 313 minutes for initial

cases and 216 minutes after gaining experience with TORS. (28)

Length of hospital stay – see Table 12

Four comparative studies showed that open surgery was associated with significantly longer

hospitalization (mean/median of 2 to 15 days) than TORS (mean/median of 8 to 20 days).(4;6-8)

Compared to TLM, length of hospital stay was not statistically different for TORS.(30;31) Overall, studies

reported a wide range of length of hospitalization with a higher duration in studies from South Korea

and Canada, while US centers showed shorter stays.

Readmission rate - see Table 12

None of the studies reported on readmission rates after open surgery. One study compared readmission

rates between TORS and TLM and found no statistically significant differences between them (4% vs. 1%,

p=0.33). Overall, studies described readmission rates for TORS as varying between 3% and 15%.5,12,26

Access



TORS has been provided at the University of Alberta Hospital for the past 2 years. To date,

approximately 30 patients have undergone this procedure. The estimated annual provincial demand for

TORS is 40 cases, all of which can be accommodated at the University of Alberta Hospital. Across

Canada, according to the manufacturer, nine centres provide TORS; the other centres are in Ontario (4),

Quebec (3) and British Columbia (1). Calgary patients appear not have access to TORS. TLM is not

available as a routine service in Alberta.

Direct costs

The average per case cost of a TORS procedure in Alberta in 2016 was $94,124 compared to $84,744 for

open surgery. With respect to TORS, this cost included $88,035 in physician fees and inpatient costs,

$3,589 in capital equipment (assuming 200 surgeries of various types are performed with the robot per

year and the lifespan of the robot is 9 years), and $2,500 in disposables associated with the robot. With

respect to open surgery, $84,744 represents inpatient costs and physician fees.

Conclusions

The evidence on TORS, as with many surgical treatments, is of relatively poor quality. There are

insufficient long-term data, data on equipment failure rate and recovery times. There is also a paucity of

high-quality, comparative studies between TORS and nonsurgical interventions (RT and CRT) for

treatment of oropharyngeal carcinoma. With these caveats, some conclusions may be drawn. Overall,

TORS appears as safe and effective as the existing options for oropharyngeal cancer. It shows some

benefits over open surgery in reducing time to oral intake, length of hospital stay, reconstructive surgery

and operative time. In recurrent cases, TORS had lower infection rate, blood loss, positive surgical

margin rates and gastrostomy dependency compared to open surgery. While most outcomes were

comparable in TORS and TLM patients, TLM required more conversions to open surgery than TORS.

Table 2. Inclusion and exclusion criteria of participants. Study Objective Inclusion criteria Exclusion criteria Comments

TORS vs. OPEN

Biron et al. (2017) (4) Canada

To compare TORS and lip-splitting mandibulotomy approach as the primary treatment for advanced stage oropharyngeal squamous cell carcinoma (OPSCC) in patients with planned free flap reconstruction

•OPSCC •Free flap reconstruction

NR •Patients were recruited at different periods

Ford et al. (2014) (5) USA

To investigate oncological survival outcomes and the impact of human papillomavirus (HPV) status for patients treated with TORS versus open surgery

• OPSCC •Refusal to undergo postoperative adjuvant therapy when clearly indicated •Unknown primary carcinoma site •Non-oropharyngeal primary site •Conversion to open surgery (TORS group)

•Data analysts were blinded to patient’s outcome and HPV status when conducting matching analysis

Lee et al. (2014) (6) South Korea

To analyze oncologic and functional outcomes after TORS or conventional surgery through a transoral or mandibulotomy approach

•Age >18 years old •A diagnosis of T1-3 tonsillar squamous cell carcinoma •Indications for surgical treatment

•Contraindications for general anesthesia or surgery •Tumor fixed to the oropharyngeal wall was a contraindication of TORS •Unresectable nodal disease

White et al. (2013) (7) USA

To compare the oncologic and functional outcomes of patients with recurrent OPSCC treated with TORS or open surgery

•Undergone previous treatment for primary OPSCC

•Tumor not amendable to TORS due to: difficult visualization and/or palpation of margins, significant trismus, or base of tongue (BOT) tumors that crossed the midline

•Patients were recruited at different periods

Dean et al. (2010) (8) USA

To evaluate the feasibility of robotic-assisted salvage resection and compare it with open.

•Age >19 years old •Primary or recurrent T1-2 oropharyngeal carcinoma

•T3-4 carcinoma •Mouth opening <1.5cm •Tumor invading bone •Tumor resection was predicted to result in a through and through defect necessitating free tissue transfer

•Patients were recruited at different periods

TORS vs. TLM

Zevallos et al. (2016) (31) USA

To describe the utilization and short-term outcomes among patients undergoing TORS and TLM for OPSCC

•Pathologically confirmed OPSCC •Clinical cancer stage IVB •Prior malignancy •Distant metastasis •Nononcologic excision alone •Nonsurgical approach as the primary treatment

•No further details on TLM group.




•Open surgery •Outpatient surgery •Unknown surgical status, cancer stage or margin status

Sumer et al. (2013) (30) USA

To compare functional and perioperative outcomes between TORS and transoral laser microsurgery (TLM)

•Age >18 years old •Previously untreated OPSCC

•Prior head and neck aerodigestive tract malignancy •Use of open approach to facilitate the transoral access to the tumor •Distant metastasis at presentation •Tumor stage T4a (except in cases of unilateral deep/extrinsic tongue muscle involvement) and T4b •Unresectable nodal disease

NON-COMPARATIVE STUDIES

Albergotti et al. (2017) (9) USA

To assess learning curves for the oncologic TORS surgeon and to identify the number of cases needed to identify the learning phase

•OPSCC •Non-oropharyngeal primary site •Non-malignant abnormality •Unknown primary tumor •No tumor in the main oropharyngeal specimen •Surgery requiring free flap reconstruction •Inability to define margin status in the diagnostic procedure

Albergotti et al. (2017b) (22) USA

To describe short-term swallowing related outcomes after TORS for OPSCC

•OPSCC •History of previous TORS •Non-malignant abnormality •Non-oropharyngeal primary site •Tracheotomy procedure in the perioperative period •Contraindication to swallowing evaluation •Patients with less than 2 year follow up data

Rubek et al (2017) (23) Denmark

To demonstrate feasibility of TORS and concurrent neck dissection for treatment of early stage of OPSCC

•Tumor T1-2 and N0-1 •Stage I-III biopsy verified OPSCC •Confirmation from MRI that it was possible to achieve a free margin ≥2mm, excluding bone involvement or internal carotid artery

•Age<18 years old •Previous head and neck cancer •Previous radiotherapy in the head and neck region •WHO performance status >2 •Inability to attend follow up consultations •Substantial co-morbidity

•Study only included cases likely to achieve negative margins




Funk et al (2016) (10) USA

To determine whether intermediate to high risk features identified in the pre-HPV era also predict relapse risk in HPV-positive patients

•OPSCC •HPV positive tumors •Patients with indication for adjuvant treatment but did not receive further therapy

•History of surgery or radiotherapy (RT) for head and neck carcinoma •Patients who were lost to follow up immediately after surgery

Kaczmar et al (2016) (11) USA

To determine the clinical factors predicting recurrence in patients with HPV-positive oropharyngeal cancer treated with TORS and adjuvant therapy when indicated

•Pathologically confirmed OPSCC •p16 positive patients

NR

Choby et al. (2015) (12) USA

To report quality of life outcomes of patients with OPSCC who received only TORS

•OPSCC •Adjuvant therapy with RT or CRT •Unknown primary tumor •Unknown primary carcinoma site •Non-oropharyngeal primary site

Lorincz et al. (2015) (13) Germany

To evaluate feasibility and functional outcomes for OPSCC treated with TORS

•OPSCC •TORS was the primary treatment modality

NR

Mercante et al. (2015) (24) Italy

To describe the one year follow up quality of life and to evaluate swallowing and voice function of patients with BOT tumors treated with TORS alone

•BOT tumor T1-2 •Tumor amendable to transoral radical ‘en bloc’ resection •Tumor with superficial extension or infiltration into the intrinsic muscle <3cm

•Infiltration of the extrinsic muscle by tumor (cT4) •Mouth opening ≤2.5cm •Distant metastasis •Previous treatment for head and neck tumor •Adverse features that would require adjuvant treatment: positive or close (<5mm) margins; ≥2 metastatic lymph nodes; nodal extracapsular extension

•Study only includes patients who did not undergo adjuvant therapy

Lukens et al. (2014) (14) USA

To describe frequency of soft tissue necrosis after TORS and adjuvant RT in patients with oropharyngeal carcinoma

•OPSCC treated with TORS followed by RT (with or without chemotherapy) •>6 months of follow up

•Previous head and neck RT •Insufficient clinical follow up •Procedures converted to open surgery with flap reconstruction

Al-Khudari et al. (2013) (15) USA

To assess factors that influence gastrostomy tube use after TORS for oropharyngeal cancer

•Pathologically confirmed squamous cell carcinoma •Tonsil or BOT tumors

•Oral tongue, nasopharynx, supraglottis, and hypopharynx tumor

Dziegielewski et al. (2013) (32) USA

To describe short and long-term health-related quality of life (HRQOL) and functional outcomes in patients with OPSCC undergoing TORS

•Biopsy-proven OPSCC •cT1-3 tumors •Scheduled for TORS

•Inadequate transoral exposure to allow for TORS instrumentation •Inability to complete the Head and Neck Cancer Inventory (HNCI) •Distant metastasis




•Unresectable primary tumor •Synchronous second primary tumor


To demonstrate feasibility, efficacy and functional outcomes of TORS as a treatment for T1-2 BOT tumors.

•BOT tumor T1-2 •Tumor amendable to transoral radical ‘en bloc’ resection •Tumor with superficial extension or infiltration into the intrinsic muscle <3cm

•Infiltration of the extrinsic muscle by tumor (cT4) •Mouth opening ≤2.5cm •Distant metastasis

Park et al. (2013) (16) South Korea

To assess 2-year oncological and functional outcomes of patients undergoing TORS as a treatment for oropharyngeal cancer

•Age> 18 years old •Diagnosis of oropharyngeal cancer

•Contraindications to general anesthesia and operation •Small retrognathic mandible or poor mouth opening •Unresectable nodal disease •Distant metastasis •Invasion of parapharyngeal space

Leonhardt et al. (2012) (17) USA

To assess 1 year HRQOL and functional outcomes of patients undergoing TORS for oropharyngeal cell carcinoma

•OPSCC NR •Patients and the HRQOL assessor were blinded to prior scores to minimize bias

Moore et al (2012) (18) USA

To examine the long-term oncological and functional outcomes of TORS alone or combined with adjuvant therapy as a treatment for OPSCC

•Normal oral compliance •Medical clearance for anesthesia •Tumor estimated to be completely resectable with TORS •Minimum 2 years follow up

•Recurrent disease •Primary RT or chemotherapy •Poor candidates for TORS: submucosal tumors; mandible or hyoid involvement; extension into the deep tongue musculature, mandible, hyoid, skull base, prevertebral fascia, or pterygoid musculature; extensive involvement of the great vessels; lateral extension into the soft tissues of the neck

•Study only includes patients with tumors deemed resectable

Weinstein et al. (2012) (19) USA

To assess safety and efficacy of TORS and neck dissection without postoperative adjuvant therapy as treatment for OPSCC

•Age >18 years old •Indication for diagnostic or therapeutic transoral approaches to oral cavity, oropharynx or larynx •Previously untreated, biopsy-proven OPSCC of stage I to IVB

•Unexplained fever and/ or untreated, active infection •Pregnancy •Previous head and neck surgery •Contraindications to general anesthesia or transoral surgical approaches

Cohen et al. (2011) (20) USA

To assess the differences in outcomes of HPV positive and

• Age >18 years old •Indication for diagnostic or

•Unexplained fever and/ or untreated, active infection




negative patients undergoing TORS for oropharyngeal carcinoma

therapeutic transoral approaches to oral cavity, oropharynx or larynx •Untreated biopsy-proven squamous cell carcinoma

•Pregnancy •Contraindications to general anesthesia or transoral surgical approaches •TORS contraindications: AJCC stage inferior vena cava lesions; T4b lesions; oropharyngeal lesions extending to the midline of the posterior pharyngeal wall; deep tongue musculature involvement greater than 50%; prevertebral muscle involvement •Unresectable nodal metastasis

Sinclair et al. (2011) (21) USA

To evaluate functional outcomes before and after patients underwent TORS for early oropharyngeal carcinoma

•Primary T1-2 OPSCC •Prior non-robotic surgical resection or RT •Inadequate postoperative functional follow up data


To determine the oncological and functional outcomes in patients with advanced oropharyngeal carcinoma undergoing TORS followed by adjuvant therapy as indicated

• Age >18 years old •Indication for diagnostic or therapeutic transoral approaches to oral cavity, oropharynx or larynx •Previously untreated OPSCC •Stages III, IVA and IVB disease

•Unexplained fever and/ or untreated, active infection •Pregnancy •Previous head and neck surgery •Contraindications to general anesthesia or transoral surgical approaches •Stage IVC, except for a curable distant metastasis •Unresectable nodal metastasis •Tumor stage T4a (except in cases of unilateral deep/extrinsic tongue muscle involvement) and T4b •Any T disease with invasion of deep tissues lateral to the constrictor muscle or posterior invasion of the prevertebral fascia


To investigate the feasibility of TORS as treatment for OPSCC

• Age >18 years old •Untreated neoplasm of the head and neck with indications for diagnosis and management of the tumor

•Pregnancy •Being unable to comprehend the goals of treatment and express desire to proceed with treatment •Poor candidates for general anesthesia and surgical therapy




•Previous treatment of head and neck cancer •Anatomical conditions leading to poor transoral exposure and visualization of tumor: fixation of the tumor to the lateral or posterior pharyngeal wall, indicating deep invasion into the parapharyngeal space; intimate association with the carotid artery, internal jugular vein, or prevertebral fascia; skull base invasion, mandibular invasion, or clinically significant trismus, indicating invasion of the pterygoid musculature


To describe feasibility of TORS radical tonsillectomy

• Age >18 years old •Indication for diagnostic or therapeutic transoral approaches to oral cavity, oropharynx or larynx

•Unexplained fever and/ or untreated, active infection •Pregnancy •Previous head and neck surgery •Contraindications to general anesthesia or transoral surgical approaches •Inadequate visualization for transoral surgery •Unresectable lymph nodes •TORS contraindications: deep tongue musculature involvement greater than 50%; mandibular invasion; pharyngeal wall involvement necessitating resection of more than 50% of the posterior pharyngeal wall; carotid artery involvement; fixation of tumor to the prevertebral fascia

BOT= Base of Tongue; HNCI= Head and Neck Cancer Inventory; HPV= Human Papillomavirus; HRQOL= Health-related Quality of Life; NR= Not Reported; OPSCC= Oropharyngeal Squamous Cell Carcinoma; RT= Radiotherapy; TORS= Transoral Robotic Surgery; TLM= Transoral Laser Microsurgery; WHO= World Health Organization



Table 3. Characteristics of Participants.

Study Sample size

Age in years Median (Range)

Mean ± SD Gender

n (%Male) Smoking status

n (%) HPV status

n (% Positive)

Prior HNC treatment/

recurrent case n (%)

Anatomical subsites

n (%)

Extracapsular spread n (%)

T stage n (%)

N stage n (%)

Overall stage n (%)

TORS vs. OPEN


TORS: 18 OPEN: 29

TORS: 60±NR OPEN: 58±NR P=0.69

TORS: 12 (67) OPEN: 23 (79) P=0.31

TORS: - > 10 pack years: 10 (56) - ≤ 10 pack years: 8 (44) OPEN: - > 10 pack years: 17 (59) - ≤ 10 pack years: 12 (41) P=0.67

TORS: NR - p16: 16 (89) OPEN: NR - p16: 25 (86) P=0.61

TORS: NR OPEN: NR

TORS: - BOT: 5 (28) - Tonsil: 13 (72) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) OPEN: - BOT: 13 (45) - Tonsil: 16 (55) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) P=0.36

TORS: NR OPEN: NR

TORS: - pT1: 5 (28) - pT2: 10 (56) - pT3: 3 (17) - pT4: 0 (0) OPEN: - pT1: 7 (24) - pT2: 17 (59) - pT3: 5 (17) - pT4: 0 (0) P=0.96

TORS: - pN0: 1 (6) - pN1: 1 (6) - pN2: 13 (72) - pN3: 3 (17) OPEN: - pN0: 1 (3) - pN1: 3 (10) - pN2: 23 (79) - pN3: 2 (7) P=0.68

TORS: - I-II: 0 (0) - III-IV: 18 (100) OPEN: - I-II: 0 (0) - III-IV: 29 (100) P=NA


TORS: 65 OPEN: 65

TORS: 59±11 OPEN: 58±10 P=0.98

TORS: 52 (80) OPEN: 51 (78) P=0.76

TORS: - Former smoker (n=62): 41 (63)[66] - Current smoker (n=60): 21 (32)[35] OPEN: - Former smoker (n=53): 34 (52) [64] - Current smoker (n=51): 19 (29) [37] Pformer= 0.08 Pcurrent=0.18

TORS: - p16 (n=63): 51 (78) [81] OPEN: - p16 (n=56): 44 (68) [79] P=0.29

TORS: NR OPEN: NR

TORS: - BOT: 21 (32) - Tonsil: 38 (58) - Soft palate: 0 (0) - Pharyngeal wall: 6 (9) OPEN: - BOT: 9 (14) - Tonsil: 43 (66) - Soft palate: 1 (2) - Pharyngeal wall: 12 (18) P<0.01

TORS (n=48): 28 (43)[58] OPEN (n=47): 26 (40)[55] P=0.65

TORS: - pT1: 21 (32) - pT2: 36 (55) - pT3: 6 (9) - pT4: 2 (3) OPEN: - pT1: 21 (32) - pT2: 36 (55) - pT3: 6 (9) - pT4: 2 (3) P>0.99

TORS: - pN0: 14 (22) - pN1: 8 (12) - pN2: 42 (65) - pN3: 1 (2) OPEN: - pN0: 14 (22) - pN1: 13 (20) - pN2: 36 (55) - pN3: 2 (3) P=0.23

TORS: - I: 4 (6) - II: 10 (15) - III: 7 (11) - IV: 44 (68) OPEN: - I: 4 (6) - II: 10 (15) - III: 12 (18) - IV: 39 (60) P=0.26


TORS: 27 OPEN: 30

TORS: 58±9 OPEN:

TORS: 21 (78) OPEN: 25 (83)

TORS: NR OPEN: NR

TORS: 18 (67) OPEN: 21 (70)

TORS: NR OPEN: NR

TORS: - BOT: 0 (0) - Tonsil: 27 (100)

TORS: 3 (11) OPEN: 2 (7)

TORS: - pT1: 10 (37) - pT2: 12 (44)

TORS: NR OPEN: NR

TORS: - I: 2 (7) - II: 4 (15)




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

- mandibulotomy: 61±8 - TOS: 56±9 P=0.18

- mandibulotomy: 12 (86) - TOS: 13 (81) P=0.91


- Soft palate: 0 (0) - Pharyngeal wall: 0 (0) OPEN: - BOT: 0 (0) - Tonsil: 30 (100) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) - Mandibulotomy: - BOT: 0 (0) - Tonsil: 14 (100) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) - TOS: - BOT: 0 (0) - Tonsil: 16 (100) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) P=NA


- pT3: 5 (19) - pT4: 0 (0) OPEN: - pT1: 6 (20) - pT2: 20 (67) - pT3: 4 (13) - pT4: 0 (0) - Mandibulotomy: - pT1: 0 (0) - pT2: 11 (79) - pT3: 3 (21) - pT4: 0 (0) - TOS: - pT1: 6 (38) - pT2: 9 (56) - pT3: 1 (6) - pT4: 0 (0) P=0.04

- III: 1 (4) - IV: 20 (74) OPEN: - I: 0 (0) - II: 5 (17) - III: 2 (7) - IV: 23 (77) - Mandibulotomy: - I: 0 (0) - II: 2 (14) - III: 2 (14) - IV: 10 (71) - TOS: - I: 0 (0) - II: 3 (19) - III: 0 (0) - IV: 13 (81) P=0.68


TORS: 64 OPEN: 64

TORS: 61±NR OPEN: 61±NR P=NA

TORS: 48 (75) OPEN: 53 (83) P=NA

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: 64 (100) - RT: 62 (97) - CRT: 37 (58) - Surgery: 12 (19) OPEN: 64 (100) - RT: 45 (70) - CRT: 22 (34) - Surgery: 44 (69)

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS‡: - T1: 25 (39) - T2: 34 (53) - T3: 2 (3) - T4: 3 (5) OPEN‡: - T1: 23 (36) - T2: 29 (45) - T3: 9 (14) - T4: 3 (5)

TORS‡: - N0: 37 (58) - N1:7 (11) - N2a: 0 (0) - N2b: 17 (27) - N2c: 2 (3) - N3: 1 (2) OPEN‡: - N0: 34 (53)

TORS: - I: 21 (33) - II: 10 (16) - III: 9 (14) - IV: 24 (38) OPEN: - I: 15 (23) - II: 11 (17) - III: 13 (20) - IV: 25 (39)




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

PRT<0.001 PCT=0.01 Psurgery<0.001

P=NA

- N1: 16 (25) - N2a: 0 (0) - N2b: 8 (13) - N2c: 6 (9) - N3: 0 (0) P=NA

P=NR


TORS: 22 OPEN: 14

TORS: - Primary cases: 56±12 - Recurrent cases: 68±5 OPEN: - Recurrent cases: 59±11 P=0.07

TORS: 19 (86) - Primary cases: 13 (87) - Recurrent cases: 6 (86) OPEN: - Recurrent cases: 12 (86) P=0.99

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: 7 (32) - RT: 2 (9) - CRT: 2 (9) - Surgery: 0 (0) - Surgery + RT: 1 (14) - Surgery + CRT: 2 (28) OPEN: 14 (100) - RT: 6 (43) - CRT: 4 (29) - Surgery: 1 (7) - Surgery + RT: 3 (21) - Surgery + CRT: 0 (0) P=NR

TORS: - BOT: 9 (41) - Tonsil: 8 (36) - Soft palate: 1 (5) - Pharyngeal wall: 4 (18) - Primary cases: - BOT: 4 (27) - Tonsil: 8 (53) - Soft palate: 0 (0) - Pharyngeal wall: 3 (20) - Recurrent cases: - BOT: 5 (71) - Tonsil: 0 (0) - Soft palate: 1 (14) - Pharyngeal wall: 1 (14) OPEN: - Recurrent cases: - BOT: 5 (36) - Tonsil: 5 (36) - Soft palate: 4 (29) - Pharyngeal wall: 0 (0)

TORS: NR OPEN: NR

TORS‡: - T1: 10 (45) - T2: 12 (55) - T3: 0 (0) - T4: 0 (0) - Primary cases: - T1: 6 (40) - T2: 9 (60) - T3: 0 (0) - T4: 0 (0) - Recurrent cases: - T1: 4 (57) - T2: 3 (43) - T3: 0 (0) - T4: 0 (0) OPEN‡: - Recurrent cases: - T1: 3 (21) - T2: 11 (79) - T3: 0 (0) - T4: 0 (0) P=0.25

TORS: NR OPEN: NR

TORS: - I: 4 (18) - II: 8 (36) - III: 4 (18) - IV: 6 (27) - Primary cases: - I: 0 (0) - II: 6 (40) - III: 3 (20) - IV: 6 (40) - Recurrent cases: - I: 4 (57) - II: 2 (28) - III: 1 (14) - IV: 0 (0) OPEN: - Recurrent cases: - I: 0 (0) - II: 8 (57) - III: 1 (7) - IV: 5 (36) P=0.002




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

P=0.04

TORS vs. TLM


TORS: 369 TLM: 145

TORS: 58±10 TLM: 58±10 P=0.97

TORS: 316 (86) TLM: 119 (82) P=0.31

TORS: NR TOS: NR

TORS (n=251): 213 (58) [85] TLM (n=69)= 55 (38) [80] P<0.001

TORS: 0 (0) TOS: 0 (0) P=NA

TORS: - BOT: 101 (27) - Tonsil: 254 (69) - Soft palate/ pharyngeal wall: 14 (4) TLM: - BOT: 24 (17) - Tonsil: 110 (76) - Soft palate/ pharyngeal wall: 11 (8) P=0.01

TORS: NR TLM: NR

TORS: - cT1: 159 (43) - cT2: 168 (46) - cT3: 33 (9) - cT4a: 9 (2) TLM: - cT1: 61 (42) - cT2: 67 (46) - cT3: 13 (9) - cT4a: 4 (3) P=0.99

TORS: - cN0: 76 (21) - cN1: 89 (24) - cN2: 202 (55) - cN3: 0 (0) - cNx: 2 (1) TLM: - cN0: 32 (22) - cN1: 36 (25) - cN2: 77 (53) - cN3: 0 (0) - cNx: 0 (0) P=0.81

TORS: NR TLM: NR


TORS: 17 TLM: 16

Overall: 57±NR TORS: 14 (82) TLM: 14 (88) P=1.00

TORS: - >10 pack years: 5 (29) - ≤ 10 pack years: 2 (12) - None: 10 (59) TLM: - >10 pack years: 8 (50) - ≤ 10 pack years: 3 (19) - None: 5 (31) P=0.27

TORS: NR TLM: NR

TORS: 0 (0) TLM: 0 (0) P=NA

TORS: - BOT: 10 (59) - Tonsil: 7 (41) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) TLM: - BOT: 10 (63) - Tonsil: 6 (38) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) P=1.00

TORS: NR TLM: NR

TORS: - pT1: 10 (59) - pT2: 5 (29) - pT3: 2 (12) - pT4: 0 (0) TLM: - pT1: 5 (31) - pT2: 7 (44) - pT3: 3 (19) - pT4: 1 (6) P=0.35

TORS: NR TLM: NR

TORS: - I: 1 (6) - II: 1 (6) - III: 5 (29) - IV: 10 (59) TLM: - I: 0 (0) - II: 0 (0) - III: 1 (6) - IV: 15 (94) P=0.08


Albergotti et al. (2017) (9)

TORS: 160 TORS: 59±10 TORS: 125 (78) TORS: NR TORS: - p16: 126 (79)

TORS: 13 (8) - CRT: 13 (8)

TORS: - BOT: 58 (36)

TORS: NR TORS‡: - T1: 63 (39)

TORS‡: - N0: 35 (22)

TORS: NR




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

USA - Tonsil: 92 (58) - Other: 10 (6)

- T2: 77 (48) - T3:17 (11) - T4 1 (1) - Tx: 2 (1)

- N1: 34 (21) - N2: 79 (49) - N3: 3 (2) - Nx: 9 (6)


TORS: 51 TORS: 57±8 TORS: 41 (80) TORS: - Current smoker: 13 (25) - Former smoker: 14 (27) - Never: 24 (47)

HPV: - p16: 50 (98)

TORS: - RT: 3 (6) - Surgery: 6 (12)

TORS: - BOT: 21 (41) - Tonsil: 30 (59) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0)

TORS: NR TORS‡: - T1: 24 (47) - T2: 20 (39) - T3: 3 (6) - Tx: 4 (8)

TORS‡: - N0: 7 (14) - N1: 5 (10) - N2a: 11 (22) - N2b: 24 (47) - N2c: 3 (6) - N3: 1 (2)

TORS: NR


TORS: 30 TORS: 62 (42-74)

TORS: 18 (60) TORS: - > 10 pack years: 17 (57) - ≤ 10 pack years: 2 (7) - None: 11 (37)

TORS: 26 (87) - p16: 27 (90)

TORS: 0 (0) TORS: - BOT: 7 (23) - Tonsil: 21 (70) - Soft palate: 0 (0) - Pharyngeal wall: 2 (7)

TORS: 6 (20) TORS: - cT1: 13 (43) - cT2: 17 (57) - cT3: 0 (0) - cT4: 0 (0) - pT1: 14 (47) - pT2: 16 (53) - pT3: 0 (0) - pT4: 0 (0)

TORS: - cN0: 16 (53) - cN1: 14 (47) - cN2a: 0 (0) - cN2b: 0 (0) - cN2c: 0 (0) - cN3: 0 (0) - pN0: 12 (40) - pN1: 10 (33) - pN2a: 1 (3) - pN2b: 7 (23) - pN2c: 0 (0) - pN3: 0 (0)

TORS: - I-III: 30 (100) - IV: 0 (0)


TORS: 25 TORS: 58 (39-81)

TORS: NR TORS: - ≥10 pack years: 8 (32) - <10 pack years: 2 (8) - None: 15 (60)

TORS: - p16: 25 (100)


TORS: 7 (28) TORS: - pT1: 4 (16) - pT2: 14 (56) - pT3: 6 (24) - pT4: 1 (4)

TORS: - pN0: 4 (16) - pN1: 4 (16) - pN2a: 9 (36) - pN2b: 8 (32)

TORS: - I: 0 (0) - II: 1 (4) - III: 7 (28) - IV: 17 (68)




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

- pN2c: 0 (0) - pN3: 0 (0)


TORS: 114 TORS: 57 (41-91)

TORS: 107 (93.9) TORS (N=110): - >10 pack years: 35 (31)[32] - ≤10 pack years: 75 (66)[68]

TORS: - p16: 114 (100)

TORS: NR TORS: - BOT: 43 (38) - Tonsil: 65 (57) - other subsites: 6 (5)

TORS: 38 (33) TORS (n=113): - pT1-2: 103 (90)[91] - pT3: 7 (6)[6] - pT4: 3 (3)[3]

TORS: - pN0-2a: 42 (37) - pN2b-3: 72 (63)

TORS: - I-III: 28 (25) - IV: 86 (75)


TORS: 34 TORS: 59±8 TORS: 26 (76.5) TORS: - Smoker: 24 (71) - Non-smoker: 10 (29)

TORS: - p16 (n=33): 25 (74) [76]

TORS: NR TORS: - BOT: 15 (44) - Tonsil: 16 (47) - Soft palate: 2 (6) - Pharyngeal wall: 1 (3)

TORS (n=19): 4 (12)[21]

TORS‡: - T1: 20 (59) - T2: 13 (38) - T3: 1 (3)

TORS‡: - N0: 13 (38) - N1: 16 (47) - N2a: 3 (9) - N2b: 2 (6)

TORS: NR


TORS: 35 TORS: 65 (49-84)

TORS: 26 (74) TORS: - <10 pack years and no alcohol consumption on a regular basis: 9 (26)

TORS: 12 (34) - p16: 18 (51)

TORS: NR TORS: - BOT: 14 (40) - Tonsillolingual: 5 (14) - Tonsil: 13 (37) - Soft palate: 3 (9) - Pharyngeal wall: 0 (0)

TORS: NR TORS: - cT1: 19 (5) - cT2: 16 (46) - cT3-4: 0 (0) - pT1: 19 (54) - pT2: 15 (43) - pT3-4: 1 (3)

TORS: - pN0: 13 (37) - pN1: 8 (23) - pN2: 13 (37) - pN3: 1 (3)

TORS: - I-II: 13 (37) - III-IV: 22 (63)


TORS: 13 TORS: 56±10 TORS: 7 (54) TORS: NR TORS: NR TORS: 0 (0) TORS: - BOT: 13 (100) - Tonsil: 0 (0) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0)

TORS: 0 (0) TORS: - pT1: 10 (77) - pT2: 3 (24) - pT3: 0 (0) - pT4: 0 (0)

TORS: - pN0: 12 (92) - pN1: 0 (0) - pN2a: 0 (0) - pN2b: 0 (0) - pN2c: 1 (8) - pN3: 0 (0)

TORS: - I: 10 (77) - II: 2 (15) - III: 0 (0) - IV: 1 (8)


TORS: 170 TORS: 57 (41-87)

TORS: 153 (90) TORS (n=168): - Current smoker: 5 (3) [3] - Former smoker: 98 (58) [58] - Never: 65 (38) [39]

TORS: NR TORS: 0 (0) TORS: - BOT: 66 (39) - Tonsil: 104 (61) - Soft palate: (0) - Pharyngeal wall: 0 (0)

TORS: 16 (9) TORS (n=169): - pT1: 60 (35) [36] - pT2: 85 (51) [51] - pT3: 20 (12) [12] - pT4a: 3 (2) [2]

TORS: NR TORS: NR




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

- pT4b: 0 (0) [0]


TORS: 29 TORS: 60.2 (46-83)††

TORS: 24 (83) - Primary cases: 18 (82) - Recurrent cases: 6 (86)

TORS: NR TORS: NR TORS: 7 (24) - RT: 1 (4) - CRT: 5 (17) - Surgery + CRT: 1 (3)

TORS: - BOT: 13 (45) - Tonsil: 16 (55) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) - Primary cases: - BOT: 8 (36) - Tonsil: 14 (64) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0) - Recurrent cases: - BOT: 5 (71) - Tonsil: 2 (29) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0)

TORS: NR TORS‡: - T1: 7 (24) - T2: 14 (48) - T3: 5 (17) - T4: 3 (10) - Primary cases‡: - T1-2: 17 (77) - T3-4: 5 (23) - Recurrent cases‡: - T1-2: 4 (57) - T3-4: 3 (43)

TORS: NR TORS: NR

Dziegielewski et al. (2013)(32) USA

TORS: 81 TORS: 58 (39-81)††

TORS: 65 (80) TORS: - Smoker: 62 (77) - Non-smoker: 19 (23)

TORS (n=71): 51 (63)[72] - p16 (n=71): 60 (74)[85]

TORS: 2 (2) - CRT: 2 (2)


TORS: NR TORS: - pT1: 34 (42) - pT2: 39 (48) - pT3: 6 (7) - pT4: 2 (2)

TORS: - pN0: 9 (11) - pN1: 9 (11) - pN2a: 21 (26) - pN2b: 31 (38) - pN2c: 3 (4) - pN3: 6 (7) - pNx: 2 (2)

TORS (n=79): - I: 7 (9) [9] - II: 0 (0) [0] - III: 9 (11) [11] - IV: 63 (78)[80]


TORS: 13 TORS: 61±10 TORS: 9 (69) TORS: NR TORS: NR TORS: 3 (23) - RT: 1 (8) - CRT: 1 (8) - Surgery: 1 (8)


TORS: NR TORS: - cT1: 8 (62) - cT2: 5 (38) - cT3: 0 (0) - cT4: 0 (0)

TORS: - cN0: 7 (54) - cN1: 1 (8) - cN2a: 0 (0) - cN2b: 4 (31) - cN2c: 1 (8)

TORS: - I: 7 (54) - II: 1 (8) - III: 1 (8) - IV: 4 (31)




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

- pT1: 9 (69) - pT2:4 (31) - pT3: 0 (0) - pT4: 0 (0)

- cN3: 0 (0) - pN0: 8 (62) - pN1: 1 (8) - pN2a: 0 (0) - pN2b: 4 (31) - pN2c: 0 (0) - pN3: 0 (0)


TORS: 39 TORS: 57 (34-77)††

TORS: 28 (72) TORS: NR TORS: NR TORS: NR TORS: - BOT: 9 (23) - Tonsil: 28 (72) - Soft palate: 2 (5) - Pharyngeal wall: 0 (0)

TORS: NR TORS‡: - T1: 14 (36) - T2: 20 (51) - T3: 3 (8) - T4: 2 (5)

TORS‡: - N0: 13 (33) - N1: 3 (8) - N2a: 1 (3) - N2b: 20 (51) - N2c: 2 (5) - N3: 0 (0)

TORS: - I: 4 (10) - II: 9 (23) - III: 3 (8) - IV: 23 (59)


TORS: 38 TORS: 57 (41-86)††

TORS: 28 (74) TORS: - Smoker: 21 (55) - Non-smoker: 17 (45)

TORS: NR TORS: - RT: 2 (5) - CRT: 1 (3)

TORS: NR TORS: NR TORS: - pT1: 12 (32) - pT2: 21 (55) - pT3: 3 (8) - pT4: 2 (5)

TORS: - pN0: 10 (26) - pN1: 13 (34) - pN2a: 1 (3) - pN2b: 14 (37) - pN3: 0 (0)

TORS: - I: 3 (8) - II: 7 (18) - III: 14 (37) - IVA: 14 (37)


TORS: 66 TORS: 55.2 (36-80)††

TORS: 59 (89) TORS: - Current smoker: 17 (26) - Former smoker: 16 (24) - Never: 33 (50)

TORS: 49 (74) - p16 (n=65): 58 (88) [89]


TORS: 37 (56) TORS (n=64): - pT1: 22 (33) [34] - pT2: 30 (45) [47] - pT3: 3 (5) [5] - pT4a: 9 (14) [14] - pT4b: 0 (0) [0]


TORS: - I: 3 (5) - II: 5 (8) - III: 7 (11) - IVA: 43 (65) - IVB: 8 (12)

Weinstein et al. (2012)

TORS: 30 TORS: 59 (44-75)††

TORS: 21 (70) TORS (n=28): - Current smoker: 8

TORS: NR TORS: 0 (0) TORS: - BOT: 9 (30)

TORS: 2 (7) TORS: - cT1: 9 (30)

TORS: - cN0: 15 (50)

TORS: - I: 5 (17)




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

(19) USA

(27) [29] - Former smoker: 17 (57) [61] - Never: 3 (10) [10]

- Tonsillolingual: 3 (10) - Tonsil: 14 (47) - Soft palate: 3 (10) - Pharyngeal wall: 1 (3)

- cT2: 16 (53) - cT3: 4 (13) - cT4: 1 (3)

- cN1: 10 (33) - cN2a: 1 (3) - cN2b: 4 (13) - cN2c: 0 (0) - cN3: 0 (0)

- II: 9 (30) - III: 10 (33) - IV: 6 (20)


TORS: 50 TORS: - HPV+: 75 (37-77)†† - HPV-: 63 (49-74)††

TORS: 47 (94) - HPV+: 35 (95) - HPV-: 12 (92)

TORS: NR TORS: 37 (74) - p16: 34 (68)

TORS: 0 (0) - HPV+: 0 (0) - HPV-: 0 (0)

TORS: - BOT: 24 (48) - Tonsil: 23 (46) - Soft palate: 2 (4) - Pharyngeal wall: 1 (2) - HPV+: - BOT: 17 (46) - Tonsil: 19 (52) - Soft palate: 0 (0) - Pharyngeal wall: 1 (3) - HPV-: - BOT: 7 (54) - Tonsil: 4 (31) - Soft palate: 2 (15) - Pharyngeal wall: 0 (0)

TORS (n=48): 19 (38)[40] - HPV+ (n=36): 16 (43)[44] - HPV- (n=12): 3 (23) [25]

TORS‡: - T1: 15 (30) - T2: 24 (48) - T3: 8 (16) - T4a: 3 (6) - T4b: 0 (0) - HPV+‡: - T1: 10 (27) - T2: 18 (49) - T3: 8 (22) - T4a: 1 (3) - T4b: 0 (0) - HPV-‡: - T1: 5 (39) - T2: 6 (46) - T3: 0 (0) - T4a: 2 (15) - T4b: 0 (0)

TORS‡: - N0: 9 (18) - N1: 21 (42) - N2a: 0 (0) - N2b: 20 (40) - N2c: 0 (0) - N3: 0 (0) - HPV+‡: - N0: 5 (13) - N1: 14 (38) - N2a: 0 (0) - N2b: 18 (49) - N2c: 0 (0) - N3: 0 (0) - HPV-‡: - N0: 4 (31) - N1: 7 (54) - N2a: 0 (0) - N2b: 2 (15) - N2c: 0 (0) - N3: 0 (0)

TORS: - I: 3 (6) - II: 4 (8) - III: 20 (40) - IV: 23 (46) - HPV+: - I: 2 (5) - II: 2 (5) - III: 14 (38) - IV: 19 (51) - HPV-: - I: 1 (8) - II: 2 (15) - III: 6 (46) - IV: 4 (31)


TORS: 42 TORS: 55±NR TORS: 29 (69) TORS: NR TORS: NR TORS: 0 (0) TORS: - BOT: 13 (31) - Tonsil: 29 (69) - Soft palate: 0 (0)

TORS: NR TORS‡: - T1: 19 (45) - T2: 23 (55) - T3: 0 (0)

TORS‡: - N0: 10 (24) - N1: 5 (12) - N2: 27 (64)

TORS: - I: 3 (7) - II: 7 (17) - III: 32 (76)




Study Sample size


Mean ± SD Gender


n (%) HPV status

n (% Positive)



Anatomical subsites

n (%)


T stage n (%)

N stage n (%)

Overall stage n (%)

- Pharyngeal wall: 0 (0)

- T4: 0 (0) - N3: 0 (0) - IV: 0 (0)


TORS: 47 TORS: 57 (37-77)††

TORS: 43 (91) TORS: NR TORS: NR TORS: 0 (0) TORS: - BOT: 23 (49) - Tonsil: 23 (49) - Soft palate: 1 (2) - Pharyngeal wall: 0 (0)

TORS: 19 (40) TORS‡: - T1: 13 (28) - T2: 23 (49) - T3: 9 (19) - T4: 2 (4)

TORS‡: - N0: 1 (2) - N1: 24 (51) - N2a: 1 (2) - N2b: 19 (40) - N2c: 2 (4) - N3: 0 (0)

TORS: - I-II: 0 (0) - III: 24 (51) - IV: 23 (49)


TORS: 45 TORS: 57 (38-88)††

TORS: 40 (89) TORS: - Never: 30 (67)

TORS: NR TORS: 0 (0) TORS: - BOT: 26 (58) - Tonsil: 19 (42) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0)

TORS: NR TORS: - pT1: 15 (33) - pT2: 18 (40) - pT3: 3 (7) - pT4a: 9 (20) - pT4b: 0 (0)


TORS: - I:2 (4) - II: 4 (9) - III: 7 (16) - IVA: 29 (64) - IVB: 3 (7)


TORS: 27 TORS: NR TORS: 25 (93) TORS: NR TORS: NR TORS: 0 (0) TORS: - BOT: 0 (0) - Tonsil: 27 (100) - Soft palate: 0 (0) - Pharyngeal wall: 0 (0)

TORS: 11 (41) TORS: - cT1: 5 (19) - cT2: 16 (59) - cT3: 6 (22) - cT4: 0 (0)

TORS: - cN0: 4 (15) - cN1: 13 (48) - cN2: 10 (37) - cN3: 0 (0)

TORS: - I: 0 (0) - II: 3 (11) - III: 14 (52) - IVA: 10 (37)

† Values are reported as n (%) ††Values are reported as mean (range) ‡ Study does not inform whether T and N stages were based on clinical or pathological findings [ ] Percentage based on incomplete sample size described in (n=) BOT= Base of Tongue; CRT= Chemoradiotherapy; HNC= Head and Neck Cancer; HPV= Human Papillomavirus; HPV+= Human Papillomavirus Positive test; HPV-= Human Papillomavirus Negative Test; NA= Not Applicable; NR= Not Reported; RT= Radiotherapy; SD= Standard Deviation; TORS= Transoral Robotic Surgery; TOS= Transoral Surgery; TLM= Transoral Laser Microsurgery



Table 4. Characteristics of procedure.

Study Sample

size Robot model Description of neck

dissection (ND) procedure Neck dissection

n (%) Description of adjuvant

therapy Adjuvant therapy

n (%) Surgeons

n

Surgeons’ experience at

the start of the study Learning curve Note

TORS vs. OPEN


TORS: 18 OPEN: 29

TORS: da Vinci S OPEN: NA

TORS: - Time: same session - Indication: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

NR All OPEN procedures used a mandibulotomy approach


TORS: 65 OPEN: 65

TORS: OPEN: NA

TORS: NR OPEN: NR

TORS: 56 (86) OPEN: 56 (86) P>0.99

TORS: NR OPEN: NR

TORS: - RT: 43 (66) - CRT: 17 (26) OPEN: - RT: 40 (62) - CRT: 19 (29) PRT= 0.44 PCRT= 0.56

TORS: 2 OPEN: NR

TORS: NR OPEN: NR

NR OPEN approaches were: transcervical, transfacial, transmandibular and transoral.


TORS: 27 OPEN: 30

TORS: NR OPEN: NA

TORS and OPEN - Time: same session - Indication: elective selective ND (levels I-III) was performed if pN0; otherwise a modified radical ND was performed

TORS: 26 (96) OPEN: 30 (100) P=1.00

TORS and OPEN: - Indication for RT: pT3-4 tumor; close margin (<5mm) - RT dose: NR - Indication for CRT: positive margin; extracapsular spread; multiple positive nodes; and presence of perineural invasion or vascular embolism - Chemotherapy: NR

TORS (n=26): 22 (81)[85] OPEN: 25 (83) - mandibulotomy: 11 (79) - TOS: 14 (88) P=0.81

TORS: 1 OPEN: 1

TORS: NR OPEN: NR

NR OPEN: 14 were conducted with a mandibulotomy approach and 16 had a transoral approach (TOS)


TORS: 64 OPEN: 64

TORS: NR OPEN: NA

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

NR


TORS: 22 OPEN: 14

TORS: NR OPEN: NA

TORS: - Time: same session or in a staged procedure. Some recurrent cases had prior ND - Indication: selective or modified ND

TORS: 16 (73) - Primary cases: 12 (80) - Recurrent cases: 4 (57) OPEN: 13 (93)

TORS and OPEN: - Indication for RT: pT2 BOT lesion; >1 positive node; perineural or lymphovascular invasion - RT dose: NR - Indication for CRT: positive

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

NR




Study Sample





n (%) Surgeons

n



OPEN: - Time: same session - Indication: selective or modified ND

- Recurrent cases: 13 (93) P=NR

margin; extracapsular spread - Chemotherapy: NR

TORS vs. TLM


TORS: 369 TLM: 145

TORS: NR TLM: NA

TORS: NR TLM: NR

TORS: 336 (91) TLM: 115 (79) P<0.001

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: >1 TLM: >1

TORS: NR TLM: NR

NR


TORS: 17 TLM: 16

TORS: da Vinci Si TLM: NA

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

NR



TORS: 160

TORS: da Vinci Si or Xi

TORS: NR TORS: NR TORS: NR TORS: NR TORS: 3 TORS: Initial Inflection point for operative time - Surgeon 1 (n=68): 39 cases - Surgeon 2 (n=37): 30 cases - Surgeon 3 (n=55): 27 cases Inflection point for margin status - Surgeon 1 (n=68): 27 cases - Surgeon 2 (n=37): none




Study Sample





n (%) Surgeons

n



identified - Surgeon 3 (n=55): 25 cases Inflection point for length of hospital stay - No evidence of learning curve Inflection point for nasogastric tube rate - No evidence of learning curve Inflection for readmission rate - - No evidence of learning curve


TORS: 51 TORS: NR TORS: same session (78%) or staged procedure (6%)

TORS: 43 (84) TORS: NR TORS: NR TORS: NR TORS: NR NR


TORS: 30 TORS: da Vinci Si

TORS: - Time: same session - Indication: bilateral ND performed in all BOT or pharyngeal wall cancers. Tonsillar cancers without involvement of midline organs received ipsilateral

TORS: 30 (100) - Bilateral: 9 (30) - Unilateral: 21 (70)

TORS: - Indication for RT: pT2-4; pN2-3 - RT dose: between 60-66Gy at the primary site and 50Gy at the elective neck - Indication for CRT: margin status <2mm; extracapsular

TORS: 6 (20) - RT: 4 (13) - CRT: 2 (7) - Indicated, but declined: 7 (23) - RT: 6 (20) - CRT: 1 (3)

TORS: NR TORS: NR NR




Study Sample





n (%) Surgeons

n



ND. spread - Chemotherapy: cisplatin


TORS: 25 TORS:

TORS: - Time: same session - Indication: NR

TORS: NR

TORS: - Indication for RT: pT3-4; pN2-3; perineural or lymphovascular invasion - RT dose: NR - Indication for CRT: positive margins; extracapsular spread - Chemotherapy: NR

TORS: 0 (0) - Indicated, but declined: 25 (100) - RT: 18 (72) - CRT: 7 (28)

TORS:

TORS:

NR


TORS: 114

TORS: NR TORS: NR TORS: NR TORS: NR TORS: - RT: 69 (61) - CRT: 52 (46)



TORS: 34 TORS: NR TORS: NR TORS: NR TORS: - Indication for RT/ CRT: multiple lymph nodes; positive or close margins; extracapsular spread; perineural invasion - RT dose: NR - Chemotherapy: NR

TORS: 0 (0) - Indicated, but declined: 11 (32)



TORS: 35 TORS: da Vinci Si

TORS: - Time: same session or in a staged procedure - Indication: NR

TORS: NR TORS: - Indication for RT: NR - RT dose: between 60-66Gy - Indication for CRT: NR - Chemotherapy: NR

TORS: 19 (54) - RT: 14 (40) - CRT: 5 (14) - Indicated, but declined: 3 (9)

TORS: one team consisted of a fellowship-trained consultant head and neck surgeon and two surgical assistants

TORS: NR NR


TORS: 13 TORS: NR

TORS: - Time: same session - Indication: NR

TORS: 11 (85) TORS: - Indication for RT/ CRT: >1 positive node; close margins

TORS: 0 (0) TORS: 1 TORS: >50 TORS

NR




Study Sample





n (%) Surgeons

n



(<5mm); extracapsular spread - RT dose: NR - Chemotherapy: NR


TORS: 170

TORS: NR

TORS: NR

TORS: NR TORS: - Indication for RT: NR - RT dose: median 64.3Gy (range: 51.0-73.5Gy) - Indications for CRT: positive margins; extracapsular spread - Chemotherapy: mostly with cisplatin; 3 cases received carboplatin and taxol, and 2 cases received cetuximab

TORS: 170 (100) - RT: 170 (100) - CRT (n=168): 87 (51) [52]



TORS: 29 TORS: NR TORS: - Time: same session - Indication: NR

TORS: NR

TORS: NR

TORS: 17 (59) - Primary cases: 14 (64) - Recurrent cases: 3 (43)



TORS: 81 TORS: NR TORS: - Time: same session - Indication: bilateral ND performed in patients with lesions encroaching the midline

TORS: 79 (98) - Indicated, but declined: 2 (2) ‡ ‡ patients decided to undergo RT

TORS: - Indication for RT/CRT: pT3-4; N2-3; nodal disease in levels IV or V; extracapsular spread; perineural invasion - RT dose: mean 65Gy (range: 60-74Gy) - Chemotherapy: mostly with cisplatin (75%); some received cetuximab (25%)

TORS (n=79): - RT: 69 (85) [87] - CRT: 49 (60) [62]



TORS: 13 TORS: NR TORS: - Time: same session - Indication: always for OPSCC T1-2 disease.

TORS: 7 (54) - Bilateral: 1 (8) - Unilateral: 6 (46) - Indicated, but

TORS: - Indication for RT/ CRT: >1 positive node; close margins (<5mm); extracapsular spread - RT dose: NR

TORS: 5 (38) - RT: 1 (8) - CRT: 4 (31)





Study Sample





n (%) Surgeons

n



declined: 4 (31) ‡ ‡Patients did not undergo ND for the following reasons: ND already dissected; arrhythmia; anaphylactic shock; previous irradiation of the neck

- Chemotherapy: NR


TORS: 39 TORS: NR TORS: - Time: same session - Indication: elective selective ND was performed if pN0; otherwise a modified radical ND was performed

TORS: 35 (90) TORS: - Indication for RT: pT3-4; close margins (<5mm) - RT dose: NR - Indication for CRT: positive margins; extracapsular spread; multiple positive nodes; perineural invasion or vascular embolism - Chemotherapy: NR

TORS: 25 (64) - RT: 21 (54) - CRT: 4 (10)

TORS: NR TORS: Initial experience

NR


TORS: 38 TORS: NR TORS: - Time: staged 1-3 weeks following TORS - Indication: NR

TORS: 32 (84) TORS: - Indication for RT: >1 positive node; close margins - Relative indication for RT: pT4; infiltrative growth patterns; perineural or lymphovascular invasion - RT dose: between 54-66Gy - Indication for CRT: positive margins; extracapsular spread - Relative indications for CRT: extensive multiple nodal

TORS: - RT: 22 (58) - CRT: 7 (18)





Study Sample





n (%) Surgeons

n



metastasis - Chemotherapy: cisplatin


TORS: 66 TORS: da Vinci S

TORS: - Time: same session - Indication: bilateral ND performed in patients with: clinical or radiographic evidence of bilateral or contralateral neck disease; tumors crossing the midline; or tumors nearing the midline with nodal disease in the ipsilateral neck


TORS: - Indication for RT: multiple positive nodes; positive margins; lymphovascular or perineural invasion; grade 4/4 disease; extracapsular spread; desmoplasia; atypical metastatic patterns - RT dose: 60Gy - Indication for CRT: extracapsular spread - Chemotherapy: cisplatin

TORS: 55 (83) - RT: 14 (21) - CRT: 41 (62)



TORS: 30 TORS: NR

TORS: - Time: staged 1-3 weeks following TORS - Indication: selective ND in lymph nodes levels I-III adding level IV as an option in pN0 disease; otherwise ND levels I-V was performed

TORS: 27 (90) TORS: - Indication for RT: endophytic cT3-4; multiple positive nodes; perineural or lymphovascular invasion - RT dose: NR - Indication for CRT: positive margins; extracapsular spread - Chemotherapy: NR

TORS: NR TORS: NR

TORS: NR NR


TORS: 50 TORS: NR TORS: - Time: staged 1-3 weeks following TORS, except 1 case with same session ND - Indication: NR

TORS: 48 (96) - HPV+: 36 (97) - HPV-: 12 (92) - Indicated, but declined: 2 (4)

TORS: - Indication for RT: >1 positive node; close margins - Relative indication for RT: pT4 with growth patterns; perineural invasion; 1 positive node - RT dose: between 54 and 60Gy - Indication for CRT: positive margins; extracapsular spread - Chemotherapy: cisplatin

TORS: 41 (82) - RT: 12 (24) - CRT: 27 (54) - Chemotherapy: 2 (4) HPV+: 33 (89) - RT: 10 (27) - CRT: 21 (57) - Chemotherapy: 2 (5) HPV-: 8 (62)





Study Sample





n (%) Surgeons

n



- RT: 2 (15) - CRT: 6 (46)


TORS: 42 TORS: NR TORS: - Time: staged ND - Indication: NR

TORS: 39 (93) TORS: - Indication for RT: NR - RT dose: mean 61.6Gy - Indication for CRT: positive margins; extracapsular spread - Chemotherapy: NR

TORS: - RT: 32 (76) - CRT: 13 (31)



TORS: 47 TORS: NR TORS: - Time: staged 1-3 weeks following TORS, except 1 case with ND prior to TORS - Indication: selective ND in lymph nodes levels I-III adding level IV as an option in pN0 disease; otherwise ND levels I-V was performed

TORS: 47 (100) TORS: - Indication for RT: pT4; pN2; perineural or lymphovascular invasion - RT dose: 60Gy - Indication for CRT: positive margins; extracapsular spread - Chemotherapy: cisplatin; some cases used carboplatin or cetuximab

TORS: 42 (89) - RT: 13 (28) - CRT: 27 (57) - Chemotherapy: 2 (4) ‡ - Indicated, but declined: 4 (9) - RT: 4 (9) ‡patients had indication for RT, but they did not undergo it as they had previous RT for other cancers



TORS: 45 TORS: da Vinci S

TORS: - Time: same session - Indication: N0-2b and N3 tumors had ipsilateral selective ND (levels I-IV), while N2c or tumors crossing the midline of the tongue base underwent selective bilateral ND


TORS: - Indication for RT/ CRT: >1 positive node; desmoplastic reaction; perineural or angiolymphatic invasion; positive margins; extracapsular spread - RT dose: 60Gy or 65-70Gy when evidence of positive margins - Chemotherapy: NR

TORS: 33 (73) - RT: 8 (28) - CRT: 25 (56) - Indicated, but declined: 1 (2) - RT: 1 (2)

TORS: 3 TORS: Initial Operative time in min as mean (range) TORS: - First 10 cases: - set up time: 69 (54-59) - Total OR time: 313 (106-737)




Study Sample





n (%) Surgeons

n



- Subsequent 35 cases: - set up time: 23 (14-28) - Total OR time: 216 (45-350)


TORS: 27 TORS: NR TORS: - Time: staged 1-3 weeks following TORS - Indication: selective ND in lymph nodes levels I-III adding level IV as an option in pN0 disease; otherwise ND levels I-V was performed

TORS: 26 (96) TORS: - Indications for RT: pT4 with infiltrative growth patterns; >1 positive node; close margins; perineural invasion - RT dose: between 54-66Gy - Indication for CRT: positive margins; extracapsular spread - Chemotherapy: cisplatin

TORS: 25 (93) - RT: 9 (33) - CRT: 15 (56) - Chemotherapy: 1 (4) ‡ ‡1 patient had undergone irradiation before due to a lymphoma and as a result he received only chemotherapy

TORS: 2 TORS: NR NR

[ ] Percentage based on incomplete sample size described in (n=) BOT= Base of Tongue; CRT= Chemoradiotherapy; HPV= Human Papillomavirus; HPV+= Human Papillomavirus Positive test; HPV-= Human Papillomavirus Negative Test; NA= Not Applicable; ND= Neck Dissection; NR= Not Reported; OPSCC= Oropharyngeal Squamous Cell Carcinoma; RT= Radiotherapy; TORS= Transoral Robotic Surgery; TOS= Transoral Surgery; TLM= Transoral Laser Microsurgery



Table 5. Safety.

Study Sample size Adverse events

N (%) Infection rate

n (%) Blood transfusion

n (%) Conversion

n (%)

Equipment failure n (%)

TORS vs. OPEN


TORS: 18 OPEN: 29

TORS: 1 (6) case of hematoma 2 (11) cases of abscess 1 (6) case of chyle leak OPEN: 1 (3) case of hematoma 3 (10) cases of abscess 1 (3) case of chyle leak 3 (10) cases of airway obstruction 1 (3) case of pulmonary embolism 1 (3) case of stroke P=NR

TORS: NR OPEN: NR

TORS: 3 (17) OPEN: 5 (17) P=NR

TORS: 0 (0) OPEN: NA

TORS: NR OPEN: NA


TORS: 65 OPEN: 65

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NA


TORS: 27 OPEN: 30

TORS: No events OPEN: 1 (3) case of flap failure 1 (3) case of malunion 1 (3) case of osteoradionecrosis P=NR

TORS: 0 (0) OPEN: 0 (0)

TORS: NR OPEN: NR

TORS: NR OPEN: NA

TORS: NR OPEN: NA


TORS: 64 OPEN: 64

TORS: 13 (20) cases of airway edema 7 (11) cases of postoperative bleeding OPEN: 4 (6) cases of fistula 12 (19) cases of airway edema 2 (3) cases of malunion 5 (8) cases of bone exposure 3 (5) cases requiring hardware removal 7 (11) cases of free flap compromise

TORS: 6 (9) OPEN: 14 (22) P=0.03

TORS: NR OPEN: NR

TORS: NR OPEN: NA

TORS: NR OPEN: NA



Table 5. Safety.




n (%) Conversion

n (%)


8 (13) cases of postoperative bleeding Pfistula=0.12 Pedema>0.99 Pbleeding>0.05


TORS: 22 OPEN: 14

TORS: - Primary cases: 1 (5) case of respiratory distress 2 (9) cases of postoperative bleeding 1 (5) case of short-term airway edema - Recurrent cases: No events OPEN: - Recurrent cases: 1 (7) case of neck abscess 2 (14) cases of hematoma P=NR

TORS: 2 (9) 2 (9) cases of pneumonia OPEN: 2 (14) 2 (14) cases of wound infection P=NR

TORS: NR OPEN: NR

TORS: NR OPEN: NA

TORS: NR OPEN: NA

TORS vs. TLM


TORS: 369 TLM: 145

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: 6 (2) TLM: 17 (12) P<0.001

TORS: NR TLM: NA


TORS: 17 TLM: 16

TORS: 3 (18) 1 (6) case of tongue paresthesia 1 (6) case of tongue laceration 1 (6) case of MI TLM: 1 (6) 1 (6) case of acute postoperative airway obstruction P=NR

TORS: 0 (0) TLM: 1 (6) 1 (6) case of aspiration pneumonia P=NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NA


Albergotti et al. (2017) TORS: 160 TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR



Table 5. Safety.




n (%) Conversion

n (%)


(9) USA


TORS: 51 TORS: 4 (8) cases of postoperative hemorrhage 1 (2) case of nephrolithiasis

TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 30 TORS: 1 (3) case of swelling of tongue 1 (3) case of severe postoperative bleeding 2 (7) cases of minor postoperative bleeding

TORS: 3 (10) 3 cases of aspiration pneumonia

TORS: NR TORS: NR TORS: NR


TORS: 25 TORS (n=18): No events

TORS (n=18): 0 (0) TORS: NR TORS (n=18): 0 (0)

TORS: NR


TORS: 114 TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR




TORS: 35 TORS: 2 (6) 2 (6) cases of postoperative bleeding



TORS: 13 TORS: 4 (31) 3 (23) cases of postoperative bleeding 1 (8) case of pulmonary embolism

TORS: NR TORS: 0 (0) TORS: NR TORS: NR


TORS: 170 TORS: 47 (28) cases of STN 8 (5) cases of trismus 71 (42) cases of mucositis grade 1-2 81 (48) cases of mucositis grade 3

TORS: NR TORS: NR TORS: 0 (0) TORS: NR




TORS: 81 TORS: 3 (4) cases of hematoma 2 (2) cases of intraoperative fistula

TORS: 0 (0) TORS: NR TORS: NR TORS: NR


TORS: 13 TORS: 3 (23) cases of postoperative bleeding 1 (8) case of intraoperative anaphylactic shock 1 (8) case of intraoperative arrhythmia

TORS: 0 (0) TORS: 0 (0) TORS: NR TORS: NR


TORS: 39 TORS: No events

TORS: 1 (3) 1 (3) case of postoperative pneumonia




Table 5. Safety.




n (%) Conversion

n (%)





TORS: 66 TORS: 5 (8) 1 (2) case of postoperative bleeding 4 (6) cases of pharyngocutaneous fistula

TORS: 0 (0) TORS: NR TORS: 0 (0) TORS: NR


TORS: 30 TORS: 1 (3) case of temporomandibular joint capsulitis 1 (3) case of postoperative seizure 1 (3) case of postoperative bradycardia 1 (3) case of dyspepsia 2 (7) cases of minor bleeding 1 (3) case of acute renal failure 1 (3) case of syncope and dehydration 1 (3) case of mild nasopharyngeal insufficiency

TORS: 0 (0.0) TORS: 0 (0) TORS: 0 (0) TORS: NR




TORS: 42 TORS: No events

TORS: 0 (0) TORS: NR TORS: NR TORS: NR


TORS: 47 TORS: 2 (4) cases of PEG-related complications 2 (4) cases of alcohol withdrawals 1 (2) case of seizure

TORS: 1 (2) 1 (2) case of pneumonia

TORS: 0 (0) TORS: NR TORS: NR


TORS: 45 TORS: 1 (2) case of congestive heart failure 1 (2) case of pulmonary edema 1 (2) case of hematoma 3 (7) cases of orocutaneous fistula 3 (7) cases of trismus 8 (18) cases of prolonged mucosal ulceration 18 (40) cases of xerostomia 17 (38) cases of shoulder pain

TORS: 0 (0) TORS: NR TORS: 0 (0) TORS: NR


TORS: 27 TORS: 5 (19) 1 (4) case of delirium due to alcohol withdrawal 1 (4) case of bleeding 1 (4) case of exacerbation of sleep apnea 2 (7) cases of moderate trismus

TORS: 0 (0) TORS: 0 (0) TORS: NR TORS: NR



Table 5. Safety.




n (%) Conversion

n (%)


1 (4) case of severe hyper nasality of the voice

BOT= Base of Tongue; MI= Myocardial Infarction; NA= Not Applicable; NR= Not Reported; PEG= Percutaneous Endoscopic Gastrostomy; STN= Soft Tissue Necrosis; TORS= Transoral Robotic Surgery; TLM= Transoral Laser Microsurgery; UTI= Urinary Tract Infection



Table 6. Operative and post-operative outcomes.

Study Sample size

EBL in mL Mean ± SD

Median (Range) Reconstruction

N (%)

Pain n (%)

Median [IQR] Surgical margins

n (% positive)

TORS vs. OPEN


TORS: 18 OPEN: 29

TORS: NR OPEN: NR

TORS: 18 (100) - radial forearm free flap: 18 (100) OPEN: 29 (100.0) - radial forearm free flap: 29 (100) P=NA

TORS: NR OPEN: NR

TORS: 0 (0) OPEN: 2 (7) P=0.52


TORS: 65 OPEN: 65

TORS: NR OPEN: NR

TORS: 0 (0) OPEN: NR P=NR

TORS: NR OPEN: NR

TORS: 10 (15) OPEN: 12 (18) P=0.52


TORS: 27 OPEN: 30

TORS: NR OPEN: NR

TORS: 0 (0) OPEN: NR -radial forearm free flap: NR - flap revision: 1 (3) P=NR

TORS: NR OPEN: NR

TORS: 1 (4) OPEN: 3 (10) - mandibulotomy: 1 (7) - TOS: 2 (13) P=0.68


TORS: 64 OPEN: 64

TORS: 49±NR OPEN: 331±NR P<0.001

TORS: 0 (0) OPEN: 48 (75) - free flap: 48 (75) P<0.001

TORS: NR OPEN: NR

TORS: 6 (9) OPEN: 19 (29) P=0.01


TORS: 22 OPEN: 14

TORS: NR OPEN: NR

TORS: NR OPEN: NR - flap revision: 1 (7) P=NR

TORS: NR OPEN: NR

TORS (<4mm): 0 (0) OPEN (<4mm): 2 (14) P=NR

TORS vs. TLM


TORS: 369 TLM: 145

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: 62 (17) TLM: 41 (28)




Study Sample size



N (%)

Pain n (%)


n (% positive)

P=0.003 ORadj= 1.5 (95%CI: 0.9-2.6)


TORS: 17 TLM: 16

TORS: 170±200 TLM: 200±150 P=0.32

TORS: 0 (0) TLM: 0 (0)

TORS: NR TLM: NR

TORS: (≤1mm): 2 (12) TLM (≤1mm): 2 (13) P=1.00



TORS: 160 TORS: NR TORS: 0 (0) TORS: NR TORS: 22 (14)


TORS: 51 TORS: NR TORS: 32 (63) - local flap: 32 (63)

TORS: NR TORS: NR


TORS: 30 TORS: NR TORS: NR - mucosal-constrictor flap: 1 (3)

TORS: NR TORS (0mm): 0 (0) - Close (<2mm): 1 (3)


TORS: 25 TORS: NR TORS: NR TORS: NR TORS (<1mm): 0 (0)


TORS: 114 TORS: NR TORS: NR TORS: NR TORS (positive and close<2mm): 26 (23)


TORS: 34 TORS: NR TORS: NR TORS: - 1month (n=8): 38 [25-75]‡ - 6 months (n=12): 88 [75-100]‡ - 1 year (n=8): 100 [75-100]‡ - 2 years (n=9): 75 [75-75]‡ P6months<0.01‡‡ P1 year=0.01‡‡ P2 yeasr=0.06‡‡ ‡Pain domain of UW-QOL ‡‡Compared to 1 month

TORS: 1 (3)

Lorincz et al. TORS: 35 TORS: NR TORS: NR TORS: NR TORS (<2mm): 2 (6)




Study Sample size



N (%)

Pain n (%)


n (% positive)

(2015) (13) Germany


TORS: 13 TORS: 90 (15-380)†† TORS: NR TORS: NR TORS: 0 (0)


TORS: 170 TORS: NR TORS: NR TORS: 40 (23)‡ - opioids: 21 (12) ‡ Number of patients with pain due to development of adverse event (STN)

TORS: 3 (2)


TORS: 29 TORS: NR TORS: 9 (31)‡ - radial forearm free flap: 7 (24) - free flap and pectoralis major flap: 1 (3) - anterior lateral thigh free flap: 1 (3) ‡Primary cases: 5 (22.7) Recurrent cases: 4 (57.1)

TORS: NR TORS: NR


TORS: 81 TORS: NR TORS: - local uvular mucosal rotational flap closure: 26 (32) - digastric muscle flap: 1 (1)‡ ‡ Patient developed fistula

TORS: NR TORS: 8 (10)


TORS: 13 TORS: 105 (15-420)†† TORS: NR TORS: NR TORS: (<5mm): 1 (8)


TORS: 39 TORS: 10 (5-80) TORS: 0 (0) TORS: NR TORS: 2 (5)


TORS: 38 TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 66 TORS: NR TORS: NR TORS: NR TORS: 1 (2)

Weinstein et al. TORS: 30 TORS: 88 (10-500)†† TORS: NR TORS: NR TORS: 1 (3)




Study Sample size



N (%)

Pain n (%)


n (% positive)

(2012) (19) USA


TORS: 50 TORS: NR TORS: 1 (2) - free tissue transfer: 1 (2)

TORS: NR TORS (<2mm): 1 (2) - Close (2mm): 2 (4) HPV+ (<2mm): 1 (3) - Close (2mm): 1 (3) HPV- (<2mm): 0 (0) - Close (2mm): 1 (8)




TORS: 47 TORS: 220±247 TORS: 0 (0) TORS: NR TORS: 1 (2)





††Values are reported as mean (range) EBL= Estimated Blood Loss; HPV= Human Papillomavirus; HPV+= Human Papillomavirus Positive test; HPV-= Human Papillomavirus Negative Test; NA= Not Applicable; NR= Not Reported; SD= Standard Deviation; STN= Soft Tissue Necrosis; TORS= Transoral Robotic Surgery; TOS= Transoral Surgery; TLM= Transoral Laser Microsurgery; UW-QOL= University of Washington Quality of Life Questionnaire



Table 7. Swallowing-related outcomes.

Study Sample size NG tube

n (%)

Duration of NG in days/ Time to oral intake

Mean ±SD Median (range)

PEG tube placement n (%)

Eating/swallowing function Mean ±SD

Median (range) Median [IQR]

Initially/ Ever Final measure baseline 1 month 6 months 1 year 2 years

TORS vs. OPEN


TORS: 18 OPEN: 29

TORS: 18 (100)* OPEN: 29 (100)* P=NR

TORS: NR OPEN: NR

TORS: 3 (17) OPEN: 4 (14) P=0.68

At 12 months TORS: 1 (6) OPEN: 4 (14) P= 0.50

NR TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 65 OPEN: 65

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 27 OPEN: 30

TORS: NR OPEN: NR

TORS:7±4 OPEN: -mandibulotomy: 17±5 - TOS: 7±8 P<0.001

TORS: 0 (0) OPEN: 0 (0) P=NA

At last FUP: mean 20 months TORS: 0 (0) OPEN: 0 (0) P=NA


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 64 OPEN: 64

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: 23 (36)‡ OPEN: 48 (75) P<0.001 ‡10 (15.6) TORS cases had PEG tube placement preoperatively

At 12 months TORS: 2 (3) OPEN: 20 (31) P=0.002


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 22 OPEN: 14

TORS: 1 (5) OPEN: NR P=NR

TORS: NR OPEN: NR

TORS: 6 (27) OPEN: 9 (64) P=NR

At 6 months TORS: 1 (5) - Primary cases: 1 (5) - Recurrent


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR





n (%)







cases: 0 (0.0) OPEN: 6 (43) - Recurrent cases: 6 (43) P=0.06

TORS vs. TLM


TORS: 369 TLM: 145

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

NR TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR


TORS: 17 TLM: 16

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: 4 (24) TLM: 6 (38) P=0.47

At last FUP: median 15 (range: 7-39) months TORS: 2 (12) TLM: 0 (0) P=0.49

NR TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR



TORS: 160 TORS (n=159): 29 (18) [18]

TORS: NR TORS: NR TORS: NR NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 51 TORS: 6 (12) TORS: 16 (3-31)††

TORS: 1 (2) At 1 month TORS: 1 (2)

EAT-10 Score from 0 (no problem) to 40 (severe problem)

TORS: 21.5±NR‡ ‡1 day after TORS

TORS: 12.2±NR P<0.001



TORS: 30 TORS: 23 (77) TORS: NR (0-35) TORS: 3 (10) At last FUP: mean 19 (range: 9-25) months TORS: 0 (0)

NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR

Funk et al (2016) (10)

TORS: 25 TORS (n=18): 8 (44)

TORS (n=18): 14 (3-24)††

TORS (n=18): 0 (0)

At last FUP: mean± SD 32 ±18

FOSS FOSS has 4

TORS: NR TORS: NR TORS: NR TORS: NR TORS (n=18) † -FOSS 0: 14 (78)





n (%)







USA months TORS (n=18): 0 (0)

stages from 0 (normal) to 4 (severely decompensated)

- FOSS 1: 4 (22) - FOSS 3-5: 0 (0)


TORS: 114 TORS: NR TORS: NR TORS: NR TORS: NR NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 34 TORS: NR TORS: NR TORS: 2 (6) TORS: NR UW-QOL: chewing domain; swallowing domain Each domain ranges from 0 (worst) to 100 (best)

TORS: NR TORS (n=8): - chewing: 50 [50-100] - swallowing: 70 [30-85]

TORS (n=12): - chewing: 100 [50-100] - swallowing: 100 [70-100] Pchewing=0.40‡ Pswallowing=0.05‡ ‡Compared to 1 month

TORS (n=8): - chewing: 100 [100-100] - swallowing: 100 [70-100] Pchewing<0.05‡ Pswallowing=0.07‡ ‡Compared to 1 month

TORS (n=9): - chewing: 100 [100-100] -swallowing: 100 [70-100] Pchewing=0.11‡ Pswallowing=0.05‡ ‡Compared to 1 month


TORS: 35 TORS: 35 (100)*

TORS: 5 (1-25) TORS: 16 (46) At last FUP: median 13 months TORS: 0 (0)



TORS: 13 TORS: 8 (62) TORS: 5 (3-21) TORS: NR TORS: NR MDADI: Each subscale ranges from 0 (low functioning) to 100 (high functioning)

TORS (n=13): - MDADI (global): 76.9±36.4 - MDADI (emotional): 73.9±41.9 - MDADI (functional): 73.9±41.9 MDADI (physical):

TORS: NR TORS (n=13): - MDADI (global): 78.5±28.8 - MDADI (emotional): 75.9±25.8 - MDADI (functional): 76.9±26.4 - MDADI (physical): 71.7±25.9

TORS (n=13): - MDADI (global): 86.2±26.3 - MDADI (emotional): 81.5±26.4 - MDADI (functional): 83.4±26.3 - MDADI (physical):

TORS: NR





n (%)







73.9±41.9 Pglobal=0.15‡ Pemotional=0.69‡ Pfunctional=0.44‡ Pphysical=0.62‡ ‡Compared to baseline

76.8±26.6 Pglobal>0.05‡ Pemotional>0.05‡ Pfunctional>0.05‡ Pphysical>0.05‡ ‡Compared to baseline




TORS: 29 TORS: 14 (48) TORS: NR TORS: 10 (34) - Primary cases: 6 (27) - Recurrent cases: 4 (57)

At 12 months TORS: 6 (21) - Primary cases: 4 (18) - Recurrent cases: 2 (29)



TORS: 81 TORS: 0 (0) TORS: NR TORS (n=77): 18 (22) [23]‡ ‡1 TORS case had existing PEG tube

At last FUP: mean 23 (range: 3- 51) months TORS (n=66): 6 (7) [9] ‡ ‡1 TORS case had existing PEG tube

HNCI:eating function subscale Each subscale ranges from 0 (worst) to 100 (best)

TORS (n=76): 86.3±17.5

TORS (n=64): 64.4±21.7

TORS (n=47): 57.8±24.8

TORS (n=42): 58.5±27.5 P<0.001‡ ‡Compared to baseline

TORS: NR


TORS: 13 TORS: 10 (77) TORS: 8 (3-18)††

TORS: NR TORS: NR DS DS 0: normal swallowing DS 1: minor dysphagia DS 2: gross dysphagia

TORS (n=13)†: - DS 0: 6 (46) - DS 1: 6 (46) - DS 2: 1 (8)


Park et al. TORS: 39 NR TORS: 6 (1- TORS: NR At last FUP: FOSS TORS: NR TORS: NR TORS: NR TORS: NR TORS (n=38)†:





n (%)







(2013) (16) South Korea

18)†† mean ±SD 22±10 months TORS: 0 (0)

FOSS has 4 stages from 0 (normal) to 4 (severely decompensated) Number of patients with velopharyngeal reflux

- FOSS 0-2: 36 (95) - FOSS 3: 1 (3) - Velopharyngeal reflux†: 1 (3)


TORS: 38 TORS: NR TORS: NR TORS: 15 (39) At 12 months TORS:1 (3)

PSS-HN: diet subscale; eating in public subscale Each subscale ranges from 0 (worst) to 100 (best)

TORS (n=38): -PSS-HN (diet): 96.1±17.0 - PSS-HN (eating in public): 96.1±14.9

TORS: NR TORS (n=36): -PSS-HN (diet): 74.4±34.3 - PSS-HN (eating in public): 72.9±29.5 Pdiet<0.001‡ Ppublic<0.001‡ ‡Compared to baseline score

TORS (n=38): -PSS-HN (diet): 84.2±26.3 - PSS-HN (eating in public): 84.9±27.0 Pdiet=0.18‡ Ppublic=0.20‡ ‡Compared to baseline score

TORS: NR


TORS: 66 TORS: 31 (47) TORS: NR TORS: 18 (27) At last FUP: mean 36 (range: 24-45) months TORS: 3 (5)



TORS: 30 TORS: NR TORS: NR TORS: NR At last FUP: mean 33 (range: 18-61) months TORS: 0 (0)




Sinclair et al. TORS: 42 TORS: 1 (2) TORS: NR TORS: 9 (21) At last FUP: MDADI TORS(n=42): TORS(n=38): TORS: NR TORS(n=37): TORS: NR





n (%)







(2011) (21) USA

mean± SD 14±17 months TORS: 0 (0)

Each subscale ranges from 0 (low functioning) to 100 (high functioning)

- global: 76±23 - emotional: 81±14 - functional: 83±15 - physical: 82±17




TORS: 47 TORS: NR TORS: NR TORS: NR At last FUP: mean 26 (range: 18-44) months TORS: 1 (2)



TORS: 45 TORS: 22 (49) TORS: 13 (2-41)††

TORS: 8 (18) At last FUP: mean 12.3 (range: 1-16) months TORS: 0 (0)



TORS: 27 TORS: NR TORS: NR TORS: 27 (100)* At least 6 months TORS: 1 (4)


*Prophylactic tube insertion in all patients † Values are reported as n (%) ††Values are reported as mean (range) [ ] Percentage based on incomplete sample size described in (n=) BOT= Base of Tongue; DS= Dysphagia score; FOSS= Functional Outcomes of Swallowing Scale; FUP: Follow-up; HNCI= Head and Neck Cancer Inventory; HPV= Human Papillomavirus; HPV+= Human Papillomavirus Positive test; HPV-= Human Papillomavirus Negative Test; IQR= Interquartile Range; MDADI= MD Anderson Dysphagia Inventory; NA= Not Applicable; NG= Nasogastric; NR= Not Reported; PEG= Percutaneous Endoscopic Gastrostomy; PSS-HN= Performance Status Scale for Patients with Head and Neck Cancer; SD= Standard Deviation; TORS= Transoral Robotic Surgery; TOS= Transoral Surgery; TLM= Transoral Laser Microsurgery; UW-QOL= University of Washington Quality of Life Questionnaire; VHI-10= Voice Handicap Index-10



Table 8. Speech function.

Study Sample size

Speech/ Voice function Mean ± SD

Median [IQR]

Measure baseline 1 month 6 months 1 year 2 years

TORS vs. OPEN


TORS: 18 OPEN: 29


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 65 OPEN: 65


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 27 OPEN: 30

VHI-10 Score ranges from 0 (no vocal disability) to 40 (high vocal disability)

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: 7.5±8.0 OPEN: - mandibulotomy: 10.7±8.0 - TOS: 11.1±8.0 P>0.05

TORS: NR OPEN: NR


TORS: 64 OPEN: 64


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 22 OPEN: 14


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS vs. TLM


TORS: 369 TLM: 145

NR TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR


TORS: 17 TLM: 16

NR TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR



TORS: 160 NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR



Rubek et al (2017) (23) TORS: 30 NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR



Denmark






TORS: 34 UW-QOL: speech domain Each domain ranges from 0 (worst) to 100 (best)

TORS: NR TORS (n=8): 100 [85-100] TORS (n=12): 100 [70-100] P=0.25‡ ‡Compared to 1 month

TORS (n=8): 100 [85-100] P>0.99‡ ‡Compared to 1 month

TORS (n=9): 100 [100-100] P=0.51‡ ‡Compared to 1 month




TORS: 13 VHI-10 Score ranges from 0 (no vocal disability) to 40 (high vocal disability)

TORS: - VHI-10-emotional: 3.3±11.6 - VHI-10-functional: 3.3±11.6 - VHI-10-physical: 3.3±11.6

TORS: NR TORS: - VHI-10- emotional: 7.8±14.1 - VHI-10-functional: 7.8±14.1 - VHI-10- physical: 7.2±12.9 Pemotional=0.37‡ Pfunctional=0.17‡ Pphysical=0.21‡ ‡Compared to baseline

TORS: - VHI-10- emotional: 6.1±13.7 - VHI-10-functional: 6.1±13.7 - VHI-10- physical: 5.4±12.5 Pemotional>0.05‡ Pfunctional>0.05‡ Pphysical>0.05‡ ‡Compared to baseline

TORS: NR






TORS: 81 HNCI- speech function subscale Each subscale ranges from 0 (worst) to 100 (best)

TORS (n=76): 89.5±16.6

TORS (n=64): 81.7±20.5 TORS (n=47): 78.4±20.6 TORS (n=42): 80.3±20.5 P=0.002‡ ‡Compared to baseline

TORS: NR


TORS: 13 CS CS 0: normal speech CS 1: minor dysphonia CS 2: gross dysphonia

TORS (n=13)†: - CS 0: 12 (92.3) - CS 1: 0 (0.0) - CS 2: 1 (7.7)







TORS: 38 PSS-HN - speech subscale Each subscale ranges from 0 (worst) to 100 (best)

TORS (n=38): 99.3±4.1

TORS: NR TORS (n=36): 86.1±15.2 P<0.001‡ ‡ Compared to baseline

TORS (n=38): 86.2±20.7 P<0.001‡ ‡Compared to baseline

TORS: NR












TORS: 45 CS CS 0: normal speech CS 1: minor dysphonia CS 2: gross dysphonia

TORS (n=45)†: - CS 0: 45 (100.0) - CS 1-2: 0 (0.0)




† Values are reported as n (%) CS= Communication Score; HNCI= Head and Neck Cancer Inventory; IQR= Interquartile Range; NR= Not Reported; PSS-HN= Performance Status Scale for Patients with Head and Neck Cancer; SD= Standard Deviation; TORS= Transoral Robotic Surgery; TOS= Transoral Surgery; TLM= Transoral Laser Microsurgery; UW-QOL= University of Washington Quality of Life Questionnaire; VHI-10= Voice Handicap Index-10



Table 9. Health-related quality of life (HRQOL) outcomes.

Study Sample

size

HRQOL Mean± SD

Cosmesis/ Aesthetic outcomes Mean± SD

Median [IQR]

Time to return to work/ Recovery

time Mean± SD Measure baseline 1 month 6 months 1 year

TORS vs. OPEN


TORS: 18 OPEN: 29


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 65 OPEN: 65


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 27 OPEN: 30


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 64 OPEN: 64


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 22 OPEN: 14


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS vs. TLM


TORS: 369 TLM: 145

NR TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR


TORS: 17 TLM: 16

NR TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR



TORS: 160 NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR







Kaczmar et al (2016) (11)





Study Sample

size

HRQOL Mean± SD


Median [IQR]



USA


TORS: 34 UW-QOL Each domain ranges from 0 (worst) to 100 (best)

TORS: NR TORS (n=8): - activity: 63 [50-88] - anxiety: 70 [30-70] - appearance: 88 [75-100] - chewing: 50 [50-100] - mood: 75 [75-100] - pain: 38 [25-75] - recreation: 75 [63-100] - saliva: 85 [70-100] - shoulder function: 85[70-100] - speech: 100 [85-100] - swallowing: 70 [30-85] - taste: 100 [50-100] - HRQOL: 40 [40-60] - QOL: 50 [40-80] - HRQOL now vs 1 month before cancer: 50 [50-50]

TORS (n=12): - activity: 75 [50-100] - anxiety: 70 [70-100] - appearance: 100 [75-100] - chewing: 100 [50-100] - mood: 75 [50-100] - pain: 88 [75-100] - recreation: 88 [75-100] - saliva: 100 [70-100] - shoulder function: 85 [30-100] - speech: 100 [70-100] - swallowing: 100 [70-100] - taste: 70 [70-85] - HRQOL: 80 [60-100] - QOL: 80 [60-80] - HRQOL now vs 1 month before cancer: 50 [25-75] Pactivity=0.43‡ Panxiety=0.19‡ Pappearance=0.35‡ Pchewing=0.40‡ Pmood=0.66‡ Ppain<0.01‡ Precreation= 0.45‡ Psaliva= 0.85‡ Pshoulder=0.71‡ Pspeech=0.25‡ Pswallowing=0.05‡ Ptaste=0.43‡ PHRQOL= 0.01‡ PQOL= 0.12‡

TORS (n=8): - activity: 100 [75-100] - anxiety: 85 [50-100] - appearance: 100 [75-100] - chewing: 100 [100-100] - mood: 100 [75-100] - pain: 100 [75-100] - recreation: 100 [88-100] - saliva: 100 [70-100] - shoulder function: 100 [85-100] - speech: 100 [85-100] - swallowing: 100 [70-100] - taste: 100 [70-100] - HRQOL: 70 [50-100] - QOL: 80 [50-100] - HRQOL now vs 1 month before cancer: 50 [50-75] Pactivity=0.10‡ Panxiety=0.37‡ Pappearance=0.67‡ Pchewing<0.05‡ Pmood=0.45‡ Ppain=0.01‡ Precreation=0.20‡ Psaliva=0.55‡ Pshoulder= 0.43‡ Pspeech>0.99‡ Pswallowing=0.07‡ Ptaste=0.86‡

TORS: - 1month (n=8): 100 [75-100]‡ - 6 months (n=12): 100 [75-100]‡ - 1 year (n=8): 100 [75-100]‡ - 2 years (n=9): 100 [75-100]‡ P6months=0.35‡‡ P1 year=0.67‡‡ P2 yeasr>0.99‡‡ ‡ Appearance domain of UW-QOL ‡‡Compared to 1 month

TORS: NR




Study Sample

size

HRQOL Mean± SD


Median [IQR]



PHRQOL(1month)>0.99‡ ‡Compared to 1 month

PHRQOL= 0.12‡ PQOL= 0.18‡ PHRQOL(1month)= 0.62‡ ‡Compared to 1 month










TORS: 81 HNCI: speech attitude; eating attitude; social attitude subscale; overall quality of life Each subscale ranges from 0 (worst) to 100 (best)

TORS (n=76): - speech attitude: 84.0±18.4 - eating attitude: 85.5±19.2 - social attitude: 86.9±13.7 - overall quality of life: 76.3±21.7

TORS (n=64): - speech attitude: 80.3±21.5 - eating attitude: 75.5±20.1 - social attitude: 80.2±18.9 - overall quality of life:71.1±20.5

TORS (n=47): - speech attitude: 79.0±20.9 - eating attitude: 49.8±23.3 - social attitude: 80.2±20.3 - overall quality of life:66.0±25.8

TORS (n=42): - speech attitude: 81.4±21.8 - eating attitude: 57.9±30.1 - social attitude: 84.2±21.4 - overall quality of life:76.8±20.5 Pspeech=0.77 Peating<0.001 Psocial=0.37 Pqol= 0.98

HNCI- aesthetic attitude subscale TORS: - Baseline (n=76): 90.1±20.4 - 1 month (n=64): 81.2±25.5 - 3 months (n=49): 83.9±22.5 - 6 months (n=47): 83.1±22.6 - 1 year (n=42): 84.2±24.2 P=0.07‡ ‡1 year score compared to baseline score

TORS: NR




Study Sample

size

HRQOL Mean± SD


Median [IQR]








TORS: 38 SF8: PCS; MCS Each summary score ranges from 0 (low health) to 100 (best health)

TORS (n=38): - PCS: 50.3±9.3 - MCS: 52.5±29.5

TORS: NR TORS (n=36): - PCS: 47.0±10.1 - MCS: 49.4±28.5 PPCS=0.08‡ PMCS>0.05‡ ‡Compared to baseline

TORS (n=38): - PCS: 50.8±8.9 - MCS: 55.1±26.8 PPCS>0.05‡ PMCS>0.05‡ ‡Compared to baseline

TORS: NR TORS: NR















HNCI= Head and Neck Cancer Inventory; HRQOL= Health-related Quality of Life; MCS= Mental Component Summary; NR= Not Reported; PCS= Physical Component Summary; SD= Standard Deviation; SF-




Study Sample

size

HRQOL Mean± SD


Median [IQR]



8= 8 Item Short Form Health Survey; TORS= Transoral Robotic Surgery; TLM= Transoral Laser Microsurgery



Table 10. Oncological Outcomes.

Study Sample size

Follow up in months

Mean± SD Median (range)

Surgical margins n (% positive)

Local recurrence n (%)

Regional recurrence

n (%) Metastasis

n (%)

Disease-free survival

1 year 2 years 3 years

TORS vs. OPEN


TORS: 18 OPEN: 29

NR TORS: 0 (0) OPEN: 2 (7) P=0.52

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 65 OPEN: 65

NR TORS: 10 (15) OPEN: 12 (18) P=0.52

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: 94% OPEN: 85% P=0.04

TORS: 91% OPEN: 75% P=0.04

TORS: 89% OPEN: 73% P=0.04


TORS: 27 OPEN: 30

TORS and OPEN: 20± NR

TORS: 1 (4) OPEN: 3 (10) - mandibulotomy: 1 (7) - TOS: 2 (13) P=0.68

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: 1 (4) 1 case of lung metastasis OPEN: 1 (3) 1 case of lung metastasis P=NR

TORS: NR OPEN: NR

TORS: 96% OPEN: 92% P=0.73

TORS: NR OPEN: NR


TORS: 64 OPEN: 64

NR TORS: 6 (9) OPEN: 19 (29) P=0.01

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: 74% OPEN: 43% P=0.01

TORS: NR OPEN: NR


TORS: 22 OPEN: 14

6 months postoperative

TORS (<4mm): 0 (0) OPEN (<4mm): 2 (14) P=NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS vs. TLM


TORS: 369 TLM: 145

1 month postoperative

TORS: 62 (17) TLM: 41 (28) P=0.003

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR




Study Sample size

Follow up in months




Regional recurrence

n (%) Metastasis

n (%)



ORadj= 1.5 (95%CI: 0.9-2.6)


TORS: 17 TLM: 16

TORS and TLM: 15 (7-39)

TORS: (≤1mm): 2 (12) TLM (≤1mm): 2 (13) P=1.00

TORS: - locoregional recurrence: 0 (0) TLM: -locoregional recurrence: 1 (6) P=NR

TORS: 0 (0) TLM: 0 (0) P=NA

TORS: 100% TLM: 94% P=NR

TORS: NR TLM: NR

TORS: NR TLM: NR



TORS: 160 NR TORS: 22 (14) TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 51 1 month postoperative

TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 30 TORS: 19 (9-25)†† TORS (0mm): 0 (0) - Close (<2mm): 1 (3)

TORS: 1 (3) TORS: 1 (3) TORS: 0 (0) TORS: 93% TORS: NR TORS: NR


TORS: 25 TORS: 32±18 30 (5-73)

TORS (<1mm): 0 (0) TORS: 2 (8) TORS: 3 (12) TORS: 0 (0)

TORS: 79% (95%CI: 64%-97%)

TORS: 79% (95%CI: 62%-97%)

TORS: NR


TORS: 114 TORS: 17 (NR) TORS (positive and close<2mm): 26 (23)

TORS: - locoregional recurrence: 3 (3)

TORS: 5 (4) TORS: NR TORS: -LRRFS: 97% (95%CI: 91%- 100%) - MFS: 92% (95%CI: 98%-81%)

TORS: NR


TORS: 34 TORS: 14 (0.4-38)†† TORS: 1 (3) TORS: 2 (6) TORS: 1 (3) TORS: 0 (0) TORS: NR TORS: NR TORS: NR


TORS: 35 TORS: 13 (NR) TORS (<2mm): 2 (6) TORS: - locoregional recurrence: 4 (11)

TORS: 1 (3) TORS: 86% TORS: NR TORS: NR


TORS: 13 12 months postoperative

TORS: 0 (0) TORS: 0 (0) TORS: 0 (0) TORS: 0 (0) TORS: 100% TORS: NR TORS: NR




Study Sample size

Follow up in months




Regional recurrence

n (%) Metastasis

n (%)




TORS: 170 TORS: 41 (NR) TORS: 3 (2) TORS: 2 (1) TORS: NR TORS: NR TORS: NR TORS: NR TORS: 99%


TORS: 29 TORS: NR (12- 28)



TORS: 81 TORS: 23 (3- 51)††

TORS: 8 (10) TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 13 TORS: 16 (8-27)††

TORS: (<5mm): 1 (8) TORS: 0 (0) TORS: 0 (0) TORS: 0 (0) TORS: 100% TORS: NR TORS: NR


TORS: 39 TORS: 22±10 TORS: 2 (5) TORS: 2 (5) TORS: 0 (0) TORS: 0 (0) TORS: NR TORS: 92% TORS: NR


TORS: 38 TORS: 15 (10-21)††

TORS: NR TORS: 0 (0) TORS: 0 (0) TORS: 0 (0) TORS: 100% TORS: NR TORS: NR


TORS: 66 TORS: 36 (24-45)††

TORS: 1 (2) TORS: - recurrence: 5 (8)

TORS: NR TORS: NR TORS: 92% (range: 83%-96%)


TORS: 30 TORS: 33 (18-61)††

TORS: 1 (3) TORS: 1 (3) TORS: 3 (10) TORS: 0 (0) TORS: NR TORS: NR TORS: NR


TORS: 50 TORS HPV+: 25 (8-44)†† HPV-: 23 (3-42)††

TORS (<2mm): 1 (2) - Close (2mm): 2 (4) HPV+ (<2mm): 1 (3) - Close (2mm): 1 (3) HPV- (<2mm): 0 (0) - Close (2mm): 1 (8)

TORS: 0 (0) TORS: 1 (2) - HPV+: 0 (0) - HPV-: 1 (8)

TORS: 3 (6) - HPV+: 2 (5) - HPV-: 1 (8)

TORS: NR TORS: 92% - HPV+: 95% - HPV-: 85%

TORS: NR


TORS: 42 TORS: 14±17 17 (4-40)

TORS: NR TORS: 0 (0) TORS: 0 (0) TORS: 0 (0) TORS: 100% TORS: NR TORS: NR

Weinstein et al. TORS: 47 TORS: TORS: 1 (2) TORS: 1 (2) TORS: 2 (4) TORS: 4 (9) TORS: 96% TORS: 79% TORS: NR




Study Sample size

Follow up in months




Regional recurrence

n (%) Metastasis

n (%)



(2010) (27) USA

26 (18-44)††


TORS: 45 TORS: 12 (1-16)†† TORS: 0 (0) TORS: 1 (2) TORS: 3 (7) TORS: NR TORS: 91% TORS: NR TORS: NR


TORS: 27 At least 6 months TORS: 2 (7) TORS: 0 (0) TORS: 0 (0) TORS: 1 (4) TORS: NR TORS: NR TORS: NR

††Values are reported as mean (range) CI= Confidence Interval; HPV= Human Papillomavirus; HPV+= Human Papillomavirus Positive test; HPV-= Human Papillomavirus Negative Test; LRRFS= Locoregional Recurrence-free Survival; MFS= Metastasis-free Survival; NA= Not Applicable; NR= Not Reported; SD= Standard Deviation; TORS= Transoral Robotic Surgery; TOS= Transoral Surgery; TLM= Transoral Laser Microsurgery



Table 11. Survival Outcomes.

Study Sample size

Follow up in months


Mortality/ cause of death N (%)

Overall survival rate Disease specific survival

1 year 2 years 3 years 1 year 2 years 3 years

TORS vs. OPEN


TORS: 18 OPEN: 29


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 65 OPEN: 65


TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 27 OPEN: 30

TORS and OPEN: 20± NR

TORS: 0 (0) OPEN: 1 (3) 1 death of unknown cause

TORS: NR OPEN: NR

TORS: 100% OPEN: 97% P=0.35

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 64 OPEN: 64


TORS: NR OPEN: NR

TORS: 74% OPEN: 43% P=0.02

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 22 OPEN: 14

6 months postoperative

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS vs. TLM


TORS: 369 TLM: 145

1 month postoperative

TORS: 4 (1) TLM: 0 (0) P=0.21

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR


TORS: 17 TLM: 16

TORS and TLM: 15 (7-39)

TORS: 0 (0) TLM: 1 (6) 1 case from a second primary lung cancer

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR

TORS: NR TLM: NR




Study Sample size

Follow up in months





P=NR



TORS: 160 NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 51 1 month postoperative



TORS: 30 TORS: 19 (9-25)†† TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 25 TORS: 32±18 30 (5-73)



TORS: 114 TORS: 17 (NR) TORS: 3 (3) 3 deaths related to cancer

TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 34 TORS: 14 (0.4-38)††

TORS: 2 (6) 1 death related to cancer 1 death due to MI



TORS: 35 TORS: 13 (NR) TORS: 1 (3) 1 case of recurrent disease with distant metastasis



TORS: 13 12 months postoperative


Lukens et al. (2014) (14)

TORS: 170 TORS: 41 (NR) TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR




Study Sample size

Follow up in months





USA


TORS: 29 TORS: NR (12- 28)



TORS: 81 TORS: 23 (3- 51)††

TORS: 8 (10) TORS: NR TORS: NR TORS: NR TORS: NR TORS: 92% TORS: NR


TORS: 13 TORS: 16 (8-27)††

TORS: 1 (8) 1 death unrelated to the BOT tumor



TORS: 39 TORS: 22±10 TORS: 1 (3) 1 death related to tonsillar tumor

TORS: NR TORS: 96% TORS: NR TORS: NR TORS: NR TORS: NR


TORS: 38 TORS: 15 (10-21)††



TORS: 66 TORS: 36 (24-45)††

TORS: 3 (5) 3 deaths related to head and neck cancer

TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR 95% (range: 89%- 98%)


TORS: 30 TORS: 33 (18-61)††



TORS: 50 TORS HPV+: 25 (8-44)†† HPV-: 23 (3-42)††

TORS: 6 (12) 2 deaths related to OPSCC 4 deaths unrelated to OPSCC HPV+: 4 (11) 2 deaths related to OPSCC

TORS: 96% HPV+: 97% HPV-: 91%

TORS: 81% HPV+: 81% HPV-: 80%

TORS: NR TORS: 98% HPV+: 97% HPV-: 100%

TORS: 93% HPV+: 90% HPV-: 100%

TORS: NR




Study Sample size

Follow up in months





2 deaths unrelated to OPSCC HPV-: 2 (15) 2 deaths unrelated to OPSCC


TORS: 42 TORS: 14±17 17 (4-40)



TORS: 47 TORS: 26 (18-44)††

TORS: 6 (13) 3 deaths related to advanced OPSCC 3 deaths unrelated to OPSCC

TORS: 96% TORS: 82% TORS: NR TORS: 98% TORS: 90% TORS: NR


TORS: 45 TORS: 12 (1-16)†† TORS: 1 (2) 1 case of suspected MI



TORS: 27 At least 6 months TORS: 0 (0) TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR TORS: NR

††Values are reported as mean (range) BOT= Base of Tongue; HPV= Human Papillomavirus; HPV+= Human Papillomavirus Positive test; HPV-= Human Papillomavirus Negative Test; MI= Myocardial Infarction; NA= Not Applicable; NR= Not Reported; OPSCC= Oropharyngeal Squamous Cell Carcinoma; SD= Standard Deviation; TORS= Transoral Robotic Surgery; TLM= Transoral Laser Microsurgery



Table 12. Resource related outcomes.

Study Sample size

Equipment set-up time in min Mean± SD

Median (range)

Operative time in min Mean± SD

Median (range)

Length of hospital stay in days Mean ± SD

Median (Range) Readmission rate

n (%)

TORS vs. OPEN


TORS: 18 OPEN: 29

TORS: NR OPEN: NA

From induction of general anesthesia to surgical completion (tumor resection, ND and reconstruction) TORS: 900±NR* OPEN: 930±NR* P=0.77

TORS: 14±NR OPEN: 20±NR P=0.03

TORS: NR OPEN: NR


TORS: 65 OPEN: 65

TORS: NR OPEN: NA

TORS: NR OPEN: NR

TORS: NR OPEN: NR

TORS: NR OPEN: NR


TORS: 27 OPEN: 30

TORS: 9±NR OPEN: NA

Tumor resection TORS: 48±8 OPEN: - mandibulotomy: 76±6 - TOS: 35±9 P<0.001

TORS: 15±4 OPEN: - mandibulotomy: 25±6 - TOS: 14±6 P=0.001

TORS: NR OPEN: NR


TORS: 64 OPEN: 64

TORS: NR OPEN: NA

TORS: 111±NR OPEN: 350±NR P<0.001

TORS: 4±NR OPEN: 8±NR P<0.001

TORS: NR OPEN: NR


TORS: 22 OPEN: 14

TORS: NR OPEN: NA

TORS: NR OPEN: NR

TORS: - Primary cases: 2 (NR) - Recurrent cases: 5 (NR) OPEN: - Recurrent cases: 8 (NR) P<0.001

TORS: NR OPEN: NR

TORS vs. TLM


TORS: 369 TLM: 145

TORS: NR TLM: NA

TORS: NR TLM: NR

TORS: 5±6 TLM: 6±15

TORS (n=365): 14 (4) TLM (n=144): 2 (1)




Study Sample size


Median (range)


Median (range)



n (%)

P=0.48

P=0.33


TORS: 17 TLM: 16

TORS: NR TLM: NA

Time of transoral resection TORS: 115±NR TLM (n=12): 170±NR P=0.06

TORS: 3.4±1.4 TLM: 4.3±2.9 P=0.43

TORS: NR TLM: NR



TORS: 160 TORS: NR Time to resection TORS: 79±37

TORS: 2 (1-24) TORS (n=159): 24 (15) [15]


TORS: 51 TORS: NR TORS: NR TORS: NR TORS: 5 (10)


TORS: 30 TORS: NR TORS: NR TORS: 5.3 (2-13)†† TORS: 1 (3)


TORS: 25 TORS: NR TORS: NR TORS (n=18): 3 (1-4)†† TORS: NR








TORS: 13 TORS: 15±9 Tumor resection TORS: - Operative time: 49±16 - Global time: 66±NR

TORS: 7 (3-60) TORS: NR




TORS: 29 TORS: NR TORS: NR TORS: 4 (1-11)†† TORS: NR


TORS: 81 TORS: NR TORS: NR TORS: 4 (1-9)†† TORS: NR


TORS: 13 TORS: 25±7 Tumor resection TORS: - Operative time: 70±18

TORS: 9 (3-30) TORS: NR




Study Sample size


Median (range)


Median (range)



n (%)

- Global time: 95±NR


TORS: 39 TORS: 9±5 TORS: 77±28 - ND: 120±22

TORS: 15±4 TORS: NR






TORS: 30 TORS: NR It does not include ND TORS: 84 (31-152)††

TORS: 4 (1-7)†† TORS: NR




TORS: 42 TORS: NR TORS: NR TORS: 1 (0-2) TORS: NR




TORS: 45 TORS: - First 10 cases: NR (54-59)†† - Subsequent 35 cases: 22 (14-25)††

TORS: - Operative time: tumor resection - First 10 cases: 72 (45-320)†† - Subsequent 35 cases: 71 (6-309)†† - Global time: time in the operating room - First 10 cases: 313 (106-737)†† - Subsequent 35 cases: 216 (45-350)††

TORS: 4 (1-10)†† TORS: NR


TORS: 27 TORS: 9 (2-22)†† It does not include ND TORS: 103 (26-233)††*

TORS: NR TORS: NR

* Converted from hours ††Values are reported as mean (range) [ ] Percentage based on incomplete sample size described in (n=) BOT= Base of Tongue; NA= Not Applicable; ND= Neck Dissection; NR= Not Reported; SD= Standard Deviation; TORS= Transoral Robotic Surgery; TOS= Transoral Surgery; TLM= Transoral Laser Microsurgery



Appendices

Appendix A. Literature search

Limits: English, Humans

Databases

1. PubMed

2. Embase

3. Web of Science

4. Cochrane Library

5. CINAHL

6. EconLit

7. PsycINFO

7. CRD, DARE, NHS EED

8. Clinical Trials.gov

PubMed (www.pubmed.gov)



#39

Search ((((((((((((("robot assisted surgery") OR "robotic surgery")

OR "Robotic Surgical Procedures"[Mesh]) OR davinci) OR "da

vinci") OR "Surgery, Computer-Assisted"[Mesh]) OR "Video-

Assisted Surgery"[Mesh]) OR "general surgery") OR "operative

surgical procedures") OR "surgical procedures") OR "Surgical

Procedures, Operative"[Mesh]) OR surgery)) AND (((((transoral)

OR trans-oral) OR transoralpharyngeal) OR transorally) OR

transoralgastric) 164

#38

Search ((((((((((("robot assisted surgery") OR "robotic surgery") OR

"Robotic Surgical Procedures"[Mesh]) OR davinci) OR "da vinci")

OR "Surgery, Computer-Assisted"[Mesh]) OR "Video-Assisted

Surgery"[Mesh]) OR "general surgery") OR "operative surgical

procedures") OR "surgical procedures") OR "Surgical Procedures,

Operative"[Mesh]) OR surgery 4113392

#37 Search "robot assisted surgery" 603

#36 Search "robotic surgery" 4415

#35 Search "Robotic Surgical Procedures"[Mesh] 2611

#31 Search davinci 351

#30 Search "da vinci" 4250

#29 Search "Surgery, Computer-Assisted"[Mesh] 15947

#27 Search "Video-Assisted Surgery"[Mesh] 7399

#25 Search "general surgery" 89848

#24 Search "operative surgical procedures" 52183

#23 Search "surgical procedures" 328882

#22 Search "Surgical Procedures, Operative"[Mesh] 2761714

#20 Search surgery 4103906

#19

Search ((((transoral) OR trans-oral) OR transoralpharyngeal) OR

transorally) OR transoralgastric OR tors 3617

#1 Search transoral 3307

#16 Search trans-oral 188

#15 Search transoralpharyngeal 3



#16 Search transoralgastric 2

#17 Search tors 295

Embase

1. transoralpharyngeal.mp. 3

2. trans-oral.mp. 327

3. transoral.mp. 4469

4. transoralgastric.mp. 1

5. tors.mp. 618

6. 1 or 2 or 3 or 4 or 5 4762

7. exp surgery/ or surgery.mp. 4802893

8. Surgical Procedures, Operative.mp. 715

9. surgical procedures.mp. 67980

10. "operative surgical procedures".mp. 88

11. exp general surgery/ 12763

12. exp computer assisted surgery/ 9777

13. "da vinci".mp. 5151

14. davinci.mp. 1029

15. exp robotic surgical procedure/ 1654

16. "robotic surgery".mp. 6672



17. exp robot assisted surgery/ 4390

18. 7 or 8 or 9 or 10 or 11 or 12 or 4810871

13 or 14 or 15 or 16 or 18

19. 6 and 19 106

Web of Science

#19 #17 AND #5 1920

#18 #16 OR #15 OR #14 OR #13 OR #12 OR #11

OR #10 OR #9 OR #8 OR #7 OR #6 756,185

#17 TOPIC: ("robot assisted surgery") 640

#16 TOPIC: ("robotic surgery") 2486

#15 TOPIC: ("robotic surgical procedure*") 157

#14 TOPIC: (davinci) 777

#13 TOPIC: ("da vinci") 3448

#12 TOPIC: ("computer assisted surgery") 1725

#11 TOPIC: ("general surgery") 7396

#10 TOPIC: ("surgical procedures") 39733



#9 TOPIC: ("operative surgical procedures") 72

#8 TOPIC: (Surgical Procedures, Operative) 25435

#7 TOPIC: (surgery) 734412

#6 # 5 OR #4 OR #3 OR #2 OR #1 3463

#5 TOPIC: tors 212

#4 TOPIC: (transoralgastric) 1

#3 TOPIC: (transoral) 3330

#2 TOPIC: (trans-oral) 166

#1 TOPIC: (transoralpharyngeal) 5

Cochrane Library

#1 trans-oral:ti,ab,kw (Word variations have been searched) 12

#2 transoral 193

#3 transoralgastric 0

#4 tors 23

#5 #1 or #2 or #3 or #4 205

#6 surgery 164283

#7 Surgical Procedures, Operative 6085



#8 "operative surgical procedures" 8

#9 "surgical procedures" 17440

#10 "general surgery" 2827

#11 "computer assisted surgery" 223

#12 "da vinci" 173

#13 davinci 31

#14 "robotic surgical procedure*" 105

#15 "robotic surgery" 270

#16 "robot assisted surgery" 255

#17 #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 166916

or #14 or #15 or #16

#18 #17 and #5 22

CINAHL

S18 S5 AND S17 4

S17 (S6 OR S7 OR S9 OR S10 OR S11

OR S12 OR S13 OR S14 OR S15 OR S16 OR S17) 99

S16 "robot assisted surgery" 94



S15 "robotic surgery" 730

S14 "robotic surgical procedure*" 636

S13 "da vinci" 334

S12 davinci 34

S11 "computer assisted surgery" 211

S10 "general surgery" 1432

S9 "surgical procedures" 7688

S8 "operative surgical procedures" 19477

S7 Surgical Procedures, Operative 5387

S6 surgery 372452

S5 S1 OR S2 OR S3 OR S4 1295

S4 transoralgastric 0

S3 tors 465

S2 transoral 888

S1 trans-oral 36

EconLit



S18 S5 AND S17 0

S17 (S6 OR S7 OR S9 OR S10 OR S11

OR S12 OR S13 OR S14 OR S15 OR S16 OR S17) 582

S16 "robot assisted surgery" 0

S15 "robotic surgery" 3

S14 "robotic surgical procedure*" 0

S13 "da vinci" 27

S12 davinci 0

S11 "computer assisted surgery" 0

S10 "general surgery" 10

S9 "surgical procedures" 49

S8 "operative surgical procedures" 77

S7 Surgical Procedures, Operative 4

S6 surgery 519

S5 S1 OR S2 OR S3 OR S4 731

S4 transoralgastric 0

S3 tors 304

S2 transoral 415



S1 trans-oral 12

PsychINFO

1. transoralpharyngeal.mp. 0

2. trans-oral.mp. 48

3. transoral.mp. 97

4. transoralgastric.mp. 0

5. tors.mp. 42

6. 1 or 2 or 3 or 4 or 5 187

7. exp surgery/ or surgery.mp. 9715

8. Surgical Procedures, Operative.mp. 512

9. surgical procedures.mp. 21064

10. "operative surgical procedures".mp. 0

11. exp general surgery/ 4002

12. exp computer assisted surgery/ 812

13. "da vinci".mp. 105

14. davinci.mp. 0

15. exp robotic surgical procedure/ 54



16. "robotic surgery".mp. 71

17. exp robot assisted surgery/ 112

18. 7 or 8 or 9 or 10 or 11 or 12 or 36447

13 or 14 or 15 or 16 or 18

19. 6 and 18 0

CRD, DARE, NHS EED

1 MeSH DESCRIPTOR Robotic Surgical Procedures EXPLODE ALL TREES 1

2 ("robot assisted surgery") 2

3 ("robotic surgery") 58

4 (davinci) 3

5 ("da vinci") 39

6 ("computer assisted surgery") 28

7 ("video assisted surgery") 17

8 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 148

9 (tors) 1

10 (transoral) 19

11 #9 OR #10 19

12 #8 AND #11 23

Clinical Trials.gov = 24

24 studies found for: (tors OR transoral AND "robot assisted surgery” OR "robotic surgery” OR “robotic assisted surgery" OR “davinci” OR “da

Vinic”)



Google (www.google.ca)

(tors OR transoral AND "robot assisted surgery” OR "robotic surgery” OR “robotic assisted surgery" OR “davinci” OR “da vinci”)

http://www.google.ca/

Appendix B. Included studies

Table B1. Key Characteristics of Included Studies.

Study Study Period (country) Design Number of Centers Studies from the Same Center(s) Number of Participants Matching Variables Follow-up (months) Endpoints

TORS vs. OPEN

Biron et al. (2017) (4)

TORS: May 2015- Jul 2016 OPEN: Jan 2006- July 2016 (Canada)

Retrospective cohort Single (UofA)

TORS: 18 OPEN: 29

Unmatched NR Adverse events

Conversion/ equipment failure

Equipment set up/ operative time

Hospital stay

Surgical margins

Swallowing-related outcomes

Tracheostomy

Ford et al. (2014) (5) TORS: Apr 2007- Sep 2011 OPEN: Oct 2004- Aug 2011 (USA)

Retrospective cohort Single (University of Alabama)

White et al. 2013 Sinclair et al. 2011 Dean et al. 2010

TORS: 65 OPEN: 65

TNM stage NR Reconstruction

Recurrence

Surgical margins

Lee et al. (2014) (6) TORS and OPEN: May 2008- Oct 2011 (South Korea)

Prospective cohort Single (Yonsei University)

Park et al. 2013 TORS: 27 OPEN: 14 (mandibulotomy) and 16 (TOS)

Unmatched Mean Overall: 20

Adverse events


Hospital stay

Reconstruction

Recurrence

Speech function

Surgical margins

Survival/ mortality


Tracheostomy

White et al. (2013) (7)

TORS: 2007-Oct 2011 OPEN: Mar 2003- Oct 2011 (USA)

Retrospective cohort Multiple: USA x4 (University of Alabama; Mayo clinic Rochester; Anderson cancer center; Henry Ford Hospital)

Funk et al. 2016 Ford et al 2014 Al-Khudari et al. 2013 Moore et al 2012 Sinclair et al. 2011 Dean et al. 2010 Moore et al 2009

TORS: 64 OPEN: 64

Age Gender N stage T stage

NR Adverse events



Hospital stay

Infection rate

Reconstruction

Recurrence

Surgical margins

Survival/ mortality


Tracheostomy

Dean et al. (2010) (8) TORS: Mar 2007- Jul 2008 OPEN: Jan 2001- Jul 2008 (USA)

Retrospective cohort Single (Univ of Alabama)

Ford et al 2014 White et al. 2013 Sinclair et al. 2011

TORS: 22 OPEN: 14

Unmatched 6 months postoperative Adverse events

Hospital stay

Infection rate

Reconstruction

Surgical margins


Tracheostomy

TORS VS. TLM





Zevallos et al. (2016) (31)

TORS and TLM: 2010- 2011 (USA)

Retrospective cohort, consecutive

Multiple NCDB database

Studies from the USA TORS: 369 TLM: 145

Multivariable analysis: Age Comorbidity index Facility case volume HPV status N stage T stage Treatment facility Tumor site Tumor size

1 month postoperative Conversion/ equipment failure

Hospital stay

Readmission rate

Surgical margins

Survival/ mortality

Sumer et al. (2013) (30)

TORS and TLM: Aug 2008- Dec 2010 (USA)

Retrospective cohort, consecutive

Single (Univ. of Texas Southwestern Medical center)

TORS: 17 TLM: 16

Unmatched Median (range) Overall: 15 (7-39)

Adverse events



Hospital stay

Infection rate

Reconstruction

Recurrence

Surgical margins

Survival/ mortality


Tracheostomy



TORS: Mar 2010 – Mar 2016 (USA)

Case series Single (University of Pittsburgh Medical Centre)

Albergotti et al. (2017b) Choby et al. (2015)

TORS: 160 Unmatched NR Equipment set up/ operative time

Hospital stay

Learning curve

Readmission rate

Surgical margins



TORS: Jun 2014 – Mar 2016 (USA)

Single-arm trial, consecutive

Single (University of Pittsburgh Medical Centre)

Albergotti et al. (2017) Choby et al. (2015)

TORS: 51 Unmatched 1 month postoperative Adverse events

Readmission rate

Reconstruction


Rubek et al (2017) (23)

TORS: Sep 2014- Jan 2016 (Denmark)


Single TORS: 30 NA Mean (range) TORS: 19 (9-25)

Adverse events

Hospital stay

Infection rate

Readmission rate

Reconstruction

Recurrence

Surgical margins


Tracheostomy

Funk et al (2016) (10)

TORS: 2007- 2013 (USA)

Case series Single (Mayo Clinic Rochester)

White et al. 2013 Moore et al 2012 Moore et al 2009

TORS: 25 NA Mean± SD Median (range) TORS: 32±18 30 (5-73)

Adverse events‡

Conversion/ equipment failure‡

Hospital stay‡

Infection rate‡

Recurrence

Surgical margins

Survival/ mortality





Swallowing-related outcomes‡

Tracheostomy‡ ‡Data taken from Olsen et al. 2013 (35)

Kaczmar et al (2016) (11)

TORS: Jan 2010- Aug 2012 (USA)

Case series Multiple: USA x2 (Hospital of the university of Pennsylvania; Pennsylvania Hospital)

Lukens et al 2014 Leonhardt et al. 2012 Weinstein et al. 2012 Cohen et al. 2011 Weinstein et al. 2010 Weinstein et al. 2007

TORS: 114 NA Median TORS: 17

Recurrence

Surgical margins

Survival/ mortality


TORS: May 2010 –Mar 2014 (USA)

Case series Single (University of Pittsburgh Medical Centre)

Albergotti et al. (2017) Albergotti et al. (2017b)

TORS: 34 NA Mean (range) TORS: 14 (0.4-38)

Aesthetic outcomes

HRQOL

Pain

Recurrence

Speech function

Surgical margins

Survival/ mortality


Tracheostomy

Lorincz et al. (2015) (13)

TORS: Sep 2011- Apr 2013 (Germany)

Case series Single TORS: 35 NA Median TORS: 13

Adverse events

Recurrence

Surgical margins

Survival/ mortality


Tracheostomy

Mercante et al. (2015) (24)

TORS: Nov 2010- Oct 2013 (Italy)


Single Mercante et al. 2013 TORS: 13 NA 12 months postoperative

Adverse events

Blood transfusion



Hospital stay

HRQOL

Recurrence

Speech function

Surgical margins

Survival/ mortality


Tracheostomy

Lukens et al. (2014) (14)

TORS: 2006- 2012 (USA)

Case series Single (Univ. of Pennsylvania)

Kaczmar et al 2016 Leonhardt et al. 2012 Weinstein et al. 2012 Cohen et al. 2011 Weinstein et al. 2010 Weinstein et al. 2007

TORS: 170 NA Median TORS: 41

Adverse events

Pain

Recurrence

Surgical margins

Al-Khudari et al. (2013) (15)

TORS: Mar 2010- Jul 2012 (USA)

Case series Single (henry Ford hospital)

White et al. 2013 TORS: 29 NA Range TORS: 12- 28

Hospital stay

Reconstruction


Tracheostomy

Dziegielewski et al. (2013)(32)

TORS: Apr 2008- Sep 2012 (USA)

Single-arm trial Single (Ohio state) TORS: 81 NA Mean (range) TORS: 23 (3- 51)

Adverse events

Aesthetic outcomes





USA Hospital stay

HRQOL

Infection rate

Reconstruction

Speech function

Surgical margins

Survival/ mortality


Tracheostomy

Mercante et al. (2013) (26)

TORS: Oct 2010- Feb 2012 (Italy)


Single Mercante et al. 2015 TORS: 13 NA Mean (range) TORS: 16 (8-27)

Adverse events

Blood transfusion



Hospital stay

Infection rate

Recurrence

Speech function

Surgical margins

Survival/ mortality


Tracheostomy

Park et al. (2013) (16)

TORS: Apr 2008- Sep 2011 (South Korea)

Case series Single (yonsei) Lee et al. 2014 TORS: 39 NA Mean± SD TORS: 22±10

Adverse events



Hospital stay

Infection rate

Reconstruction

Recurrence

Surgical margins

Survival/ mortality


Tracheostomy

Leonhardt et al. (2012) (17)

TORS: Nov 2007- Aug 2009 (USA)

Case series Single (university of Pennsylvania)

Kaczmar et al 2016 Lukens et al 2014 Weinstein et al. 2012 Cohen et al. 2011 Weinstein et al. 2010 Weinstein et al. 2007

TORS: 38 NA Mean (range) TORS: 15 (10-21)

HRQOL

Recurrence

Speech function


Tracheostomy

Moore et al (2012) (18)

TORS: Mar 2007- Feb 2009 (USA)

Case series Single (Mayo clinic Rochester)

Funk et al. 2016 White et al. 2013 Moore et al 2009


Adverse events


Infection rate

Recurrence

Surgical margins

Survival/ mortality


Tracheostomy

Weinstein et al. (2012) (19)

TORS: Aug 2005- Feb 2010 (USA)


Kaczmar et al 2016 Lukens et al 2014 Leonhardt et al. 2012


Adverse events

Blood transfusion






Cohen et al. 2011 Weinstein et al. 2010 Weinstein et al. 2007



Hospital stay

Infection rate

Recurrence

Surgical margins

Survival/ mortality


Tracheostomy

Cohen et al. (2011) (20)

TORS: May 2005- Nov 2007 (USA)


Kaczmar et al 2016 Lukens et al 2014 Leonhardt et al. 2012 Weinstein et al. 2012 Weinstein et al. 2010 Weinstein et al. 2007

TORS: 50 NA Mean (range) TORS HPV positive: 25 (8-44) TORS HPV negative: 23 (2.5-42)

Reconstruction

Recurrence

Surgical margins

Survival/ mortality

Tracheostomy

Sinclair et al. (2011) (21)

TORS: Mar 2007- Apr 2010 (USA)

Case series Single (univ of Alabama)

Ford et al 2014 White et al. 2013 Dean et al. 2010

TORS: 42 NA Mean± SD Median (range) TORS: 14±17 17 (4-40)

Adverse events

Infection rate

Hospital stay

HRQOL

Recurrence

Survival/ mortality


Tracheostomy


TORS: May 2005- Jul 2007 (USA)


Single (university of Pennsylvania)

Kaczmar et al 2016 Lukens et al 2014 Leonhardt et al. 2012 Weinstein et al. 2012 Cohen et al. 2011 Weinstein et al. 2007


Adverse events

Blood transfusion


Infection rate

Reconstruction

Recurrence

Surgical margins

Survival/ mortality


Tracheostomy

Moore et al (2009) (28)

TORS: Mar 2007- Jan 2008 (USA)


Single (mayo clinic) Funk et al. 2016 Moore et al. 2012 White et al. 2013


Adverse events




Hospital stay

Infection rate

Learning curve

Recurrence

Speech function

Surgical margins

Survival/ mortality


Tracheostomy


TORS: May 2005- Apr 2007 (USA)

Single arm trial, consecutive

Single (university of Pennsylvania)

Kaczmar et al 2016 Lukens et al 2014 Leonhardt et al. 2012

TORS: 27 NA At least 6 months Adverse events

Blood transfusion






Weinstein et al. 2012 Weinstein et al. 2010 Cohen et al. 2011


Infection rate

Recurrence

Surgical margins

Survival/ mortality


Tracheostomy

APR-DRGs= All Patient Refined Diagnosis Related Groups; BOT= Base of Tongue; HPV= Human Papillomavirus; HRQOL= Health-related Quality of Life; NA= Not Applicable; NCDB= National Cancer Database; NR= Not Reported; SD= Standard Deviation; TORS= Transoral Robotic Surgery; TOS= Transoral Surgery; TLM= Transoral Laser Microsurgery



Appendix C. Excluded studies

Summary of excluded studies and rationale for exclusion

Excluded studies Reason

Chung TK, Rosenthal EL, Magnuson JS, Carroll WR. Transoral robotic surgery for oropharyngeal and tongue cancer in the United States. Laryngoscope. 2015 Jan;125(1): 140-145

Comparison group not relevant

Geltzeiler M, Doerfler S, Turner M, Albergotti WG, Kubik M, Kim S, Ferris R, Duvvuri U. Transoral robotic surgery for management of cervical unknown primary squamous cell carcinoma: Updates on efficacy, surgical technique and margin status. Oral Oncology 2017 Mar; 66: 9-13.

Population not relevant

Hammoudi K, Pinlong E, Kim S, Bakhos D, Morinière S. Transoral robotic surgery versus conventional surgery in treatment for squamous cell carcinoma of the upper aerodigestive tract. Head Neck 2015 Sep; 37(9): 1304-1309


Kucur C, Durmus K, Teknos TN, Ozer E. How often parapharyngeal space is encountered in TORS oropharynx cancer resection. Eur Arch Otorhinolaryngol. 2015 Sep; 272(9): 2521-2526

Irrelevant outcomes

Laccourreye O, Malinvaud D, Garcia D, Ménard M, Hans S, Cauchois R, Bonfils P. Postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx. Ann Otol Rhinol Laryngol. 2015 May; 124(5): 361-367.

Intervention group not relevant

Ling DC, Chapman BV, Kim J, Choby GW, Kabolizadeh P, Clump DA, Ferris RL, Kim S, Beriwal S, Heron DE, Duvvuri U. Oncologic outcomes and patient-reported quality of life in patients with oropharyngeal squamous cell carcinoma treated with definitive transoral robotic surgery versus definitive chemoradiation. Oral Oncology 2016 Oct;61: 41-46


More YI, Tsue TT, Girod DA, Harbison J, Sykes KJ, Williams C, Shnayder Y. Functional swallowing outcomes following transoral robotic surgery vs primary chemoradiotherapy in patients with advanced-stage oropharynx and supraglottis cancers. JAMA Otolaryngol Head Neck Surg. 2013 Jan; 139(1): 43-48


Olsen SM, Moore EJ, Laborde RR, Garcia JJ, Janus JR, Price DL, Olsen KD. Transoral surgery alone for human-papillomavirus-associated oropharyngeal squamous cell carcinoma. Ear Nose Throat J. 2013 Feb;92(2):76-83

Patients included in another study

Park YM, Holsinger FC, Kim WS, Park SC, Lee EJ, Choi EC, Koh YW. Robot-assisted selective neck dissection of levels II to V via a modified facelift or retroauricular approach. Head and Neck Surgery. 2013 Feb; 148(5): 778-785


Pollei TR, Hinni ML, Moore EJ, Hayden RE, Olsen KD, Casler JD, Walter LC. Analysis of postoperative bleeding and risk factors in transoral surgery of the oropharynx. JAMA Otolaryngol Head Neck Surg. 2013 Nov;139(11):1212-1218

Population unclear

Quon H, Cohen MA, Montone KT, Ziober AF, Wang LP, Weinstein GS, O'Malley BW Jr. Transoral robotic surgery and adjuvant therapy for oropharyngeal carcinomas and the influence of p16 INK4a on treatment outcomes. Laryngoscope. 2013 Mar;123(3):635-640


Richmon JD, Quon H, Gourin CG. The effect of transoral robotic surgery on short-term outcomes and cost of care after oropharyngeal cancer surgery. Laryngoscope. 2014 Jan; 124(1):165-171


Richmon JD, Agrawal N, Pattani KM. Implementation of a TORS program in an academic medical center. Laryngoscope. 2011 Nov; 121(11): 2344-2348

Population unclear

Sharma A, Patel S, Baik FM, Mathison G, Pierce BH, Khariwala SS, Yueh B, Schwartz SM, Méndez E. Survival and Gastrostomy Prevalence in Patients With Oropharyngeal Cancer Treated With Transoral Robotic Surgery vs Chemoradiotherapy. JAMA Otolaryngol Head Neck Surg. 2016 Jul 1;142(7):691-697


Smith RV, Schiff BA, Garg M, Haigentz M. The impact of transoral robotic surgery on the overall treatment of oropharyngeal cancer patients. Laryngoscope. 2015 Nov; 125 Suppl 10:S1-S15


Su HK, Ozbek U, Likhterov I, Brant J, Genden EM, Urken ML, Chai RL. Safety of transoral surgery for oropharyngeal malignancies: An analysis of the ACS NSQIP. Laryngoscope. 2016 Nov;126(11):2484-2491

Intervention group not relevant

van Loon JWL, Smeele LE, Hilgers FJM, van den Brekel MWM. Outcome of transoral robotic surgery for stage I–II oropharyngeal cancer. Eur Arch Otorhinolaryngol. 2015 Jan; 272(1): 175-183




Villanueva NL, de Almeida JR, Sikora AG, Miles BA, Genden EM. Transoral robotic surgery for the management of oropharyngeal minor salivary gland tumors. Head Neck. 2014 Jan; 36(1): 28-33


Weinstein GS, Quon H, O'Malley BW Jr, Kim GG, Cohen MA. Selective neck dissection and deintensified postoperative radiation and chemotherapy for oropharyngeal cancer: a subset analysis of the University of Pennsylvania transoral robotic surgery trial. Laryngoscope. 2010 Sep; 120(9): 1749-1755


https://www.ncbi.nlm.nih.gov/pubmed/20717944

Appendix D. Quality of included studies

Figure D1. Chart of Downs and Black scores by domain for nonrandomized comparative studies

0

5

10

15

20

Internal validity: selectionbias

Internal validity: bias

External validity

Reporting



Table D1. Grade assessment of TORS vs open

Outcomes № of participants

(studies)

Quality of the evidence (GRADE)

Relative effect

(95% CI)

Anticipated absolute effects

Risk with open surgery

Risk difference with TORS

Overall survival at 1 year 50 (1 observational study)

⨁◯◯◯ VERY LOW

a

not estimable

- 0 (0 to 0 )

Disease-free survival rate at 1 year 130 (1 observational study)


b

- not pooled not pooled

Chronic gastrostomy rate Follow up: range 12 months to 20 months

246 (3 observational studies)

⨁◯◯◯

VERY LOW c,d

not pooled not pooled not pooled

Chronic tracheostomy rate Follow up: range 6 months to 20 months



c,d

not pooled not pooled not pooled

Swallowing function (4 observational studies)

⨁◯◯◯

VERY LOW a

No decline in swallowing function was reported in studies with early stage of cancer. However, significant decline was seen from before and 1 year of follow up in a study with advanced stages of cancer

Blood transfusion 34 (1 observational study)


c,e

not estimable

294 per 1,000

294 fewer per 1,000 (294 fewer to 294 fewer)

Adverse events (3 observational studies)


c,d

Overall, few adverse events were described in both surgical groups.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval

a. Case series study with no results for the comparison group b. Failure to control for confounding variable; patients from different groups recruited at different periods of time c. Patients were recruited at different periods of time d. Low event rate e. Inclusion of only patients with advanced cancer stage



Table D2. Grade assessment of TORS vs TLM

Outcomes

№ of participants

(studies) Follow-up

Quality of the

evidence (GRADE)

Relative effect

(95% CI)

Anticipated absolute effects

Risk with TLM

Risk difference with TORS

Overall survival rate at 1 year 50 (1 observational study)


a

- - 0 (0 to 0 )

Disease-free survival rate at 1 year 33 (1 observational study)

⨁◯◯◯ VERY LOW b,c

not estimable

63 per 1,000

63 fewer per 1,000 (63 fewer to 63 fewer)

Chronic gastrostomy tube 33 (1 observational study)


not estimable

0 per 1,000 0 fewer per 1,000 (0 fewer to 0 fewer)

Swallowing function follow up: range 1 month to 61 months

(4 observational studies)


a

No decline in swallowing function was reported in studies with early stage of cancer. However, significant decline was seen from before and 1 year of follow up in a study with advanced stages of cancer.

Tracheostomy follow up: range 3 months to 51 months


⨁◯◯◯ VERY LOW a,d

not pooled

not pooled not pooled

Blood transfusion 43 (2 observational studies)

⨁◯◯◯ VERY LOW a,c

- - -

Adverse events (1 observational study)


Only 3 (18%) patients in the TORS group and 1 (6%) patient in TLM reported adverse events

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval

a. Case series study with no results for the comparison group b. Most patients included are at advanced stage c. Small sample size and low event rate d. Low event rate



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