How to deal with synchronous primary and liver metastases

How to deal with synchronousprimary and liver metastases

Luis Sabater Ortí MD, PhDAssociate Professor University of ValenciaEuropean Board Surgical Qualification HBP (EBSQ-HPB)Department of Surgery. Liver-Biliary and Pancreatic UnitHospital Clínico. University of Valencia

DISCLOSURE

Nothing to disclose

Painting: Sandra Villa LagoPhotograph: David Gimeno VesesSchool of Medicine. Universitat de Valencia

Definitions

SYNCHRONIC Metastasis

Diagnosed at the same time as the CRC

Pre-operative stagingIntraoperative finding (urgent surgery CRC)

3-6 months after resection

20-30 % of patients with CRC

SIMULTANEOUS SURGERY (Vogt P, 1991)

SEQUENTIAL BOWEL-FIRST (80s and two-staged in 2000, Adam R)

SEQUENTIAL LIVER FIRST (Mentha G, 2006)

Advantages Disadvantages

Avoid two operations Long surgical time

Beneficial psycological effects Specialised surgeons required

Resection of all disease, lower riskof dissemination

The biological behaviour of the tumor is not observed

Chemo starts early and in betteroncological conditions

Safety of bowel anastomosis

Less morbidity Higher risk of occult livermetastases

Shorter length hospital stay Bacterial contamination

Lower costs Infection / sepsis

Simultaneous: All liver metastases and the primary tumorare resected in the same operation

Definitions, advantages and disadvantages


Less surgical time for each surgicaloperation

Two surgical operations

No accumulation of risks in each surgery Psychological effects

Better management of complex surgeries Longer length of hospital stay

Allows evaluation of tumor behaviour If complications, delays liver surgery or Chemo

With Chemo occult liver M1 or microM1 are treated

Increase in morbidity

With Chemo reduces M1 size: lessparenchyma resection and higher R0

If interval Chemo, toxicity may appearIf interval Chemo, M1 can disappear

Evaluation response to Chemo and tolerance

Disease progression

Less recurrence rate (?) Unresectability

Disease free survival longer (?) Higher costs

Sequential bowel-first: First resection of the CRC and then the liver metastases.With or without Chemo during the interval.


Sequential bowel-first:Resection of the primary CRC and clearance of theless invaded liver.Then, complete resection of the liver metastases(after hypertrophy of the FLR)

PORTAL

Embolization



Chemo treatment of liver metastases and the primary CRC

Liver progression in cases of doubtfulresectability with non-response to Chemo

Avoids progression of liver metastases CRC progression (rare)

Allows the most appropriatte timing of administration of pelvis Chemo-RDT

Complications of primary CRC requiring urgentor palliative surgery (5-11 %)

Early administration of Chemo Long liver toxicity

Increase S if conversion of M1 toresectables

Small size liver M1 disappearance

Avoids palliative surgery of CRC and itscomplications

Short surgical window (6-12 months)

Sequential liver first (reverse approach): Resection first of all liver metastases and later the CRC. Always neoadjuvant chemo.Rationale 1 : the lesion that kills the patient is the metastasisRationale 2: progression of the CRLM beyond resectability during treatment of the primary tumour, especially if delay is due to complications of primary resection or adjuvant chemotherapy.


Scientific Evidence. Review Simultaneous liver & primary versus sequential

Hillingso JG, Wille-Jorgensen P. Staged or simultaneous resection of synchronous liver metastases from colorectal cancer- a systematic review. Colorectal Disease 2009; 11:3-10

Abelson JS, Michelassi F, Sun T, Mao J, Milsom J, Samstein B, Sedrakyan A, Yeo HL. Simultaneous resection for synchronous colorectal liver metastases : the new standard of care? J Gastrointest Surg 2017; 21: 975-982

Slesser AAP, Simillis C, Goldin R, Brown G, Mudan S, Tekkis PP. A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases. Surgical Oncology 2013; 22: 36-47

Baltatzis M, Chan AK, Jegatheeswaran S, Mason JM, Siriwardena AK.Colorectal cancer with synchronous hepatic metastases: Systematic review of reports comparing synchronous surgery with sequential bowel-first or liver-first approaches. Eur J Surg Oncol 2016; 42: 159-165

Brouquet A, Mortenson MM, Vauthey J-N et al. Surgical Strategies for Synchronous Colorectal Liver Metastases in 156 Consecutive Patients: Classic, Combined or Reverse Strategy? J Am Coll Surg 2010; 210: 934-941

Hillingso JG, Wille-Jorgensen P. Staged or simultaneous resection of synchronous liver metastases from colorectal cancer-a systematic review. Colorectal Disease 2009; 11:3-10

16 studies, 1991 – 2007Biases (prevent meta-analysis):

simultaneous more frequent in right colon Tm and limited resectionssequential more frequent in bigger and multiple M1

Simultaneous surgery Sequential surgery

Length of Hospital Stay √ 15 days 18 days

Morbidity √ 33 % 42 %

Mortality 3.6 % 1 % √Survival = =

Scientific Evidence. Review

Simultaneous liver and primary versus sequential

SequentialColon first

N= 72

SimultaneousColon & Liver

N= 43

SequentialLiver first

N= 27

Morbidity 51 % 47 % 31 % p NS

Mortality 3 % 5 % 4 % p NS

Survival (3, 5 years) 58 %, 48 % 65 %, 55 % 79 %, 39 % p NS

Nº M1 3 1 4 p < 0.05

Major Hepatectomy 66 % 35 % 89 % p< 0.05

Brouquet A, Mortenson MM, Vauthey J-N et al. Surgical Strategies for Synchronous Colorectal Liver Metastases in 156 Consecutive Patients: Classic, Combined or Reverse Strategy?J Am Coll Surg 2010; 210: 934-941

5 % complications related to primary tumour34 % do not complete primary tumour resection

Sequential Liver First


Sequential LIVER FIRST

24 studies, 1991 – 2010: 3159 patients: 1381 Simultaneous (43.7 %) 1778 Sequential (56.3%)

Biases: < Neoadjuvant Chemo in simultaneous More frequent bilobar and bigger M1 in sequential and higher rate of major resections in sequential

Slesser AAP, Simillis C, Goldin R, Brown G, Mudan S, Tekkis PP. A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases . Surgical Oncology 2013; 22: 36-47

Simultaneoussurgery

Sequentialsurgery

Length of Hospital Stay √ 14 days 20 days

Time of surgery = =

Blood loss = 825 ml = 955 ml

Free disease survival = =

Survival = =

Morbidity = 36 % = 37 %



3 studies, 2010 – 2015: 1203 patients: 748 Bowel first (62%)380 Simultaneous (31.5%) 75 Liver first (6.5%)

Minor complications similarMajor complications : 9.1 % (95%CI: 7.6%-10.8%, I2 =48%)Death: 3.1 % (95%CI: 2.2%-4.3%, I2 =0%)5-year survival 44% (I2 =39%)

Overall treatment-related mortality is low and survival is similar among the 3 groups.



Baltatzis M, Chan AK, Jegatheeswaran S, Mason JM, Siriwardena AK.Colorectal cancer with synchronous hepatic metastases: Systematic review of reports comparing synchronous surgery with sequential bowel-first or liver-first approaches. Eur J Surg Oncol 2016; 42: 159-165

135 HospitalsNew York State2005-14

Abelson JS et al. J Gastrointest Surg 2017



Abelson JS et al. J Gastrointest Surg 2017



Sturesson Ch et al. Liver-first strategy for synchronous colorectal liver metastases-an intention-to treat analysis. HBP 2017; 19: 52-58


Classical30 %

Do not complete the planned

treatment(two surgeries)

Liver-first35 %

Do not complete the planned

treatment(two surgeries)

Summary Scientific Evidence

None randomized (RCT) studiesImportant selection biasesSequential in patients with greater liver diseaseNo clear evidence


SIMULTANEOUS vs Sequential BOWEL FIRST vs Sequential LIVER FIRST

Simultaneous and sequential resections are equally feasibleand safe ... ... in selected cases

Simultaneous short length of hospital stay and same survival

Liver first approach is an option in patients with synchronous M1and asymptomatic primary tumour

Despite having greater metastatic disease, same survival as the simultaneous or bowel-first approach

SIMULTANEOUS Surgery

Indications and clinical recommendations

Patients with good general condition who can withstand the 2 procedures (colon and liver)(longer time and greater aggressiveness)

High possibility of R0 resection in both fields(no matter the number, size or location of M1)

Sufficient liver remnant (25-40%) (2 contiguous segments with their vascular pedicles and biliary drainage)

No extrahepatic disease or resectable (pulmonary metastases)

Uncomplicated primary tumor: no occlusion, no perforation, no hemorrhage

Specialized surgeons and estimated surgery times <6 hours (variable)

Do not associate complex surgeries in the two fields

First liver metastases or first colorectal tumor ?

1º liver: Liver surgery without contamination Work with low PVC (<5 mmHg) without affecting this hypovolemia to the colorectal anastomosis Avoid colon edema (on the anastomosis) by Pringle

1º CRC: R0 safety in the primary

Pringle manouvre as short as posible (only if necessary)

SIMULTANEOUS Surgery


During surgery, reevaluate if continue with the 2 procedures (safety)No peritoneal spread No severe complications during the first resectionResection of all metastases seen on intraoperative ultrasound

SEQUENTIAL COLON FIRST Surgery


Patient with comorbidities that prevent 2 simultaneous surgeries

Surgeon who is not an expert in liver surgery

Doubtful resectability (R0) or unresectability of M1 or CCR

Very long estimated surgical time

Complex surgery of the CRC and the M1

Complicated CRC: obstruction, perforation ...

Bilobar metastases, adjacent to large vessels or liver remnant <25-40%

Extrahepatic metastases

SEQUENTIAL LIVER FIRST Surgery


Asymptomatic primary tumor or minimal symptoms (treatable by endoscopy)

Unresectable or borderline resectable liver M1

M1 hepatic and extrahepatic unresectable or doubtfully resectable (initially)

Hepatic M1 of doubtful resectability with uncomplicated primary butdoubtful resectability with oncological criteria

Large or multiple liver M1 at risk of becoming unresectable if they progress after resection of the primary

Vallance AE et al. The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a population-based study of current practice and survival. Colorectal Dis 2018

Synchronous primary CRC and liver metastases

Trends in surgical strategy

Synchronous primary CRC and liver metastases

Surgical resection should include all original sites of M1…when feasible

Management of the disappearing metastases (after chemotherapy)Incidence: 5-38 %MRI more accurate than CT for detecting lesions after chemo

Try to avoid this problemEarly involvement of surgeon: Multidisciplinary boardLimit the duration of chemo: short course or stop when response allow surgical resectionCoils to mark M1 if risk of dissapearing

Ability to detect missing M1 at the time of surgery varies widely: 27-45 %Complete pathological or durable clinical response in 26 % - 82 % of patients (mean= 54%)Complete radiological response IS NOT EQUIVALENT to complete pathological response

Adams RB et al. Selection for hepatic resection of colorectal liver metastases: expert consensus statement. HBP 2013; 15: 91-103Lucidi V et al. Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases. World J Gastroenterol 2016; 22: 3937-3944

When such resections are hazardous, a watch-and-wait strategy can be a reasonable alternative

Simultaneous with primary, sequential bowel-first or liver-first

SELECTIONPatient fitness

Anatomical location: colon, rectum, liverExtent of liver metastases


Complexity of the colorectal tumor

Complexity of liver surgery

Comorbidities of the patient-general condition

Summary

Multidisciplinary BoardOncological and Surgical strategiesSelection of patients for each strategyPlanification for an appropriate sequential treatmentSimultaneous, bowel-first or liver-firstComplex surgical procedures requiring surgical expertise

Synchronous primary and liver metastases

Thank you!!

How to deal with synchronous primary and liver metastases

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