Malignant Ovarian massDr Ajay Aggarwal

MD obs & Gynae

(PGI, Chandigarh)

Ovarian masses approach

• The overall incidence of a symptomatic ovarian cyst in a premenopausal female being malignant is approximately 1:1000 increasing to 3:1000 at the age of 50.

Premenopausal women

• A serum CA-125 assay is not necessary in all premenopausal women when a clear USG diagnosis of a simple ovarian cyst has been made.

• If CA-125 assay is 35-200 units/ml then exclude/treat the common differential diagnoses

• If serum CA-125 assay more than 200 units/ml, discussion with a gynaecological oncologist is recommended

• When CA-125 is raised, serial monitoring of CA-125 may be helpful as rapidly rising levels are more likely to be associated with malignancy than high levels which remain static.

• A pelvic ultrasound is the most effective way to evaluate an ovarian mass with TVS being preferred due to its increased sensitivity.

• Combined use of colour flow mapping and 3D imaging may improve sensitivity, particularly in complex cases.

• Repeating ultrasound assessment in the postmenstrual phase may be helpful in cases of doubt and endometrial views may contribute to diagnosis in cases of estrogen-secreting tumours of the ovary.

• The NICE guideline recommends that for women with suspected ovarian malignancy the RMI I score should be calculated and used to guide the woman’s management.

• RMI = U x M x CA-125.

• RMI I sensitivity 78% (95% CI 71-85%), specificity 87% (95% CI 83-91%)

• There are simple ultrasound rules derived from the IOTA (International ovarian tumor analysis) Group. The use of specific ultrasound morphological findings without CA-125 has been shown to have high sensitivity and specificity.

• Ultrasound rules- benign (B-rules) or malignant (M-Rules).

• Reported sensitivity was 95%, specificity 91%

IOTA Group ultrasound ‘rules’ to classify masses as benign (B-rules) or malignant (M-rules)

B-rules M-rules

Unilocular cysts Irregular solid tumor

Presence of solid component where the largest solid component <7mm

Ascites

Acoustic Shadowing At least four papillary structures

Smooth multilocular tumor with a largest diameter <10cm

Irregular multilocular solid tumor with largest diameter > or equal to 10cm

No blood flow Very strong blood flow

Management

• Women with small (less than 50 mm diameter) simple ovarian cysts generally do not require follow-up as these cysts are very likely to be physiological and almost always resolve within 3 menstrual cycles.

• Women with simple ovarian cysts of 50–70 mm in diameter should have yearly ultrasound follow-up and those with larger simple cysts should be considered for either further imaging (MRI) or surgical intervention.

• Ovarian cysts that persist or increase in size are unlikely to be functional and may warrant surgical management.

• The use of the combined oral contraceptive pill does not promote the resolution of functional ovarian cysts

RCOG, Cochrane

• Aspiration of ovarian cysts- less effective, high recurrence rate, spillage of malignancy

• Laparoscopy- Spillage of cyst contents should be avoided where possible as preoperative and intraoperativeassessment cannot absolutely preclude malignancy.

• Consideration should be given to the use of a tissue bag to avoid peritoneal spill of cystic contents. Any solid content should be removed using an appropriate bag.

• Where possible removal of benign ovarian masses should be via the umbilical port. This results in less postoperative pain and a quicker retrieval time than when using lateral ports of the same size.

Postmenopausal

• It is recommended that ovarian cysts in postmenopausal women should be assessed using CA125 and TVS.

• It is recommended that a ‘risk of malignancy index’ should be used to select those women who require primary surgery in a cancer centre by a gynaecological oncologist.

Ovarian Cancer

• Fifth most common cancer in women

• Lifetime risk of about 2%

• Overall 5-year survival rate of less than 35%

• Patients have advanced disease at diagnosis in more than two thirds of the cases

• About 30% of ovarian neoplasms in postmenopausal women are malignant

• Only about 7% of ovarian epithelial tumors in premenopausal patients are frankly malignant

• Epithelial cancers are the most common ovarian malignancies.

• Peak incidence-56 to 60 years of age

• Types-– serous 75%

– mucinous (20%)

– endometrioid (2%)

– clear cell

– Brenner

– undifferentiated carcinomas

Clinical Approach

• History (Symptoms) and examination

• Investigation- CA-125; AFP & hCG & LDH (<40yrs), CEA

• USG features

• If the ultrasound, serum CA125 and clinical status suggest ovarian cancer, perform a CT scan of the pelvis and abdomen to establish the extent of disease. Include the thorax if clinically indicated.

• Do not use MRI routinely for assessing women with suspected ovarian cancer

• Risk assessment- RMI 1, OVA1, ROMA

OVA 1

• OVA1 is an FDA-approved test for the evaluation of an ovarian mass.

• This new test combines the results of five immunoassays (CA-125, transthyretin, apolipoprotein A1, b2-microglobulin and transferrin).

• Using a unique proprietary algorithm to produce a single numerical score, OVA1 indicates a woman’s likelihood of malignancy.

• It is not a screening test for ovarian cancer, nor is it a replacement for conventional clinical and diagnostic assessments. But OVA1 will improve the accuracy of diagnosis prior to surgery or referral to a gynecologic oncologist.

ROMA

• The Risk of Ovarian Malignancy Algorithm (ROMA) stratifies women at high or low risk for epithelial ovarian cancer based on menopausal status and preoperative serum levels of HE4 and CA-125.

• ROMA had sensitivity 94.3%, vs. 83.7% for RMI

(Gynecol. Oncol. 2009;112:40-6)

• HE4 has sensitivity similar to CA-125 in detecting late-stage disease but greater specificity than CA-125 in diagnosing early ovarian cancer. Validation of HE4 as a diagnostic biomarker in detecting ovarian cancer at early stages is currently ongoing.

CT SCAN

• Role in :

– intra-abdominal disease

– hepatic metastases

– pelvic sidewall ds.

– lymphnode enlargement

– obstructive uropathy,

– possibly an alternate primary cancer site

– role in assessing operability of the tumor.

PET CT scan

• Positron emission tomography (PET) scanning does not have an established role in the diagnosis of primary ovarian malignancy. Its use is still being evaluated, but the PET scan plays a useful role in some patients by detecting the pattern and sites of recurrent disease.

FNAC

• Poor sensitivity

• Spillage and seeding of cancer cells into the peritoneal cavity, thereby changing the stage and prognosis

• ONLY INDICATION :advanced ovarian cancer pts. who are medically unfit to undergo surgery. In these women, malignant cytology confirmed in this fashion will establish a cancer diagnosis, thereby permitting initiation of neoadjuvantchemotherapy

Other modalities in suspected 2⁰ ovarian cancer

• Exclude other primary cancers metastatic to the ovary.

• A barium enema or colonoscopy if symptoms and signs suspicious for colon cancer.

• Stool for occult blood

• Upper gastrointestinal endoscopy if nausea, vomiting, or hematemesis .

• Mammography is indicated if there is any breast mass

• Endometrial biopsy and endocervical curettage if irregular menses or postmenopausal bleeding

Staging

Management of Stage 1

• TAH + BSO with optimal surgical staging - Peritoneal cytology, exploration of pelvis, peritoneal surface, diaphragm, omentum, lymph nodes, biopsy from suspected areas, random biopsies of the pelvic and abdominal peritoneum; and retroperitoneal lymph node assessment , Infracolicomentectomy

• Lymph nodes may be involved in 10 – 20% cases of stage 1

• Perform retroperitoneal lymph node assessment- Lymph node assessment involves sampling of retroperitoneal lymphatic tissue from the paraaortic area and pelvic side walls if there is a palpable abnormality, or random sampling if there is no palpable abnormality.

• Do not include systematic retroperitoneal lymphadenectomy(block dissection of lymph nodes from the pelvic side walls to the level of the renal veins) as part of standard surgical treatment in women with suspected ovarian cancer whose disease appears to be confined to the ovaries (that is, who appear to have stage I disease).

• Do not offer adjuvant chemotherapy to women who have had optimal surgical staging and have low-risk stage I disease (grade 1 or 2, stage Ia or 1b).

• Offer women with high-risk stage I disease (grade 3 or stage Ic) adjuvant chemotherapy consisting of six cycles of carboplatin.

• Discuss the possible benefits and side effects of adjuvant chemotherapy with women who have had suboptimal surgical staging and appear to have stage I disease.

Fertility sparing surgery

• The uterus and the contralateral ovary can be preserved in women with stage Ia, grade 1 to 2 disease who desire to preserve fertility.

• The conditions of the women should be monitored carefully with routine periodic pelvic examinations and determinations of serum CA125 levels.

• Generally, the other ovary and the uterus are removed at the completion of childbearing.

Management of advanced (stage II–IV) ovarian cancer

• Maximal cytoreduction is the most significant predictor of survival.

• If performing surgery for women with ovarian cancer, whether before chemotherapy or after neoadjuvant chemotherapy, the objective should be complete resection of all macroscopic disease.

• The definition of “optimal” debulking is defined as the removal of bulky disease such that the largest single tumor nodule is ≤ 1 cm at the closure of the procedure. ACOG

• Do not offer intraperitoneal chemotherapy to women with ovarian cancer, except as part of a clinical trial.

Interval Debulking Procedures

• Interval debulking surgery is defined as cytoreductive or debulking surgery performed after a course of induction chemotherapy.

– A second surgical attempt, following several rounds of adjuvant chemotherapy, after a suboptimal primary surgery

– Surgery performed after several rounds of neoadjuvantchemotherapy

Role of NACT

• Neoadjuvant Chemotherapy (NACT) followed by primary debulking surgery is an approach that is taken with patients who are considered high-risk surgical candidates.

• The rationale is that giving 2-3 cycles of chemotherapy will reduce the tumor burden and make subsequent surgery more feasible. However, the potential for resistant clones of malignant cells to develop during exposure to NACT remains a concern.

• Prior to giving NACT, the pathologic diagnosis should be confirmed by either fine needle aspiration, CT-guided biopsy. consider laparoscopic biopsy if percutaneous image-guided biopsy is not feasible or has not produced an adequate sample.

• Use cytology if histology is not appropriate

• The advantages of using NACT include:

– Shorter operative times

– Less blood loss

– Reduced time in the ICU

– Shorter hospital stays

Second-Look Surgery

• Second-look surgery either by laparotomy or laparoscopy has been used to reassess the disease status in patients who have completed initial cytoreductive surgery and adjuvant chemotherapy and appear to have had a complete clinical response to treatment (asymptomatic, no radiographic evidence of disease,normal CA 125).

• Surgical reassessment includes examination of both the peritoneal cavity and the retroperitoneal space. Up to 50% of patients with advanced ovarian cancer have evidence of residual disease during surgery despite an apparent clinical remission.

• The presence of disease is associated with a poorer prognosis.

• However, a significant percentage of patients with negative findings will also develop recurrence.

• A clear survival advantage has not been demonstrated for this procedure.

• Routine use of second-look surgery is not recommended and this procedure should therefore generally be reserved for clinical trials.

Epithelial Ovarian Cancer - Prognosis and Recurrent Disease

Five-year survival rates for epithelial ovarian carcinoma by FIGO stage :

• Stage IA - 87%

• Stage IB - 71%

• Stage IC - 79%

• Stage IIA - 67%

• Stage IIB - 55%

• Stage IIC - 57%

• Stage IIIA - 41%

• Stage IIIB - 25%

• Stage IIIC - 23%

• Stage IV - 11%

• Overall survival rate- 35-40%

Recurrent disease

• Approximately 50-60% of women treated for advanced ovarian cancer will experience a relapse of their disease at some point after initial therapy, usually within two years.

• The choice of treatment for recurrent disease is not as clear due to heterogeneity of the:– Time to disease recurrence

– Extent and distribution of recurrent disease

– Performance status of the patient

– Cumulative toxicity from prior treatment

• Chemotherapy: 2nd line agents

• Surgery

• Radiation

Role of frozen section

• The accuracy of frozen-section diagnosis varies from 72% to

88.7%

• Diagnostic accuracy has been shown to be lower in masses

greater than 10 cm (74%) and tumors of low malignant

potential (78%) ACOG 2007

Role of laparoscopy

Potential role of minimally invasive surgery in ovarian cancer is in the following categories:

i) laparoscopic evaluation, diagnosis, and staging of apparent early ovarian cancer

ii) laparoscopic debulking of advanced ovarian cancer

iii) laparoscopic assessment of feasibility of upfront optimal surgical cytoreduction

iv) laparoscopic reassessment in patients with complete remission after primary treatment

v) laparoscopic assessment and cytoreduction of recurrent disease.

laparoscopic evaluation, diagnosis, and staging of apparent early ovarian cancer

• Laparoscopic perioperative benefits- decreased blood loss, faster return of bowel function and shorter hospital stay.

• Laparoscopy may offer an advantage in management of early-stage ovarian cancer by enabling better visualization of difficult areas such as the anterior abdominal wall, subdiaphragmatic areas, peritoneal surfaces, obturator spaces and anterior and posterior cul-de-sacs, as well as magnification and detection of smaller lesions that may be missed at perioperative imaging and even during laparotomy

• Recurrence rates are similar after laparoscopic and open staging procedures, suggesting that the laparoscopic technique does not compromise the outcome of early-stage ovarian carcinoma.

• At present, efforts should be made to reduce the incidence of tumor contamination of the abdominal cavity, including liberal use of a laparoscopic bag and controlled aspiration, and minimizing the risk of cyst rupture.

Minimally Invasive Surgery for Cytoreduction of Advanced Ovarian Cancer

• laparoscopic cytoreduction for primary advanced ovarian cancer can be successful and result in minimal morbidity and acceptable survival

• In 2010, Nezhat et al reported a series of 32 patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who underwent laparoscopic debulking. In 17 of the 32 patients, the disease was successfully debulked at laparoscopy, with 88% of optimal cytoreduction. At mean follow up of 19.2 months, 9 patients were without evidence of the disease. Compared with the group who underwent laparotomy, the laparoscopic approach had resulted in minimal blood loss and a shorter hospital stay. No patients developed port-site metastasis, and time to disease recurrence in the laparoscopic group was not inferior to that in the laparotomy group.

• In another retrospective series of 25 patients with presumed stage III/IV primary ovarian cancer undergoing laparoscopic assisted cytoreduction, Fanning et al (2011) reported successful cytoreduction in 23 patients (92%). Two procedures were converted to laparotomy because of extensive omentaldisease and bulky metastasis surrounding the rectosigmoidcolon, respectively. In all 25 patients, the lesion was cytoreduced to <2 cm, and 36% had no residual disease. Median operative time was 2.3 hours, and blood loss was 340 mL. Median length of stay was 1 day. Median visual analog scale pain score was 4, which was discomforting. Six patients (24%) had postoperative complications; however, none were grade 3 or 4. Median overall survival was 3.5 years.

Retrospective case-control studyMagrina et al [2011]

Robotic surgery Laparoscopy laparotomy

Number of subjects 25 27 119

stage 3&4 Ca ovary 60% 75% 87%

Mean Blood LossP<0.001

164 mL 267 mL 1307 mL

length of hospital stay p <.001

4 days 3 9

Node counts same

Operative time(p 5 .009)

315minutes 254 261

SurvivalP=.08 same

67.1% 75.6% 66.0%

Complications same

• The authors concluded that in patients undergoing primary tumor excision of epithelial ovarian cancer alone or with 1 additional major surgery, robotic-assisted and laparoscopy are preferable to laparotomy. overall survival is not influenced by the type of surgical approach but by the extent of debulking(complete vs incomplete)

Laparoscopic Assessment of Feasibility of Upfront Optimal Surgical Cytoreduction

• In selected cases in which neoadjuvant triage is offered to patients and the disease after completion of chemotherapy is less extensive, laparoscopic debulking surgery may be performed.

Laparoscopic Reassessment or Second-Look Surgery

• Today this procedure is performed primarily in clinical trials or in selected cases with uncertain clinical response of patients.

• Disease recurrence after negative second-look surgery was reported to be similar for laparoscopy and laparotomy

Laparoscopic Assessment and Cytoreduction ofRecurrent Disease

• The role of secondary cytoreduction surgery to treat recurrent ovarian carcinoma is debatable.

• several authors have suggested some criteria including isolated recurrence, lack of ascites and optimal debulking at the primary surgery as indications for secondary debulking.

• In these selected cases, laparoscopic secondary cytoreductionhas been reported in case reports and series, with acceptable results insofar as efficacy and outcomes are concerned.

• laparoscopic debulking using the loop electrosurgical excision procedure and argon beam coagulation seems feasible (94%), successful (94%), and safe (complications in 6%)

Trinh et al 2004

• In a well-selected population, laparoscopy is technically feasible and can be used for optimal cytoreduction in patients with recurrent ovarian, fallopian, or primary peritoneal cancer

Nezhat et al 2012

Specific points

• Any suspect growth is biopsied.

• In the case of normal visual exploration, random peritoneal biopsies are performed in the pouch of Douglas, pelvic and abdominal parietal peritoneum, paracolic gutters, hemidiaphragms and mesentery.

• When conservative treatment is considered, biopsy of the contralateral ovary is performed only in the case of suspect growth on imaging studies or at laparoscopy. Dilation and curettage are performed so as not to miss a possible endometrial spread or a synchronous tumor

• Removal of the specimen exclusively using a laparoscopic bag and control of the bag integrity once extracted

Thanks

• This powerpoint presentation was presented by Dr Ajay Aggarwal under moderation of Dr Nikita Trehanon 04/03/2015 at 12:30pm indian time and 11am Dubai time. It was a video conference between Sunrise Hospital, Delhi and International modern Hospital, Dubai. There was a discussion after presentation and few points were highlighted.

• Management of simple and complex adnexal mass was discussed. And guidelines were explained.

• For risk assessment, role of RMI and ROMA scores were discussed and utility of ROMA score with high sensitivity and equal efficacy was explained.

• Ultrasound findings to differentiate benign from malignant masses as suggested by IOTA group were also explained.

• FIGO staging of ovarian cancer was changed in 2014 and it was discussed during the presentation. Role of new staging is in prognosis.

FIGO Ovarian Cancer Staging Effective Jan. 1, 2014

FIGO Ovarian Cancer Staging Effective Jan. 1, 2014

FIGO Ovarian Cancer Staging Effective Jan. 1, 2014

• Other major recommendations are as follows:

• Histologic type including grading should be designated at staging

• Primary site (ovary, Fallopian tube or peritoneum) should be designated where possible

• Tumors that may otherwise qualify for stage I but involved with dense adhesions justify upgrading to stage II if tumor cells are histologically proven to be present in the adhesions

• Role of chemotherapy, lymph node assessment versus lymphadenectomy and role of fertility sparing surgery were discussed with respect to different stages of ovarian cancer.

• The session was finished with discussion of role of minimal invasive surgery (laparoscopic surgery) in early and advanced ovarian cancer and recurrence cases as well.