Role of surgery in the management of Ovarian cancer. Waseem Kamran Sub-speciality Fellow Surgical Gynaecological Oncology St James Hospital

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1 Role of surgery in the management of Ovarian cancer Waseem Kamran Sub-speciality Fellow Surgical Gynaecological Oncology St James Hospital

2 Role of surgery Prevention Diagnosis Staging Treatment Palliative

3 Prevention surgery-rrso Gene Mutation BRCA1 BRCA2 (Up to 60%).

4 Diagnosis Ovarian cystic mass > 5cm; no regression for 6-8 weeks Solid ovarian lesion Any ovarian lesion with papillary vegetations on cyst wall (TVUS) Any adnexal mass > 10 cm Ascites Palpable adnexal mass in prepubertal/postmen-pausal Torsion / Rupture suspected

5 Types of Surgery-1 Staging Surgery A thorough exploration to assess the extent of disease % of presumed early cancers have occult peritoneal and lymphatic metastasis Primary cytoreduction Refers to the initial surgical excision of tumour and tumour involved organs prior to chemotherapy. Optimal surgical cytoreduction is defined as residual tumour less than 1 cm.

6 Types of Surgery-2 Interval cytoreduction surgery Cytoreduction on patients who have previously received neoadjuvant chemotherapy. Second look Surgery refers to the surgical management of recurrent ovarian cancer Surgery for bowel obstruction

7 Staging Procedure-1 Vertical midline laparotomy Thorough examination of abdominal viscera Quantify the disease Peritoneal washings, biopsies Frozen sections Systemic lymph adenectomy

8 Staging Procedure-2 Early stage cancer Examination with systemic lymphadenectomy 1 in 4 early stage cancers get upstaged to IIIC (Maggioni A, 2006) Advanced stage cancer Role of systematic lymphadenectomy is unclear Not a prognostic factor No correlation between nodal status and survival (Parazzini F, 1999) increased progression-free survival compared to the no lymphadenectomy arm: 31.2% vs 21.6% (Panici PB, 2005)

9 Primary Cytoreduction-1 Cornerstone of the initial surgical management Indicated in patient deemed suitable for optimal cytoreduction (less than 1cm residual disease, GOG) Careful selection of patients Performace status Nutrition status Medical co-morbidities Impending bowel obstruction

10 Primary cytoreduction-2 Optimal cytoreduction Controversial definition: No prospective randomized control trials to define the degree of residual disease that has the best clinical outcome. GOG: <1cm Disease > 1.5 cm: poor prognostic indicator (Griffi ths CT, 1975, 1979)

11 Primary cytoreduction-3 Confined to the pelvis: TAH, BSO Appendectomy, ± bowel resection Omentectomy Pelvic and para-aortic lymph adenectomy Conservative surgery (Fertility saving) Upper abdominal disease May also include spleenectomy, nephrectomy, cholecystectomy, hepatic and diaphram resection etc

12 Primary cytoreduction-4 Volume of residual disease inversely correlates with survival (Bristow RE, Hoskins WJ, Eisenkop SM et al) No residual disease shows improved overall survival and progression-free survival. Chi et al, 2006 reported the following median overall survival rates Size NVD <5mm 0.6-1cm 1-2cm >2cm Survival (months)

13 Primary cytoreduction-5 Improves symptoms bloating, abdominal distention, or abdominal pain Often involves aggressive surgery High peri-operative morbidity May delay subsequent chemo-therapy

14 Sub-optimal debulking-1 Optimal debulking is not always feasible Limiting factors: Extensive upper abdominal Retroperitoneal disease Large tumor burden in bowel Mesentery, or porta hepatis.

15 Sub-optimal debulking-2 Selection criteria often used to determine which patients cannot be optimally cytoreduced Include presence of stage IV disease, massive ascites, bulky omental disease, splenic involvement, and suprarenal lymphadenopathy If optimal debulking not possible, then the operation is generally limited to a TAH & BSO and/or omentectomy

16 Sub-optimal debulking-3 Clinical models : Computed tomography (CT) scans have been evaluated to determine their predictivevalue in identifying unresectable disease ( Nelson et al) Not very accurate Do not consider tumour biology and surgeon s expertise Decision largely remains clinical

17 Sub-optimal debulking-4 The majority of women will receive adjuvant chemotherapy after suboptimal debulking Role of subsequent attempt of debulking surgery is unclear Survival benefit results contradictory Burg et al, 1995 (EORTC trial): improved survival ( 26 vs 20 months) Rose PG (GOG 152 trial), 2004: No difference in PFS or overall survival (32 vs 33 months)

18 Interval cytoreduction surgery-1 Patients with massive ascites, large bilateral pleural effusions, extensive upper abdomen and retroperitoneal lymphadenopathy may benefit from neoadjuvant chemotherapy Patients with favourable response to chemotherapy and improved performance and nutritional status are considered for interval debulking surgery.

19 Interval cytoreduction surgery-2 In numerous retrospective and prospective case-control studies interval debulking has shown to be associated with decreased morbidity when compared to initial cytoreductive surgery in advanced ovarian cancer Overall survival rates are similar (Primary Vs Interval cytoreduction) Results of a randomized control study, Chemotherapy or Upfront Surgery (CHORUS) awaited

20 Role of minimally invasive surgery-1 Feasible for early ovarian cancer In assessing resectability of advanced disease prior to laparotomy In second-look procedures. Decreased morbidity and shorter hospitalization Operative time of 120 to 240 minutes has been reported with laparoscopic staging of ovarian cancer

21 Role of minimally invasive surgery-2 Complications include vascular and gastrointestinal injuries. Formation of port site metastases, particularly in the setting of carcinomatosis. Rupture and dissemination of the contents (15-25%)

22 Second look surgery Either laparotomy or laparoscopy To determine the disease status in an asymptomatic patient who has no clinical evidence off disease and has completed the planned number of chemotherapy cycles To determine end point for chemotherapy The value in laparoscopy lies mostly in its positive predictive value If unresectable disease: laparotomy can be avoided If negative: Laparotomy may be undertaken

23 Secondary cytoreduction surgery-1 May be performed in some cases of disease recurrence Limited data regarding the benefits of secondary cytoreductive surgery Secondary cytoreduction may be considered in subgroup With progression-free interval of 12 to 18 months from completion of adjuvant chemotherapy Localized recurrence Amenable to complete cytoreduction in potentially chemosensitive disease Good performance status

24 Secondary cytoreduction surgery-2 Aim is complete cytoreduction Patients with optimal secondary cytoreduction (< 1 cm) survived for 16 to 60 months, compared to 8 to 27 months for those patients with residual diseases 1 cm (Tebes SJ, 2007; Santillan A, 2007; Benedetti Panici P, 2007) As with primary surgery, the biology of the cancer is an important confounding factor.

25 Surgery for bowel obstruction-1 Some patients with recurrent ovarian cancer will develop small and/or large bowel obstruction Patients are often end-stage and malnourished, with substantial chemoresistant tumour burden Palliative surgery is controversial and requires skilled patient selection Multifactorial: Mechanical blockage include Dense mesenteric infiltration, carcinomatosis, and adhesions.

26 Surgery for bowel obstruction-2 Possible palliative procedures: Bowel resection, colostomy, or intestinal bypass or gastrostomy tube Re-obstruction rate is 10-50% Factors associated with successful palliation include absence of the following (Jong et al, 1995): 3 litres of ascites, multifocal obstruction, palpable bulky tumour, and preoperative weight loss 9 kg.

27 Conclusion Despite significant progress in chemotherapy and biologic therapy, surgery remains an important modality in the treatment of ovarian cancer Despite the benefits of surgical intervention, the specific biology of a patient s disease is central to her response to chemotherapy, duration of remission, and ultimate survival.

28 Thank You