Surgery plays a central role in the management of advanced ovarian cancer (FIGO stage III/IV), serving as a cornerstone of treatment alongside systemic chemotherapy.
The primary surgical goal is maximal cytoreduction—ideally achieving no visible residual disease (R0 resection), or at minimum reducing tumor burden to less than 1 cm of residual disease.
The extent of cytoreduction achieved during surgery remains one of the most important independent prognostic factors for overall survival in patients with advanced epithelial ovarian cancer (EOC).
Primary cytoreductive surgery involves performing maximal tumor debulking before initiating systemic chemotherapy.
This approach has traditionally been the standard of care for patients with advanced ovarian cancer.
Primary cytoreductive surgery may offer survival advantage in patients with less extensive disease
Allows immediate tumor reduction in selected patients, and provides complete pathologic diagnosis and staging information.
Primary cytoreductive surgery can carry significant morbidity, especially in patients with high tumor burden or poor performance status.
Primary cytoreductive surgery may delay or preclude postoperative chemotherapy if complications occur.
Primary cytoreductive surgery requires careful patient selection to maximize benefit and minimize risk.
Neoadjuvant chemotherapy involves administering 3-4 cycles of platinum-based chemotherapy before attempting surgical cytoreduction is referred to as interval debulking surgery.
Advantages of perioperative chemotherapy:
Reduced perioperative complications compared to primary cytoreductive surgery. Lower perioperative morbidity and mortality May improve likelihood of achieving complete cytoreduction in patients with initially unresectable disease Better tolerated in patients with poor performance status or significant comorbidities
Four randomized controlled trials have evaluated the efficacy of neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) with mixed results:
EORTC and CHORUS trials-Demonstrated noninferiority of NACT compared with PDS in terms of progression-free survival (PFS) and overall survival (OS)
SCORPION trial-Compared PDS with NACT in 171 patients with stage IIIC/IV disease.
After median follow-up of 42 months, NACT was not shown to be superior to PDS
Japanese Gynecologic Oncology Group -A multicenter phase 3 noninferiority trial that failed to demonstrate noninferiority of NACT
These trial results stand in contrast to multiple retrospective studies demonstrating markedly longer PFS and OS with PDS.
For example, in a cohort of 568 patients with stage III disease, patients who underwent PDS had a median OS of 71.7 months compared to 42.9 months in those who underwent NACT.
The decision between primary cytoreductive surgery and neoadjuvant chemotherapy followed by interval cytoreductive surgery should be individualized based on multiple factors:
Performance status (ECOG/Karnofsky scores) Age (patients >75 years may be triaged to NACT) Comorbidities and American Society of Anesthesiologists (ASA) classification Nutritional status (serum albumin <3.5 g/dL may indicate NACT preference) Patient preferences regarding treatment approach and trade-offs Tumor burden and distribution Likelihood of achieving optimal/complete cytoreduction Presence of extensive upper abdominal disease Tumor biology and histology
Center volume and experience with complex cytoreductive procedures
The volume of residual disease following debulking surgery is one of the most important prognostic factors for overall survival in ovarian cancer.
Optimal cytoreduction is associated with improved survival, while suboptimal debulking (>1 cm residual disease) is consistently linked to worse outcomes.
Complete gross resection (R0)-Best survival outcomes
Optimal cytoreduction (<1 cm residual)-Intermediate outcomes Suboptimal cytoreduction (>1 cm residual)-Poorest outcomes
The greatest survival benefit is seen when complete gross resection (CGR) is achieved, regardless of whether surgery is performed in the primary or interval setting.
Patients who achieve complete cytoreduction have significantly improved survival compared to those with any residual disease.
The Gynecologic Oncology Group (GOG) 172 trial, a randomized phase 3 clinical trial evaluating intraperitoneal chemotherapy in patients with stage III epithelial or primary peritoneal carcinoma at the time of PDS, required patients to have undergone optimal resection with residual disease ≤1 cm: progression-free survival was 18.3 months and overall survival was 49.7 months.
High-volume centers have consistently reported substantially longer survival outcomes, highlighting the importance of surgical expertise and center experience in achieving optimal results.
Achieving complete gross resection often requires extensive procedures that may include resection of disease in multiple anatomic sites.
Common Procedures Required:
Total hysterectomy and bilateral salpingo-oophorectomy Omentectomy Peritoneal stripping (pelvic and abdominal) Bowel resection (required in approximately 32% of interval debulking cases) Upper abdominal procedures (required in approximately 51% of interval debulking cases): Diaphragm stripping or resection Splenectomy Dissection of the porta hepatis Liver resection Distal pancreatectomy Pelvic and para-aortic lymph node evaluation
Role of Lymphadenectomy
The LION trial evaluated the role of systematic lymphadenectomy at the time of PDS in women who had normal-appearing lymph nodes preoperatively and intraoperatively: systematic lymph node dissection (LND) adds no survival benefit and entails greater morbidity.
Routine pelvic and para-aortic lymphadenectomy is not indicated unless lymph nodes are clinically enlarged or suspicious for metastatic involvement.
Selective removal of bulky or suspicious nodes remains appropriate.
Diagnostic laparoscopy can serve as a valuable tool to help identify candidates most likely to benefit from primary surgery versus those who should receive neoadjuvant chemotherapy.
Diagnostic laparoscopy assessment can:
Evaluate extent and distribution of disease Assess resectability before committing to laparotomy Maximize rates of optimal tumor removal Decrease rates of futile laparotomy
A retrospective cohort study identified 3,071 patients with stage IIIC-IV ovarian cancer treated with NACT and IDS, No difference was found in 3-year survival between patients treated with MIS versus laparotomy (47.5 vs 52.6 months).
Patients undergoing MIS were more likely to undergo excision of only gynecologic structures without additional cytoreductive procedures.
MIS patients likely represented a group with lesser disease burden
In one retrospective review, no patients undergoing MIS had hepatic resection or gastrointestinal resection
The goal of surgery must remain complete gross resection regardless of the surgical approach chosen.
Complex upper abdominal procedures may not be feasible via minimally invasive approach.
Oncologic outcomes must not be compromised in pursuit of minimally invasive technique.
To date, no level 1 evidence exists comparing MIS with traditional laparotomy in the setting of debulking surgery for EOC.
In the recurrent setting, secondary cytoreductive surgery may be considered for select patients with platinum-sensitive disease and a high likelihood of achieving complete resection.
The benefit is limited to those in whom complete gross resection is feasible, and the decision must be carefully balanced against surgical risks and evolving systemic therapy options.
Disease-free interval is an important prognostic factor for overall survival after secondary cytoreduction surgery (SCS).
Overall survival is significantly prolonged when complete resection is achieved at second surgery.
In a large retrospective series investigating the effect of SCS in 626 patients with recurrent platinum-sensitive ovarian cancer found:
Median OS: 54 months with SCS versus 33 months with chemotherapy alone
SCS has been shown to be safe and feasible for selected patients with recurrent platinum-sensitive EOC when performed at experienced centers with appropriate patient selection.
Careful patient selection is critical for secondary cytoreduction, candidates include:
Platinum-sensitive recurrent disease (typically ≥6 months from last platinum therapy) Good performance status Limited number of recurrence sites High likelihood of achieving complete gross resection Adequate disease-free interval from prior surgery No evidence of rapidly progressive disease
A landmark phase 3 multicenter randomized controlled trial evaluated the use of hyperthermic intraperitoneal chemotherapy at the time of interval debulking surgery versus IDS alone.
Newly diagnosed stage III EOC All patients received NACT owing to extensive abdominal disease Not eligible for PDS Randomized 1:1 at time of surgery if CGR or optimal resection was anticipated Primary endpoint: Recurrence-free survival (RFS)
RFS improved in HIPEC arm: median HR 0.66 OS improved in HIPEC arm: HR 0.67 No difference in rates of serious postoperative adverse events.
HIPEC at the time of interval debulking surgery is now listed as an option in the guidelines for the primary management of EOC.
HIPEC at Secondary Cytoreduction
Interest continues in the role of HIPEC at the time of secondary cytoreductive surgery for recurrent EOC.
A large retrospective series of 249 patients with persistent or recurrent EOC treated with debulking surgery and HIPEC showed:
Optimal resection achieved in 92.2% Excellent outcomes in sub-cohort of 184 patients with platinum-sensitive disease Median OS: 52 months
A phase 2 RCT presented by Zivanovic and colleagues at the 2020 ASCO annual meeting showed no significant difference in PFS or OS in patients with platinum-sensitive recurrent disease who underwent SCS with or without HIPEC (agent: carboplatin)
As management options for patients with advanced EOC become more complex, their preferences regarding trade-offs between survival benefits and quality of life must be incorporated into trial outcomes and individualized treatment planning.
The standard treatment for a patient with newly diagnosed epithelial ovarian cancer consists of:
Surgical debulking (primary or interval) Platinum/taxane chemotherapy (typically carboplatin and paclitaxel for 6 cycles)
Maintenance therapy with agents such as:
Poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, niraparib, rucaparib)
Bevacizumab (anti-VEGF antibody)
Or combination approaches based on molecular characteristics
The integration and sequencing of these treatment modalities should be individualized based on patient factors, disease characteristics, and molecular features.
Currently, no universal consensus exists to definitively guide the choice between neoadjuvant chemotherapy and primary debulking surgery.
With both PDS and NACT/IDS, the best outcomes are achieved in patients who have complete gross resection.
The fundamental goal—maximal cytoreduction—remains paramount regardless of timing.
High-volume centers consistently report better outcomes, likely reflecting:
Greater surgical expertise Experience with complex procedures Multidisciplinary care coordination Better patient selection Improved perioperative management
Surgery remains a cornerstone of advanced ovarian cancer management, with the extent of cytoreduction being the key determinant of outcome.
Complete gross resection (R0 resection) represents the most important modifiable prognostic factor and should remain the goal regardless of whether surgery is performed in the primary or interval setting.
Residual disease following debulking surgery remains the most important modifiable factor affecting survival.