Management of stage III and IV ovarian cancer, characterized by extensive peritoneal dissemination or distant metastasis, focuses on maximizing surgical cytoreduction and systemic therapy to improve survival outcomes. Post-surgical management includes platinum-based chemotherapy, typically combining carboplatin and paclitaxel for six cycles and often a decision about maintenance therapy (see section 4.3 Maintenance therapy).

Pre-operative chemotherapy is appropriate for selected patients with advanced and biopsy-proven ovarian/fallopian tube/primary peritoneal malignancy who are not appropriate for immediate maximal debulking. The decision to delay surgery should be made following consultation with a gynecologic oncologist, in a multidisciplinary team setting (see sections 3 Surgery and 3.4 Delayed Primary Debulking).  We recommend routine monitoring of CA125 or other relevant marker with each cycle, and that patients are referred back to  Gynecologic Oncology (surgeon) after 2-3 cycles to be evaluated for delayed debulking surgery and to arrange timely care. A CT chest/abdomen/pelvis should be performed prior to the assessment by the Gynecologic Oncologist to determine response to chemotherapy and the distribution of disease.  If the chemotherapy has reduced the burden of disease, the distribution is accessible, and the patient’s performance status is satisfactory, then surgery is usually planned post cycle 3 or 4. If there is progressive disease on pre-operative chemotherapy, there is generally no role for surgery, except for bowel or ureteric obstruction. Generally, total number of chemotherapy cycles is 6. Historically, at least 2 additional cycles were given after delayed primary debulking, thus sometimes exceeding 6 cycles, however, currently, with the use of maintenance therapy (see section 4.3 Maintenance therapy) chemotherapy treatment is often completed with cycle 6. Ultimately, the number and timing of cycles will depend on disease status, patient preference and physician preference. There are no data to demonstrate improved patient outcomes beyond 6 cycles of standard chemotherapy. 

Timing of initiation of post-operative chemotherapy: Treatment should be started as soon as it is felt safe to do so after surgery, with the goal of completing 6 cycles of chemotherapy in total, when possible. For most patients who have an uncomplicated post-operative course, this is often safe and feasible within 14-21 days of the operation. Early treatment initiation prevents the re-accumulation of ascites and is not associated with delays in surgical healing or post-operative complications. Randomized data are not available to define the optimal interval of time for treatment initiation, but retrospective analyses show worse prognosis when treatment delays are excessive.  

Maintenance therapy has shown to improve progression-free survival (PFS) and in some cases impact overall survival and is often recommended for stage III and IV disease - see below (section 4.3 Maintenance therapy).  

In recurrent disease, treatment is guided by the platinum-free interval, with platinum-sensitive recurrences favoring re-treatment with platinum-based regimens, potentially combined with PARP inhibitors or bevacizumab. Ongoing research is focused on optimizing therapeutic combinations and sequencing to enhance overall survival and quality of life.

Note: The final treatment decision should be made in consultation with an oncologist, considering individual patient factors and eligibility criteria.

*For patients with stage III or IV high grade serous ovarian carcinomas treated with pre-operative carboplatin – paclitaxel regimen (every 3 weeks or weekly) in first-line setting. A minimum of 3 values of CA-125 within 100 days are required, starting with Cycle 1 day 1 . https://www.biomarker-kinetics.org/CA-125-neo

1Olaparib GOOVFOLAM Protocol up to 2 yrs of therapy (patients with partial response who are still deriving benefit from olaparib at 2 years may be considered for extension of therapy). 

2Niraparib GOOVFNIRM Protocol up to 3 yrs of therapy.

3Bevacizumab GOOVCATB Protocol up a maximum of 17 total doses of bevacizumab. 

Most patients being diagnosed with EOC today will have been exposed to a PARP inhibitor during first-line therapy. However, some patients (e.g., initially diagnosed with stage I or II disease, or had first-line treatment before maintenance therapy for advanced disease was routinely available) may have disease recurrence and for them, maintenance therapy may be considered once chemotherapy is completed. 

The pivotal NOVA trial demonstrated that niraparib significantly prolonged progression-free survival (PFS) in both BRCA-mutated and non-BRCA patients with recurrent platinum-sensitive (recurrence > 6 months from the time of the last platinum-based therapy) and platinum-responsive (evidence of response to the last line of platinum-based therapy) ovarian cancer [35]. There was no improvement in overall survival The SOLO2/ENGOT-Ov21 trial further established the efficacy of olaparib in BRCA-mutated recurrent ovarian cancer, showing a significant improvement in PFS and overall survival (OS) compared to placebo [36].