Page 18 of 37

OG34.2 | Ovarian Cancer — SDL Guide (Part 3)

Chemotherapy and Targeted Therapy

Ovarian cancer is one of the more chemosensitive solid tumours, and adjuvant or primary systemic chemotherapy is central to management of all but the earliest-stage disease. The choice of regimen depends on histological type, stage, and molecular profile.

For epithelial ovarian cancer, the current standard first-line regimen is carboplatin (AUC 5–6) + paclitaxel (175 mg/m²) every 3 weeks for 6 cycles (established by GOG 111 and OV10 trials replacing the older cisplatin+cyclophosphamide). Carboplatin is preferred over cisplatin in most settings because of comparable efficacy with a more favourable toxicity profile (less nephrotoxicity, neurotoxicity, nausea). Intraperitoneal (IP) chemotherapy delivers high drug concentrations directly to the peritoneal surface and has shown survival benefit in optimally debulked Stage III disease (GOG 172), but its toxicity and catheter-related complications have limited widespread adoption.

Bevacizumab (anti-VEGF monoclonal antibody) added to first-line carboplatin-paclitaxel and continued as maintenance has demonstrated a modest progression-free survival benefit (ICON7, GOG 218 trials), particularly in Stage IIIB–IV disease. It is not approved universally in resource-limited settings due to cost.

The most significant advance in ovarian cancer treatment is PARP inhibitor maintenance therapy for BRCA1/2-mutated advanced epithelial ovarian cancer. Olaparib (SOLO-1 trial) and niraparib (PRIMA trial) as maintenance after complete or partial response to first-line chemotherapy have markedly prolonged progression-free survival in patients with BRCA mutations or homologous recombination deficiency (HRD). All women with advanced epithelial ovarian cancer should be tested for germline and somatic BRCA mutations.

For germ cell tumours, the standard chemotherapy is BEP (bleomycin + etoposide + cisplatin) for 3–4 cycles, which achieves cure rates >95% even in advanced dysgerminoma and excellent outcomes in other germ cell types. Response is monitored by serial AFP, β-hCG, and LDH normalisation. Dysgerminoma is also radiosensitive, though chemotherapy is preferred to preserve fertility.

For sex-cord stromal tumours such as granulosa cell tumours, adjuvant chemotherapy (carboplatin + paclitaxel or BEP) is reserved for Stage IC and above. Surveillance with serum inhibin is used to detect recurrence, which can occur decades after initial treatment.

For platinum-resistant relapse (progression within 6 months of platinum completion), liposomal doxorubicin, topotecan, or gemcitabine are used. Platinum-sensitive relapse (>6 months after platinum) is re-treated with platinum-based combinations. PARP inhibitors also have a role in BRCA-mutated relapsed disease.

Provided image

Prognosis and Surveillance

Prognosis in ovarian cancer is predominantly stage-driven, with histological type, grade, and residual tumour burden also contributing significantly. The outcome gap between early and advanced disease is wider for ovarian cancer than for almost any other gynaecological malignancy — a woman diagnosed at Stage IA has a greater than 90% chance of long-term survival, while a woman diagnosed at Stage IIIC has less than a 40% chance even with optimal treatment. This stark disparity explains why the absence of an effective screening programme is such a public health concern: by the time symptoms bring a woman to clinical attention, she is usually already in the advanced-stage group. Within advanced-stage disease, the quality of surgical cytoreduction is itself a prognostic modifier — a woman achieving complete cytoreduction (R0) at staging laparotomy has meaningfully better outcomes than one with residual disease, even within the same FIGO stage. This means that the surgical team's decisions in the operating theatre directly affect long-term survival. The 5-year overall survival rates by FIGO stage (approximate values from pooled international data):
- Stage I: ~85–93% (IA > IB > IC; IC3 somewhat worse)
- Stage II: ~70–75%
- Stage III: ~20–40% (IIIA1 better than IIIC; R0 debulking improves survival within stage)
- Stage IV: ~15–20%

Histological type modifies the prognosis within stage: clear cell carcinoma has worse stage-for-stage prognosis than serous carcinoma; mucinous carcinoma is often chemoresistant at advanced stage. Germ cell tumours (particularly dysgerminoma) have an excellent prognosis even at advanced stage due to chemosensitivity. Granulosa cell tumours have an indolent course but are notable for very late recurrence — surveillance must be lifelong.

Post-treatment surveillance follows a structured protocol. CA-125 is measured every 3 months for the first 2 years, then every 6 months for 3 years, then annually. A rising CA-125 (confirmed on two readings, 2 weeks apart) precedes clinical or radiological relapse by a median of 3–5 months ('lead time'). However, the ICON4 trial found that treating CA-125-only relapse without clinical symptoms did not improve survival over waiting for symptomatic relapse — the current approach is to use a rising CA-125 to prompt CT scanning and clinical review, not automatic chemotherapy re-initiation. CT abdomen/pelvis is the standard imaging at suspected relapse.

Second-look laparotomy (surgical re-exploration after completing chemotherapy to assess pathological complete response in clinically responding patients) was practiced in the 1980s–1990s but has been abandoned — it did not improve overall survival in randomised trials.

Genetic counselling and cascade testing: All women diagnosed with epithelial ovarian cancer (especially serous and endometrioid types under age 70, and all clear-cell and mucinous at any age) should be offered germline BRCA1/2 and mismatch repair gene (Lynch syndrome) testing. Positive results enable cascade genetic testing of first-degree relatives, allowing risk-reducing interventions including RRSO and enhanced breast surveillance in BRCA carriers.

Provided image