Ovarian Cancer

The "silent killer" — subtle presentation, BRCA-mediated risk, platinum-based treatment, and PARP inhibitor maintenance strategies

Key Points

Epidemiology & Incidence

Ovarian cancer is the fifth leading cause of cancer death in women in the US. In 2024, approximately 19,680 new cases and 12,740 deaths were projected. The overall 5-year survival rate is only ~50%, largely because ~75% of cases are diagnosed at stage III or IV due to the absence of effective screening and the nonspecific nature of early symptoms. The majority of ovarian cancers (~90%) are epithelial in origin. Major histologic subtypes include: high-grade serous (HGSC, ~70% — the most lethal), low-grade serous, endometrioid, mucinous, and clear cell carcinomas. Non-epithelial cancers…

Genetic Predispositions & Risk Factors

Hereditary factors account for approximately 20–25% of ovarian cancers: • BRCA1 mutations: 35–46% lifetime ovarian cancer risk (population risk: 1.3%). BRCA1-associated ovarian cancer typically presents a decade earlier than sporadic cases. • BRCA2 mutations: 13–23% lifetime ovarian cancer risk; associated with better platinum sensitivity and improved prognosis vs. BRCA1. • Lynch syndrome (MMR gene mutations): 6–13% lifetime endometrial cancer risk; 3–14% ovarian cancer risk depending on gene. MLH1 and MSH2 carry higher risk than MSH6 and PMS2. • BRIP1, RAD51C, RAD51D: Moderate-penetrance HR…

Clinical Presentation

Ovarian cancer is notorious for nonspecific, subtle early symptoms — often dismissed by patients and clinicians — and for presenting at advanced stage when the abdomen and peritoneum are widely involved. Early/localized symptoms (Stage I–II): • Pelvic pressure or pain • Unilateral adnexal mass found incidentally on pelvic exam or imaging • Early satiety or bloating (may indicate small omental/peritoneal disease) • Urinary urgency or frequency (from pelvic mass effect) Advanced disease symptoms (Stage III–IV): • Increasing abdominal distension (from ascites — malignant peritoneal implants…

Staging Overview

Ovarian cancer is staged surgically using FIGO 2014 / AJCC 8th Edition: Stage I: Confined to ovary(ies) or fallopian tube(s) • IA: One ovary/tube, capsule intact, no malignant ascites • IB: Both ovaries/tubes, capsule intact • IC: Ruptured capsule (IC1), malignant cells in peritoneal washings (IC2), or malignant ascites (IC3) Stage II: Extends to pelvic organs • IIA: Involves uterus or tubes • IIB: Other pelvic organs Stage III: Peritoneal metastases beyond pelvis ± retroperitoneal lymph node metastases • IIIA1: Lymph node metastases only • IIIA2: Microscopic peritoneal metastases above…

Stage I–II Treatment

Stage I ovarian cancer has a much more favorable prognosis — 5-year survival exceeds 90% for stage IA/IB, grade 1–2. Surgical staging: Comprehensive surgical staging is essential and includes: total abdominal hysterectomy (TAH) + bilateral salpingo-oophorectomy (BSO), omentectomy, peritoneal biopsies (bilateral paracolic gutters, pelvic peritoneum, diaphragm), pelvic + para-aortic lymph node dissection, and peritoneal washings. Understaging is common without systematic staging and understaged disease is undertreated. Fertility-sparing surgery (unilateral salpingo-oophorectomy without…

Stage III–IV Treatment & PARP Inhibitor Maintenance

Advanced ovarian cancer (stage III–IV) is treated with a combination of surgery and platinum-based chemotherapy followed by maintenance therapy. Primary cytoreductive surgery (PCS): Upfront surgical debulking with intent to achieve R0 (complete gross resection) or optimal cytoreduction (<1 cm residual disease). Survival is strongly correlated with residual disease; R0 is the goal. Procedures may include bowel resection, splenectomy, diaphragmatic stripping, and liver resection. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS): Preferred for poor performance…

First-Line Regimen Comparison

The three pivotal front-line maintenance trials — SOLO-1 (olaparib), PRIMA (niraparib), and PAOLA-1 (olaparib + bevacizumab) — plus the VELIA study of veliparib give-and-continue defined the modern first-line landscape for advanced ovarian cancer. The table below compares these PARP inhibitor maintenance regimens against each other and against the carboplatin/paclitaxel chemotherapy backbone on which they are all built. Because each trial enrolled a different biomarker population (BRCA-mutated vs. HRD-positive vs. all-comers), the headline median PFS values are not directly cross-comparable…

Recurrent Disease Treatment

Ovarian cancer recurs in ~70–80% of patients with advanced-stage disease. The most important classification at relapse is platinum sensitivity, defined by the treatment-free interval (TFI) from the last platinum dose: • Platinum-sensitive: TFI ≥6 months — re-challenge with platinum-based doublet is indicated. Adding bevacizumab to the doublet (OCEANS, GOG213) significantly prolongs PFS. PARP inhibitor maintenance after a response to platinum re-challenge is standard for eligible patients (BRCA-mutated or HRD-positive). • Platinum-resistant: TFI <6 months — platinum re-challenge is unlikely…

PARP Inhibitor Re-Maintenance After Platinum Re-Challenge

For patients with platinum-sensitive recurrent ovarian cancer who respond (complete or partial) to a platinum-based re-challenge, PARP inhibitor maintenance prolongs the second remission — provided the patient is PARP-inhibitor-naïve (or, in select cases, had a long interval since prior PARP exposure). Three agents are approved in this setting, each supported by a dedicated randomized maintenance trial: olaparib (SOLO-2), niraparib (NOVA), and rucaparib (ARIEL3). Biomarker requirement is the key differentiator. Olaparib re-maintenance (SOLO-2) is restricted to BRCA1/2-mutated tumors, where…