Ovarian cancer is the fifth most common cause of cancer death in women and the most lethal gynecologic malignancy. Approximately 19,700 new cases are diagnosed annually in the United States. Because ovarian cancer often presents with vague, nonspecific symptoms, roughly 60% of cases are diagnosed at an advanced stage (Stage III or IV), which significantly affects prognosis.
However, treatment advances — particularly the introduction of PARP inhibitors and refined surgical techniques — have meaningfully improved outcomes for many patients, especially those with BRCA-mutated tumors.
Types of Ovarian Cancer
Epithelial Ovarian Cancer
Epithelial tumors account for approximately 90% of all ovarian cancers. They arise from the surface epithelium of the ovary or, as now widely accepted, from the fallopian tube epithelium. Key subtypes include:
- High-grade serous carcinoma (HGSC) — The most common and aggressive subtype, representing 70% of epithelial ovarian cancers. Strongly associated with TP53 mutations and BRCA1/2 dysfunction. Most arise from the fimbriated end of the fallopian tube.
- Low-grade serous carcinoma — A less common, slower-growing subtype with different molecular characteristics (KRAS/BRAF mutations). Less responsive to chemotherapy but has a more indolent course.
- Endometrioid carcinoma — Accounts for approximately 10% of cases. Often associated with endometriosis and may present at an earlier stage.
- Clear cell carcinoma — Represents 5–10% of cases. Also linked to endometriosis. Known for relative chemoresistance and poorer response to standard platinum-based therapy.
- Mucinous carcinoma — A rare subtype (3–4% of cases) that may be difficult to distinguish from metastatic gastrointestinal cancers.
Germ Cell Tumors
Ovarian germ cell tumors arise from the egg-producing cells of the ovary and account for approximately 5% of ovarian cancers. They typically occur in younger women (teens to 30s). Subtypes include dysgerminoma, immature teratoma, endodermal sinus tumor (yolk sac tumor), and mixed germ cell tumors. These cancers are generally highly sensitive to platinum-based chemotherapy, with cure rates exceeding 90% even for advanced-stage disease.
Sex Cord-Stromal Tumors
Stromal tumors account for approximately 5% of ovarian cancers and arise from the connective tissue cells that produce hormones. The most common subtypes are granulosa cell tumors and Sertoli-Leydig cell tumors. These tumors may produce excess estrogen or androgens, causing symptoms such as abnormal uterine bleeding or virilization. They tend to be diagnosed at an earlier stage and carry a more favorable prognosis, though late recurrences can occur years after initial treatment.
Diagnosis and CA-125
The diagnostic workup for suspected ovarian cancer typically includes:
- Pelvic examination — May reveal an adnexal mass or ascites.
- Transvaginal ultrasound — First-line imaging to evaluate ovarian masses. Complex masses with solid components, irregular borders, or internal blood flow raise suspicion for malignancy.
- CA-125 blood test — A tumor marker elevated in approximately 80% of advanced epithelial ovarian cancers. Normal values are below 35 U/mL. However, CA-125 can be elevated in many benign conditions (endometriosis, pelvic inflammatory disease, liver disease) and is not elevated in all ovarian cancer subtypes.
- CT scan of chest, abdomen, and pelvis — Used to evaluate the extent of disease and plan for surgery.
- HE4 (Human epididymis protein 4) — A newer marker that, combined with CA-125 in the ROMA (Risk of Ovarian Malignancy Algorithm) score, improves diagnostic accuracy.
Staging
Ovarian cancer is surgically staged using the FIGO (International Federation of Gynecology and Obstetrics) system:
| Stage | Description | 5-Year Survival |
|---|---|---|
| Stage I | Confined to one or both ovaries | ~90% |
| Stage II | Pelvic extension (uterus, fallopian tubes, other pelvic tissues) | ~70% |
| Stage III | Spread to the peritoneum outside the pelvis and/or retroperitoneal lymph nodes | ~39% |
| Stage IV | Distant metastases (liver parenchyma, extra-abdominal sites, pleural effusion with positive cytology) | ~17% |
Surgical Treatment: Debulking Surgery
Surgery is the cornerstone of ovarian cancer treatment and serves both diagnostic (staging) and therapeutic purposes. The primary goal of surgery in advanced ovarian cancer is optimal cytoreduction (debulking), defined as removing all visible tumor or reducing residual disease to less than 1 cm. Complete gross resection (no visible residual disease) is associated with the best outcomes.
A standard surgical procedure for ovarian cancer typically includes:
- Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO)
- Omentectomy (removal of the omentum, a common site of metastasis)
- Pelvic and para-aortic lymph node dissection
- Peritoneal biopsies and washings
- Appendectomy (particularly for mucinous tumors)
- Resection of any other involved structures (bowel, diaphragm, spleen) as needed to achieve optimal debulking
For young women with early-stage disease (Stage IA, Grade 1) who wish to preserve fertility, unilateral salpingo-oophorectomy with comprehensive staging may be appropriate.
Neoadjuvant Chemotherapy
When primary surgery is not feasible due to extensive disease burden or patient fitness, neoadjuvant chemotherapy (NACT) with 3–4 cycles of platinum-based therapy followed by interval debulking surgery (IDS) is an established alternative. The CHORUS and EORTC 55971 trials demonstrated that NACT followed by IDS was non-inferior to primary debulking surgery in terms of overall survival, with lower surgical morbidity.
Chemotherapy
First-Line: Platinum-Based Chemotherapy
The standard first-line chemotherapy regimen for epithelial ovarian cancer is the combination of carboplatin (AUC 5–6) plus paclitaxel (175 mg/m²), given intravenously every 3 weeks for 6 cycles. This combination achieves initial response rates of 70–80% in advanced disease.
Alternative approaches include:
- Dose-dense weekly paclitaxel — Paclitaxel given weekly instead of every 3 weeks, combined with every-3-week carboplatin. The Japanese JGOG 3016 trial showed improved PFS and OS with this schedule, though Western trials have shown less consistent benefit.
- Intraperitoneal (IP) chemotherapy — Delivery of cisplatin and paclitaxel directly into the peritoneal cavity. GOG 172 showed a significant survival advantage, though adoption has been limited by toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of interval debulking surgery is an active area of research.
- Bevacizumab (Avastin) — An anti-VEGF antibody added to carboplatin/paclitaxel and continued as maintenance. The GOG 218 and ICON7 trials demonstrated improved PFS, particularly in patients with suboptimal debulking or Stage IV disease.
PARP Inhibitors and Maintenance Therapy
PARP (poly ADP-ribose polymerase) inhibitors represent one of the most significant advances in ovarian cancer treatment. These drugs block a DNA repair pathway that cancer cells — particularly those with BRCA mutations or homologous recombination deficiency (HRD) — rely on for survival.
Olaparib (Lynparza)
The first PARP inhibitor approved for ovarian cancer. Key trial results include:
- SOLO-1 trial — First-line maintenance olaparib in BRCA-mutated advanced ovarian cancer showed median PFS of 56 months versus 13.8 months with placebo. At 7 years, 67% of patients in the olaparib arm had not experienced progression or death.
- SOLO-2 trial — Maintenance olaparib in relapsed BRCA-mutated ovarian cancer improved PFS from 5.5 to 19.1 months.
Niraparib (Zejula)
Approved for maintenance therapy regardless of BRCA or HRD status. The PRIMA/ENGOT-OV26 trial demonstrated PFS benefit with niraparib maintenance after first-line platinum-based chemotherapy, including in patients without BRCA mutations or HRD.
Rucaparib (Rubraca)
Approved for maintenance treatment of recurrent ovarian cancer that responded to platinum-based chemotherapy. The ARIEL3 trial showed improved PFS across all biomarker subgroups.
Recurrent Ovarian Cancer
Despite high initial response rates, approximately 70–80% of patients with advanced ovarian cancer will experience recurrence. Treatment of recurrent disease depends on the platinum-free interval (PFI):
- Platinum-sensitive relapse (PFI ≥6 months) — Retreatment with platinum-based combination chemotherapy (carboplatin plus paclitaxel, gemcitabine, or pegylated liposomal doxorubicin) followed by maintenance PARP inhibitor therapy.
- Platinum-resistant relapse (PFI <6 months) — Single-agent non-platinum chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin, topotecan, gemcitabine) with or without bevacizumab. Response rates are lower (10–25%).
Genetic Testing and Prevention
All women diagnosed with epithelial ovarian cancer should undergo germline and somatic BRCA1/2 testing. Results guide treatment decisions (PARP inhibitor eligibility) and have implications for family members. Additional genes tested in multigene panels include RAD51C, RAD51D, BRIP1, and mismatch repair genes (Lynch syndrome).
Risk-reducing strategies for high-risk women include:
- Risk-reducing bilateral salpingo-oophorectomy (RRBSO) — Recommended for BRCA1 carriers by age 35–40 and BRCA2 carriers by age 40–45. Reduces ovarian cancer risk by approximately 80%.
- Oral contraceptive use — Associated with a 40–50% reduction in ovarian cancer risk with 5 or more years of use, even in BRCA carriers.
- Opportunistic salpingectomy — Removal of the fallopian tubes during other gynecologic surgeries in average-risk women, based on evidence that many high-grade serous cancers originate in the fallopian tube.