Ovarian cancer

Introduction
Ovarian cancer is a malignant neoplasm arising from different cell types within the ovary. It is the most lethal of the gynecologic cancers due to its typically late presentation, as early-stage disease often produces few or no symptoms. The majority of cases are epithelial ovarian carcinomas, though germ cell and sex cord–stromal tumors are also important subtypes.

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Epidemiology

• Incidence: Accounts for ~3% of cancers in women but is the leading cause of death from gynecologic malignancy.

• Age: Peak incidence in women aged 55–65 years.

• Risk factors:

  • Increasing age.

  • Family history (especially BRCA1/BRCA2 mutations, Lynch syndrome).

  • Early menarche, late menopause.

  • Nulliparity or infertility.

• Protective factors:

  • Oral contraceptive use.

  • Multiple pregnancies.

  • Breastfeeding.

  • Tubal ligation or salpingo-oophorectomy.

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Types and Pathology

1. Epithelial tumors (90% of cases):

• High-grade serous carcinoma (most common and most aggressive).

• Endometrioid carcinoma.

• Mucinous carcinoma.

• Clear cell carcinoma.

• Low-grade serous carcinoma.

2. Germ cell tumors:

• Dysgerminoma.

• Yolk sac tumor.

• Immature teratoma.

3. Sex cord–stromal tumors:

• Granulosa cell tumor.

• Sertoli–Leydig cell tumor.

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Pathophysiology
Most high-grade serous carcinomas originate from the epithelium of the distal fallopian tube, then spread to the ovary and peritoneum. Ovarian cancer spreads by:

• Transcoelomic spread within the peritoneal cavity.

• Lymphatic spread to pelvic and para-aortic nodes.

• Hematogenous spread (less common, to liver, lung, bone).

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Clinical Features

Early stages are often asymptomatic.
Non-specific symptoms:

• Abdominal bloating or distension.

• Pelvic or abdominal pain.

• Early satiety, loss of appetite.

• Urinary urgency or frequency.

• Unexplained weight loss or gain.

Advanced disease:

• Ascites.

• Bowel obstruction.

• Pleural effusion.

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Physical Examination

• Abdominal distension.

• Palpable adnexal mass.

• Signs of ascites (fluid wave, shifting dullness).

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Investigations

Laboratory tests:

• Tumor markers:

  • CA-125: Elevated in ~80% of epithelial ovarian cancers (less sensitive in early disease, not specific).

  • HE4: May help differentiate benign from malignant masses.

  • AFP, β-hCG, LDH for suspected germ cell tumors.

• CBC, LFTs, renal function tests.

Imaging:

• Transvaginal ultrasound: First-line for adnexal mass evaluation; assess morphology, solid components, septations, papillary projections, vascularity.

• CT abdomen and pelvis: For staging and surgical planning.

• Chest imaging: Detect pleural effusion or lung metastases.

Definitive diagnosis:

• Histopathology from surgical specimen; biopsy rarely performed before surgery unless diagnosis uncertain or inoperable disease suspected.

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Staging
Based on FIGO system:

• Stage I: Confined to ovaries.

• Stage II: Pelvic extension.

• Stage III: Peritoneal metastases outside pelvis and/or positive retroperitoneal lymph nodes.

• Stage IV: Distant metastases (e.g., liver parenchyma, lung).

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Management

1. Surgery

• Mainstay for diagnosis, staging, and debulking (cytoreduction).

• Standard primary surgery:

  • Total abdominal hysterectomy.

  • Bilateral salpingo-oophorectomy.

  • Omentectomy.

  • Peritoneal washings, biopsies.

  • Pelvic and para-aortic lymphadenectomy in selected cases.

• Goal: Optimal cytoreduction (residual disease <1 cm).

2. Chemotherapy

• Indicated for most patients except some with Stage IA/IB low-grade tumors.

• Standard regimen for epithelial ovarian cancer:

  • Carboplatin (AUC 5–6 IV day 1) + Paclitaxel (175 mg/m² IV day 1) every 21 days × 6 cycles.

• Intraperitoneal chemotherapy in selected optimally debulked patients.

3. Neoadjuvant Chemotherapy

• Considered for advanced disease when primary cytoreductive surgery is not feasible; followed by interval debulking surgery.

4. Targeted Therapy

• PARP inhibitors (e.g., olaparib, niraparib, rucaparib): Maintenance therapy for BRCA-mutated or homologous recombination–deficient tumors.

• Bevacizumab: Anti-VEGF monoclonal antibody; can be combined with chemotherapy and continued as maintenance.

5. Treatment of Other Subtypes

• Germ cell tumors: Fertility-sparing surgery + chemotherapy (BEP: bleomycin, etoposide, cisplatin).

• Sex cord–stromal tumors: Surgery ± chemotherapy, hormonal therapy in some cases.

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Follow-up

• History, examination, and CA-125 monitoring every 3–6 months for 5 years.

• Imaging only if clinically indicated.

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Prognosis

• Five-year survival varies by stage:

  • Stage I: 70–90%

  • Stage III–IV: 20–40%

• Prognosis influenced by stage, residual disease after surgery, tumor grade, histological subtype, and BRCA mutation status.

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Prevention and Risk Reduction

• Genetic counseling and testing for women with strong family history or BRCA mutations.

• Risk-reducing salpingo-oophorectomy in high-risk women after completion of childbearing.

• Oral contraceptives reduce lifetime risk when used ≥5 years.