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"ovarian cancer"[MeSH Terms] AND ("treatment" OR "management")
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Carcinoma of the Ovary
Epidemiology
Ovarian cancer is the sixth most common malignancy in women and carries one of the highest mortalities among gynecologic cancers - overall 5-year survival is less than 50% because approximately two-thirds of women present with advanced disease. In 2024, ~19,710 new cases and >13,270 deaths were estimated in the USA alone. Peak incidence is in the 65-69 year age group for sporadic tumors, though the range spans the third to ninth decades.
- Risk factors: Nulliparity, obesity, infertility treatments, talc exposure, hormone replacement therapy, family history (BRCA mutations), Lynch syndrome
- Protective factors: Oral contraceptive use, multiparity, tubal ligation, breastfeeding, aspirin use
Classification (WHO)
1. Surface Epithelial-Stromal Tumors (~90% of malignancies)
Each type has benign, borderline (low malignant potential), and malignant variants:
| Type | Frequency |
|---|---|
| Serous (low-grade and high-grade adenocarcinoma) | 60-70% |
| Mucinous adenocarcinoma | 10-20% |
| Endometrioid adenocarcinoma | 10-15% |
| Clear cell adenocarcinoma | 10-15% |
| Brenner tumor (malignant) | Rare |
| Carcinosarcoma / Adenosarcoma | Rare |
2. Sex Cord-Stromal Tumors
Granulosa cell tumors, thecomas, fibrothecomas, Sertoli-Leydig cell tumors, steroid (lipid) cell tumors. May produce estrogen or androgens.
3. Germ Cell Tumors
Dysgerminoma (most common malignant germ cell tumor), yolk sac tumor, immature teratoma, mixed germ cell tumors. More common in younger women.
4. Metastatic (Krukenberg tumor)
Bilateral ovarian metastases from mucin-secreting GI primaries (gastric, colonic, pancreaticobiliary, breast).
- Robbins Pathologic Basis of Disease (WHO Table 22.3); Harrison's Principles of Internal Medicine 22E; Grainger & Allison Diagnostic Radiology
Molecular Pathogenesis: Type 1 vs Type 2
Type 1 (low-grade, indolent): Includes low malignant potential tumors, low-grade endometrioid/mucinous, and clear cell. Driven by mutations in KRAS, BRAF, PTEN, PIK3CA.
Type 2 (high-grade, aggressive): High-grade serous carcinoma. Serial genetic changes begin in the fallopian tube epithelium - loss of BRCA1/2 function + TP53 mutation (present in ~95%) leads to intraepithelial cancer, then peritoneal seeding. Additional mutations in NF1, RB1, CDK12 contribute.
- Harrison's Principles of Internal Medicine 22E
Genetics
- BRCA1 (chr 17q12-21): 39% lifetime risk of ovarian cancer up to age 70
- BRCA2 (chr 13q12-13): 11-17% lifetime risk up to age 70
- Lynch syndrome (mismatch repair gene mutations): 9-12% increased lifetime risk (also raises endometrial cancer risk)
- BRCA-associated cancers show increased sensitivity to platinum chemotherapy and PARP inhibitors
- Bailey & Love's Short Practice of Surgery 28E; Emery's Medical Genetics
Clinical Features
Symptoms (often vague and late-presenting):
- Abdominal distension/pain
- Change in appetite, early satiety, bloating
- Weight gain and increased girth (from ascites)
- Urinary obstruction
- Shortness of breath (pleural effusion)
- Gastrointestinal disturbance / change in bowel habit
Over 50% of women initially present to a speciality other than gynaecology.
Important differential: A pelvic mass + ascites usually indicates ovarian cancer but can also be Meigs' syndrome (benign fibroma + ascites + pleural effusion).
- Bailey & Love's 28E
Investigations
Tumour Markers
| Marker | Comments |
|---|---|
| CA-125 | Glycoprotein from coelomic/Müllerian epithelium; normal <35 U/mL. Elevated in 50% of stage I, >90% of advanced disease. Non-specific (also raised in pancreatitis, endometriosis, PID, menstruation, liver disease) |
| βHCG, LDH, αFP | Especially for germ cell tumors in women <40 years |
| CEA, CA 19-9 | For mucinous tumours; also evaluate for a GI primary |
| Inhibin | For sex cord-stromal tumors (granulosa cell) |
Risk of Malignancy Index (RMI)
RMI = U × M × CA-125
- U = ultrasound features (1 point each for multilocular cyst, solid components, metastases, ascites, bilateral lesions)
- M = menopausal status (1 = premenopausal; 3 = postmenopausal)
- CA-125 = level in U/mL
RMI helps triage patients to gynecological oncology.
Imaging
- Ultrasound (TVUS): First-line investigation
- CT chest/abdomen/pelvis: Staging prior to surgery; best preoperative tool for ovarian carcinoma
- MRI: Alternative for staging and characterizing pelvic mass
Screening
No national screening programme exists because no test reliably detects ovarian cancer at an early, curable stage. The UK Collaborative Trial of Ovarian Cancer Screening found combined CA-125 + TVUS had higher specificity than TVUS alone, but screening has not been shown to reduce mortality.
- Bailey & Love's 28E; Grainger & Allison's Diagnostic Radiology
FIGO Staging
| Stage | Description |
|---|---|
| I | Growth limited to the ovaries |
| II | Involvement of one or both ovaries with pelvic extension (uterus, bladder, sigmoid/rectum) or primary peritoneal cancer; no retroperitoneal nodes |
| III | Peritoneal implants outside the pelvis and/or retroperitoneal (pelvic/para-aortic) lymph node involvement |
| IV | Distant metastases (e.g., liver parenchyma, pleural effusion with cytology positive, inguinal nodes) |
Survival for properly staged IA/IB disease: 90-100% at 5 years. Overall (all stages): <50%.
- Bailey & Love's 28E; Berek & Novak's Gynecology; Washington Manual of Medical Therapeutics
Surgical Staging and Treatment
Cytoreductive Surgery (Primary Debulking)
The standard operation is TAH + BSO (total abdominal hysterectomy + bilateral salpingo-oophorectomy) via midline incision, with comprehensive staging:
- Free fluid / peritoneal washings from 4 quadrants
- Systematic exploration of all peritoneal surfaces (clockwise: cecum → ascending colon → right hemidiaphragm → transverse colon → left hemidiaphragm → descending colon)
- Supracolic omentectomy
- Pelvic and para-aortic lymphadenectomy
- Biopsies of all suspicious areas + random peritoneal biopsies (right hemi-diaphragm undersurface, bladder reflection, cul-de-sac, paracolic recesses, pelvic side walls)
- Appendicectomy for mucinous tumors
Exception: Young women with Stage I disease or borderline tumors who wish to preserve fertility may undergo unilateral oophorectomy (with caution; autologous ovarian tissue transplantation is contraindicated due to risk of seeding).
Neoadjuvant chemotherapy (NACT) + interval CRS: Used in advanced/frail patients where upfront primary debulking is not feasible. Has potential to downstage disease.
HIPEC (Hyperthermic Intraperitoneal Chemotherapy): Considered in Stage III epithelial disease at the time of interval CRS. An RCT by Van Driel et al. showed median overall survival of 45.7 vs 33.9 months with CRS+HIPEC vs CRS alone.
- Current Surgical Therapy 14E; Berek & Novak's Gynecology
Chemotherapy
- First-line (standard): Carboplatin + Paclitaxel (IV, 6 cycles) - well established from multiple RCTs
- Advanced disease adjunct: Bevacizumab (anti-VEGF) added to carboplatin+paclitaxel as first-line for advanced disease
- BRCA-mutated / HR-deficient disease: PARP inhibitors - Olaparib is FDA-approved for:
- Maintenance after platinum-sensitive recurrent disease
- BRCA-mutated recurrent ovarian cancer after ≥3 prior lines of chemotherapy (expanded indications 2020)
- Also approved: niraparib, rucaparib for similar indications
- Recurrent disease: Platinum-based re-treatment if platinum-sensitive (treatment-free interval >6 months); gemcitabine+carboplatin, topotecan, liposomal doxorubicin for platinum-resistant disease
- Goodman & Gilman's Pharmacology; Katzung's Basic & Clinical Pharmacology 16E; Berek & Novak's Gynecology
Spread and Prognosis
Routes of spread:
- Transcoelomic (most common): exfoliated cells spread along peritoneal fluid pathways to omentum, paracolic gutters, right hemidiaphragm, bowel surfaces
- Lymphatic: pelvic and para-aortic nodes
- Hematogenous: liver parenchyma, lungs (less common; pleural effusion more common)
Prognostic factors: FIGO stage, residual disease after cytoreduction (complete cytoreduction = best outcome), BRCA status, tumor grade, histologic subtype, performance status, ascites.
Key High-Yield Points
| Feature | Detail |
|---|---|
| Most common type | High-grade serous carcinoma |
| Tumor marker | CA-125 (>35 U/mL abnormal) |
| Spread pattern | Transcoelomic (peritoneal seeding) |
| BRCA1 lifetime risk | 39% |
| First-line chemo | Carboplatin + Paclitaxel |
| Targeted therapy | PARP inhibitors (olaparib, niraparib) for BRCA-mutated |
| Prophylactic surgery | Bilateral salpingo-oophorectomy for high-risk (BRCA+) |
| Fertility sparing | Only Stage I / borderline, unilateral oophorectomy |
| No national screening | No reliable early-stage test identified |
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