Key Facts

Ovarian cancer is the most lethal gynaecological malignancy, largely because the majority present at advanced stage. High-grade serous carcinoma is the most common subtype, and BRCA mutations are significant risk factors.

Epidemiology

• UK incidence: approximately 7,500 new cases per year (6th most common cancer in women)
• Mortality: approximately 4,100 deaths per year (highest of gynaecological cancers)
• Peak incidence: 60-64 years
• Lifetime risk: 1.8% (1 in 54 women); increased to 40-60% with BRCA1 mutation

Aetiology

• Sporadic: 85-90% of cases; risk increases with age, nulliparity, early menarche, late menopause
• Hereditary: 10-15% of cases; BRCA1 (40-60% lifetime risk), BRCA2 (10-30% lifetime risk), Lynch syndrome (10-12% risk)
• Protective factors: COC use (50% risk reduction with ≥5 years use), multiparity, breastfeeding, tubal ligation
• Incessant ovulation hypothesis: repeated ovulation causes epithelial damage and repair, increasing mutation risk

Pathophysiology

• High-grade serous carcinoma (HGSC): most common (70%); arises from fallopian tube fimbrial epithelium (serous tubal intraepithelial carcinoma, STIC); TP53 mutations universal
• Low-grade serous: indolent; KRAS/BRAF mutations
• Endometrioid and clear cell: arise from endometriosis; ARID1A mutations
• Mucinous: often GI origin; KRAS mutations
• Transcoelomic spread is the primary mode of dissemination (peritoneal deposits, omental cake)

Common Symptoms (Non-specific)

• Persistent abdominal bloating (>12 times/month)
• Feeling full quickly (early satiety) or loss of appetite
• Pelvic or abdominal pain
• Increased urinary urgency or frequency
• Change in bowel habit
• Unexplained weight loss or gain
• Fatigue

Examination Findings

• Ascites (shifting dullness)
• Palpable pelvic or abdominal mass
• Pleural effusion
• Sister Mary Joseph nodule (umbilical metastasis)

Red Flags

• Persistent symptoms for ≥3 weeks in women ≥50 years (or any age with family history)
• Palpable pelvic mass
• Ascites in a woman
• New IBS symptoms in a woman >50
• CA-125 ≥35 IU/mL

Bedside

• Abdominal examination: ascites, palpable mass
• Pelvic examination: fixed, solid, irregular adnexal mass

Bloods

• CA-125: first-line tumour marker (elevated >35 IU/mL in 80% of advanced epithelial ovarian cancer)
• HE4: second-line marker; combined with CA-125 in ROMA algorithm
• FBC, U&Es, LFTs, albumin (baseline and nutritional status)
• CEA, CA19-9 (if GI primary suspected)
• AFP, βhCG, LDH (if germ cell tumour suspected in young women)

Imaging

• Pelvic USS (TVS): first-line; assess ovarian morphology, solid components, Doppler flow
• CT chest/abdomen/pelvis: staging investigation (peritoneal deposits, lymphadenopathy, omental cake, liver metastases)
• MRI pelvis: for indeterminate USS findings
• PET-CT: for suspected recurrence

Special Tests

• RMI calculation: USS score × menopausal status × CA-125; >250 → specialist referral
• CT-guided biopsy or ascitic tap for cytology: if diagnosis uncertain or neoadjuvant chemotherapy planned
• Genetic testing: BRCA1/2 and Lynch syndrome testing for all non-mucinous epithelial ovarian cancers

Non-pharmacological

• MDT discussion in specialist gynaecological oncology centre
• Psychological support and specialist nurse input
• Nutritional support (ascites, cachexia)
• Genetic counselling for BRCA carriers and family members

Pharmacological

• First-line chemotherapy: carboplatin AUC 5-6 + paclitaxel 175mg/m² every 3 weeks for 6 cycles
• Bevacizumab: anti-VEGF; added to chemotherapy and as maintenance in advanced disease (ICON7 trial)
• PARP inhibitors: olaparib 300mg BD (SOLO-1 trial), niraparib (PRIMA trial); maintenance after platinum-sensitive response; greatest benefit in BRCA-mutated and HRD-positive tumours
• Neoadjuvant chemotherapy (NACT): 3 cycles pre-surgery + 3 cycles post-surgery for patients unsuitable for primary debulking (CHORUS trial)
• Second-line: platinum rechallenge if relapse >6 months; weekly paclitaxel, pegylated liposomal doxorubicin, or gemcitabine if platinum-resistant

Surgical/Interventional

• Primary debulking surgery: aim for complete cytoreduction (no residual disease)
  • Total abdominal hysterectomy + bilateral salpingo-oophorectomy
  • Omentectomy, peritoneal biopsies, appendicectomy (mucinous)
  • Pelvic and para-aortic lymphadenectomy
  • Bowel resection if involved
• Interval debulking surgery: after NACT if not suitable for primary surgery
• Fertility-sparing surgery: unilateral salpingo-oophorectomy + staging for Stage IA in young women
• Risk-reducing surgery: bilateral salpingo-oophorectomy for BRCA carriers (recommended by age 35-40 for BRCA1, 40-45 for BRCA2)

Referral Criteria

• RMI >250 or suspicious imaging: urgent referral to gynaecological oncology
• All confirmed ovarian cancers: management in specialist centre
• BRCA carriers: genetics referral for risk-reducing surgery counselling
• Relapsed disease: specialist oncology review

• Overall 5-year survival: 45%
• Stage I: 90% 5-year survival
• Stage II: 60-70%
• Stage III: 25-30%
• Stage IV: 10-15%
• Complete cytoreduction (no residual disease) is the single most important prognostic factor at surgery
• BRCA-mutated tumours: paradoxically better prognosis due to platinum sensitivity
• PARP inhibitor maintenance (olaparib): 70% reduction in risk of progression in BRCA-mutated disease (SOLO-1)
• Recurrence is common in advanced disease; most patients relapse within 18-24 months

Ovarian Cancer Subtypes

Landmark Trials