Ovarian Cancer
Ovarian cancer is the most lethal gynaecological malignancy, predominantly high-grade serous carcinoma, treated with debulking surgery and platinum-based chemotherapy, with PARP inhibitors for BRCA-mutated disease.
Key Facts
Most lethal gynaecological cancer in the UK; 75% diagnosed at Stage III-IV due to non-specific symptoms High-grade serous carcinoma (HGSC) is the most common subtype (70%); arises from fallopian tube fimbria NICE NG12: suspect ovarian cancer with persistent bloating, early satiety, pelvic pain, urinary frequency (≥12 times/month, new onset) CA-125 ≥35 IU/mL + pelvic USS → RMI calculation → if >250 refer to specialist centre Treatment: primary debulking surgery (aim for zero residual disease) + carboplatin AUC5 + paclitaxel 175mg/m² every 3 weeks × 6 cycles BRCA1/2 mutations: 10-15% of cases; offer olaparib maintenance (SOLO-1: 70% reduction in progression risk) Bevacizumab: anti-VEGF; added to chemotherapy and as maintenance in high-risk (ICON7 trial) 5-year survival: 45% overall; Stage I: 90%; Stage III: 25-30%
Overview
Key Facts
This entry covers ovarian cancer from the oncology perspective, focusing on systemic treatment principles. Ovarian cancer remains the most lethal gynaecological malignancy, largely because it presents at advanced stage. BRCA testing and PARP inhibitors have significantly altered the treatment landscape.
Epidemiology
- UK incidence: approximately 7,500 new cases per year
- Mortality: approximately 4,100 deaths per year
- Peak incidence: 60-64 years
- Lifetime risk: 1.8% overall; 40-60% with BRCA1; 10-30% with BRCA2
Aetiology
- As per gynaecological ovarian cancer entry: sporadic (85-90%), hereditary (10-15%)
- BRCA1, BRCA2, Lynch syndrome
- Protective: COC use, multiparity, breastfeeding, tubal ligation
Pathophysiology
- HGSC arises from serous tubal intraepithelial carcinoma (STIC) in the fallopian tube fimbriae
- Universal TP53 mutations; 50% have homologous recombination deficiency (HRD)
- Transcoelomic spread: peritoneal deposits, omental cake
- BRCA-deficient tumours: impaired DNA repair → sensitivity to platinum and PARP inhibitors (synthetic lethality)
Clinical Presentation
Symptoms
- Persistent bloating, early satiety, pelvic/abdominal pain, urinary urgency/frequency
- Ascites, palpable mass, pleural effusion
- Weight loss, fatigue
- Change in bowel habit
Red Flags
- Persistent symptoms ≥12 times/month, new onset, in women ≥50
- Ascites with pelvic mass
- CA-125 ≥35 IU/mL
- Family history of BRCA-associated cancers
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Benign ovarian cyst | Premenopausal, simple cyst, normal CA-125 | USS, RMI |
| Colorectal cancer | Altered bowel habit, rectal bleeding | Colonoscopy |
| Peritoneal carcinomatosis (other primary) | Ascites, GI symptoms | CT, cytology |
| Gastric cancer | Dyspepsia, weight loss | OGD |
Diagnosis / Investigation
Bedside
- Abdominal examination: ascites, palpable mass
- Pelvic examination
Bloods
- CA-125, HE4, FBC, U&Es, LFTs, albumin
- CEA, CA19-9 (if GI primary suspected)
- AFP, βhCG, LDH (young women: germ cell tumours)
Imaging
- Pelvic USS, CT CAP, PET-CT for staging
- MRI for indeterminate lesions
Special Tests
- RMI calculation
- Tissue biopsy (CT-guided or ascitic cytology)
- BRCA1/2 and HRD testing on tumour
- MMR/MSI testing
Management
Non-pharmacological
- MDT discussion at specialist gynaecological oncology centre
- Genetic counselling for BRCA carriers and families
- Nutritional and psychological support
Pharmacological
- First-line: carboplatin AUC5 + paclitaxel 175mg/m² q3w × 6 cycles
- Bevacizumab 15mg/kg q3w: added for Stage IIIB-IV; continued as maintenance
- PARP inhibitor maintenance:
- Olaparib 300mg BD: for BRCA-mutated (SOLO-1: 70% risk reduction)
- Niraparib 200-300mg OD: for all comers after platinum response (PRIMA)
- Neoadjuvant chemotherapy: 3 cycles → interval debulking surgery → 3 further cycles (CHORUS trial: non-inferior)
- Platinum-sensitive relapse (>6 months): rechallenge with platinum doublet ± bevacizumab; PARP maintenance
- Platinum-resistant relapse (<6 months): pegylated liposomal doxorubicin, weekly paclitaxel, topotecan, gemcitabine
Surgical/Interventional
- Primary debulking surgery: total hysterectomy + BSO + omentectomy + appendicectomy + peritoneal biopsies + lymphadenectomy; aim complete cytoreduction
- Interval debulking: after NACT if primary surgery not feasible
- Fertility-sparing surgery: unilateral salpingo-oophorectomy for Stage IA, Grade 1 in young women
- Risk-reducing BSO: for BRCA1 (by age 35-40) and BRCA2 (by age 40-45)
Referral Criteria
- RMI >250: urgent specialist referral
- Confirmed ovarian cancer: specialist gynaecological oncology centre
- All patients: BRCA testing
- BRCA carriers: genetics referral for family cascade testing
Prognosis
- Overall 5-year survival: 45%
- Stage I: 90%; Stage II: 60-70%; Stage III: 25-30%; Stage IV: 10-15%
- Complete cytoreduction: strongest surgical prognostic factor
- BRCA-mutated: paradoxically better prognosis (platinum and PARP sensitivity)
- PARP inhibitor era: significantly prolonged PFS and emerging OS benefits
- Most patients with advanced disease relapse within 18-24 months
- CA-125 monitoring: rising levels may indicate relapse (but early treatment of asymptomatic relapse does not improve OS per MRC OV05/EORTC 55955)
Other Relevant Information
Key Ovarian Cancer Trials
| Trial | Finding |
|---|---|
| ICON7 | Bevacizumab improved PFS in high-risk subgroup |
| SOLO-1 | Olaparib maintenance in BRCA+: 70% risk reduction |
| PRIMA | Niraparib maintenance all-comers: improved PFS |
| CHORUS | NACT non-inferior to primary debulking |
| PAOLA-1 | Olaparib + bevacizumab maintenance: PFS benefit in HRD+ |
| KEYNOTE-826 | Pembrolizumab for cervical (not ovarian, but similar ICI trials emerging) |
FIGO Staging Summary
| Stage | Description | 5-Year Survival |
|---|---|---|
| I | Confined to ovaries | 90% |
| II | Pelvic extension | 60-70% |
| III | Peritoneal deposits and/or lymph nodes | 25-30% |
| IV | Distant metastases (liver parenchyma, extra-abdominal) | 10-15% |