Ovarian cancer

Overview

•6th most common cancer in women in the UK; ~7,500 new cases/year

•Most common cause of gynaecological cancer death in the UK (~4,100 deaths/year)

•~75% diagnosed at Stage III or IV - primary driver of poor outcomes

•5-year survival: Stage I ~90%, Stage III ~30%, Stage IV <15%

Classification

Ovarian tumour subtypes
FeatureEpithelialGerm cellSex-cord stromal
Proportion of malignant tumours~90%Minority; younger womenRare
Key subtypesHigh-grade serous (most common/lethal), mucinous, endometrioid, clear cellDysgerminoma, yolk sac tumour, teratoma, choriocarcinomaGranulosa cell (oestrogen), Sertoli-Leydig (androgens)
Tumour markersCA125AFP, beta-hCG (mandatory <40 years)Inhibin A and B
PrognosisVariable; HGSC worst overall; BRCA-mutated more platinum-sensitiveExcellent - dysgerminoma >90% cure even at advanced stageVariable

Feature	Epithelial	Germ cell	Sex-cord stromal
Proportion of malignant tumours	~90%	Minority; younger women	Rare
Key subtypes	High-grade serous (most common/lethal), mucinous, endometrioid, clear cell	Dysgerminoma, yolk sac tumour, teratoma, choriocarcinoma	Granulosa cell (oestrogen), Sertoli-Leydig (androgens)
Tumour markers	CA125	AFP, beta-hCG (mandatory <40 years)	Inhibin A and B
Prognosis	Variable; HGSC worst overall; BRCA-mutated more platinum-sensitive	Excellent - dysgerminoma >90% cure even at advanced stage	Variable

Presentation

•Persistent abdominal bloating - not cyclical

•Pelvic or abdominal pain

•Early satiety - due to ascites or mass effect

•Urinary urgency/frequency - bladder compression

•Postmenopausal bleeding - more typical of granulosa cell tumours (oestrogen excess)

•Ascites, shifting dullness - late sign of advanced disease

•Virilisation (hirsutism, voice deepening) - suggests Sertoli-Leydig cell tumour

🎯
NICE NG12 (2WW referral): refer if CA125 ≥35 IU/mL OR pelvic mass suspicious on ultrasound. Consider CA125 in women ≥50 with persistent bloating, early satiety, abdominal/pelvic pain, or urinary symptoms - especially >12 times/month.

Investigations

🥇 First-line

•CA125 - elevated (≥35 IU/mL) in ~80% of epithelial cancers; false positives include endometriosis, fibroids, PID

•Pelvic/abdominal ultrasound (transvaginal preferred) - assesses loculations, solid components, bilaterality, ascites

•First-line (women <40): AFP and beta-hCG - mandatory to exclude germ cell tumours

•First-line (suspected granulosa cell): Inhibin A and B

🥈 Second-line

•CT chest, abdomen, pelvis - staging investigation of choice; identifies peritoneal deposits, omental cake, lymphadenopathy, pleural effusion

🏆 Gold standard

•Histological analysis of surgical specimen or image-guided biopsy - definitive diagnosis, subtype, guides BRCA testing

🎯
Risk of Malignancy Index (RMI) = Ultrasound score (U) x Menopausal score (M) x CA125. Ultrasound score: 0 = no features, 1 = one feature, 3 = two or more features (multilocular cyst, solid areas, bilaterality, ascites, intra-abdominal metastases). Menopausal score: 1 = premenopausal, 3 = postmenopausal. RMI >250 (NICE) or >200 (SIGN) triggers referral to gynaecological oncology MDT.

Management

•Led by specialist gynaecological oncology MDT; depends on stage, histological subtype, performance status, and BRCA status

•Two pillars: cytoreductive (debulking) surgery + platinum-based combination chemotherapy

•Goal of surgery is complete macroscopic resection (R0) - residual disease volume is a key independent predictor of survival

•Standard chemotherapy: carboplatin + paclitaxel

•BRCA1/2-mutated HGSC: maintenance olaparib (PARP inhibitor) after platinum-based chemotherapy

Complications

Key complications
Ascites - requires paracentesis
Bowel obstruction - peritoneal deposits/adhesions
Pleural effusion - may need thoracocentesis
VTE - one of highest-risk malignancies
Surgical menopause - HRT counselling needed
Paclitaxel - peripheral neuropathy
Carboplatin - nephrotoxicity, myelosuppression
Platinum resistance - develops in ~70% of advanced cases

Prognosis

•Overall 5-year survival ~46% in England - reflects late-stage diagnoses

•BRCA-mutated HGSC has relatively better prognosis - more sensitive to platinum chemotherapy and benefits from PARP inhibitor maintenance

•Dysgerminoma (germ cell): >90% cure rate even at advanced stage due to high chemosensitivity

Risk Factors and Protective Factors

💡
Protective factors work by reducing lifetime ovulatory cycles - the incessant ovulation theory. OCP, multiparity, and breastfeeding all reduce cumulative DNA replication errors in the ovarian epithelium.

Prevention and Screening

•No population-based screening programme in the UK - UKCTOCS trial showed multimodal screening did not significantly reduce mortality

•BRCA1/BRCA2 testing: offered to women with qualifying family history and to all women with HGSC

•Risk-reducing bilateral salpingo-oophorectomy (RRBSO): BRCA1 carriers ~age 35-40; BRCA2 carriers ~age 40-45; reduces ovarian cancer risk by >95%