Ovarian Cancer
Summary
Ovarian cancer is the deadliest gynaecological malignancy, primarily because >70% of cases are diagnosed at an advanced stage (Stage III/IV). It comprises three main types: Epithelial (90%, e.g., High-Grade Serous), Germ Cell (rare, young women), and Sex Cord-Stromal. Clinical presentation is often non-specific ("The Silent Killer"), mimicking IBS or urinary issues. Early recognition relies on identifying the "BEAT" symptoms (Bloating, Eating difficulty, Abdominal pain, Toilet habits). Diagnosis involves CA125 and Ultrasound to calculate a Risk of Malignancy Index (RMI). Treatment is primary surgical cytoreduction (debulking) combined with platinum-taxane chemotherapy. [1,2]
Key Facts
- Origins: Most "ovarian" high-grade serous carcinomas actually originate from the fimbriae of the Fallopian Tube (Serous Tubal Intraepithelial Carcinoma - STIC).
- The "IBS" Mimic: NICE guidelines state that any woman >50 presenting with NEW onset Irritable Bowel Syndrome (IBS) symptoms must have a CA125 checked. IBS rarely starts at 50.
- CA125 Utility: Sensitive but NOT specific. Raised in endometriosis, fibroids, menstruation, pregnancy, and heart failure.
- RMI Score: The gold standard for triage. RMI >200-250 usually warrants referral to a specialist Gynae-Oncology centre.
Clinical Pearls
BEAT Symptoms:
- B: Bloating (Persistent, doesn't come and go like gas).
- E: Eating less / feeling full quickly (Early satiety).
- A: Abdominal/Pelvic pain.
- T: Toilet changes (Urgency or bowel changes).
Sister Mary Joseph Nodule: A palpable nodule in the umbilicus. Represents metastatic spread via the falciform ligament. It is an ominous sign of advanced intra-abdominal malignancy (Ovarian/Gastric).
Meigs' Syndrome: Triad of Ovarian Fibroma (Benign) + Ascites + Pleural Effusion. Mimics cancer perfectly but is cured by removing the fibroma.
Incidence
- Peak Age: Post-menopausal (mean age 63).
- Lifetime Risk: 1 in 70-80.
Risk Factors
Generally related to "Incessant Ovulation" (more cycles = more risk).
- Genetic: BRCA1 (40-60% risk), BRCA2 (10-30% risk), Lynch Syndrome (HNPCC).
- Reproductive: Nulliparity, Early menarche, Late menopause, IVF?
- Hormonal: HRT (slight increase), Endometriosis (Clear cell/Endometrioid types).
Protective Factors
Anything that stops ovulation.
- Combined Oral Contraceptive Pill (Reduces risk by 50% after 5 years use).
- Pregnancy / Breastfeeding.
- Tubal Ligation / Salpingectomy.
Classification (WHO)
- Epithelial (90%):
- High-Grade Serous (70%): Aggressive. Tubal origin. TP53 mutations.
- Endometrioid: Associated with endometriosis/Lynch. Better prognosis.
- Clear Cell: Associated with endometriosis. Chemo-resistant.
- Mucinous: Can be huge (basketball size). Rule out GI primary (Krukenberg).
- Germ Cell (less than 5%):
- Teratoma (Dermoid cyst - benign or immature), Dysgerminoma. Young women. Tumour markers: AFP, hCG, LDH.
- Sex Cord-Stromal:
- Granulosa Cell Tumour (Secretes Estrogen -> PMB/Endometrial Ca). Sertoli-Leydig (Androgens -> Virilisation).
Spread
- Transcoelomic: Exfoliates cells into peritoneal fluid -> Omental cake, Ascites.
- Lymphatic: Para-aortic nodes.
Symptoms
Paraneoplastic Syndromes
- Abdomen: Distension (fluid thrill/shifting dullness). Palpable mass arising from pelvis. Palpable omental cake (epigastric).
- Pelvic (Bimanual / Speculum): Adnexal mass (solid, fixed, irregular, bilateral). Nodules in Pouch of Douglas.
- Chest: Pleural effusion (decreased breath sounds at bases).
- Nodes: Supraclavicular (Virchow's node).
Primary Care / Triage
- CA125: Blood test.
- If >35 U/ml -> Urgent Ultrasound.
- Transvaginal Ultrasound (TVUS):
- Assess: Multilocular? Solid areas? Bilateral? Ascites?
Risk of Malignancy Index (RMI)
RMI = U x M x CA125
- U (Ultrasound Score): 0, 1, or 3.
- Points for: Multilocular, Solid areas, Mets, Ascites, Bilateral.
- 0 features = U0. 1 feature = U1. 2-5 features = U3.
- M (Menopausal Status):
- Pre-menopause = 1.
- Post-menopause = 3.
- CA125: Absolute value.
- Example: Post-menopausal (3) x Complex Cyst (3) x CA125 (50) = 450. (High risk).
Staging (Secondary Care)
- CT Chest/Abdo/Pelvis: Staging.
- MRI Pelvis: To differentiate indeterminate masses.
- AFP / hCG: If less than 40 years old (Germ cell).
Management Algorithm
SUSPICIOUS PELVIC MASS
(High RMI / Ascites)
↓
CT STAGING
↓
┌─────────────┴─────────────┐
OPERABLE (Stage 1-3) INOPERABLE / FRAIL
↓ (Stage 4)
PRIMARY SURGERY ↓
(Debulking) BIOPSY (IR guided)
↓ ↓
ADJUVANT CHEMO NEOADJUVANT CHEMO
(Carbo/Taxol) (3 cycles)
↓
INTERVAL SURGERY?
1. Surgery (Cytoreduction)
The goal is Macroscopic Complete Resection (R0 - no visible disease left). Survival correlates directly with residual disease.
- Procedure: TAH + BSO + Omentectomy + Appendicectomy (mucinous) + Peritoneal strippings/Bowel resection if needed.
2. Chemotherapy
- Standard: Carboplatin and Paclitaxel (Taxol).
- Pattern: Every 3 weeks for 6 cycles.
- Intraperitoneal Chemo: HIPEC? (Hyperthermic Intraperitoneal Chemotherapy) - controversial but used in select centres.
3. Targeted Therapy
- Bevacizumab (Avastin): Anti-VEGF monoclonal antibody. Improves Progression Free Survival in advanced disease.
- PARP Inhibitors (Olaparib/Niraparib):
- For BRCA mutated (or Homologous Recombination Deficient - HRD) tumours.
- Why? Synthetic Lethality. Cancer cells can't repair DNA single-strand breaks (PARP blocked) OR double-strand breaks (BRCA broken) -> Cell death.
- Bowel Obstruction: Common terminal event ("Carcinomatosis peritonei"). Managed conservatively or usually palliative.
- Ascites: Requiring recurrent drainage/permanent drains.
- Chemo Toxicity: Neuropathy (Taxol), Nephrotoxicity, Neutropenia.
- Overall 5-year survival: ~45% (poor).
- Stage 1: >90%.
- Stage 3/4: less than 30%.
- Recurrence is very common (70%) within 3 years.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| NG61 | NICE (2011/20) | Measure CA125 in IBS >50y. Use RMI for referral. Carboplatin/Paclitaxel first line. |
| Ovarian Cancer | ESGO / ESMO | Surgery aimed at R0 resection. PARP inhibitors for maintenance. |
Landmark Studies
1. ICON Studies (e.g., ICON7)
- Intervention: Bevacizumab added to chemo.
- Result: Modest PFS benefit, especially in high-risk groups.
2. SOLO-1 Trial (2018)
- Intervention: Maintenance Olaparib in BRCA-mutated advanced ovarian cancer.
- Result: Huge benefit. 60% progression-free at 3 years vs 27% placebo.
- Impact: Established PARP inhibitors as standard of care.
3. UKCTOCS (Screening Trial)
- Question: Does screening (CA125/US) save lives?
- Result: Detected cancer earlier, but did NOT significantly reduce mortality.
- Impact: Population screening is currently NOT recommended.
Why was it found so late?
Ovarian cancer is sneaky. The ovaries float deep in the pelvis, so tumors can grow large without causing a lump you can feel. The symptoms (bloating, feeling full) happen to everyone occasionally, so alarm bells don't ring until it spreads.
What is Debulking?
The surgery is extensive because the cancer spreads like "sand" across the lining of the tummy. The surgeon has to remove the womb, ovaries, and the fatty apron (omentum) to scoop out as much "sand" as possible. The less left behind, the better the chemo works.
Why do I need gene testing?
We test for the BRCA gene (Angelina Jolie gene). If you have it:
- We have special drugs (PARP inhibitors) that kill this specific type of cancer.
- Your family might be at risk and can have preventative surgery.
Primary Sources
- NICE Guideline NG122. Ovarian cancer: recognition and initial management. 2011 (Updated 2024).
- Moore K, et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer (SOLO-1). N Engl J Med. 2018;379:2495-2505. PMID: 30345884.
- Jacobs IJ, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet. 2016;387:945-956. PMID: 26707054.
Common Exam Questions
- General Practice: "55yo female, new IBS symptoms. Action?"
- Answer: CA125.
- Gynaecology: "Formula for RMI?"
- Answer: U x M x CA125.
- Oncology: "Side effect of Paclitaxel?"
- Answer: Peripheral Neuropathy / Alopecia.
- Pathology: "Tumour marker for Dysgerminoma?"
- Answer: LDH / hCG. (Not CA125).
Viva Points
- Krukenberg Tumour: What is it? Metastasis to ovary from GI primary (usually Stomach - Signet Ring cells). Bilateral solid masses.
- Meigs' Syndrome: Benign ovarian fibroma + Ascites + Pleural effusion. Why is it important? It looks like Stage 4 cancer but is curable by simple excision.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.