Ovarian Cancer

1. Ovarian Cancer Tim Broadhead Consultant Gynaecologist & Gynaecological Oncologist

3. Ovarian Cancer • Introduction • Pathology • Aetiology • Staging • Symptoms & Examination • Tests • Treatment • Future Developments

4. Introduction • 6700 cases in UK each year • 5th commonest cancer in women • Lifetime risk 1 in 48 • Higher incidence in postmenopausal women

5. 4300 die each year Leading cause of death from gynae cancer Advanced disease at presentation Median PFS ~1 to 2 years Median OS ~ 2.5 years 5yr survival ~ 30% Introduction Poor prognosis & rarely cured 1090 patients Leeds Cancer Centre 1990-2005

6. Ovarian cancer subtypes Epithelial (90%) Serous Endometrioid Mucinous Clear cell Germ cell tumours (10%) Sex-cord stromal cell tumours (rare) Pathology • Primary peritoneal cancer

7. Aetiology Most cases sporadic • “Incessant Ovulation Theory” • Pregnancy / COCP protective • Diet • Animal fat / Galactose / Alcohol • Environmental factors • Talc exposure • Hysterectomy / Tubal Ligation

8. Aetiology Hereditary 5-10% Breast / Ovarian Cancer Syndrome • BRCA1 (up to 60% lifetime risk) • BRCA2 (up to 25% lifetime risk) • Tumour suppressor genes HNPCC syndrome • Mutations of mismatch repair genes

9. FIGO Staging • I – confined to ovary • II – confined to pelvis

10. FIGO Staging • III - abdominal extension or lymph nodes • IV - distant metastases

11. Importance of stage 5 year survival Stage 1 - 90% Stage 2 - 65% Stage 3 - 35% Stage 4 - 10% 20% 60% 20% Staging 1090 patients Leeds Cancer Centre 1990-2005

12. Symptoms • “Silent Killer” • 1 case every 5 years • 1 every 25,000 consultations

13. Symptoms “Ovarian cancer is not silent, rather its sound is going unheard”

14. Symptoms Earlier diagnosis and correct pathway sooner - improved survival?

15. Symptoms • Carry out tests if any of the following on a frequent basis – more than 12 times a month (esp if >50 years old) • Persistent abdo distension • Feeling full, loss of appetite or both • Pelvic or abdo pain • Increased urinary urgency, frequency or both

16. Symptoms • Carry out appropriate tests for ovarian cancer in any woman of 50 or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS) “ITS NOT IBS, ITS OVARIAN CANCER”

17. Symptoms • Consider tests if: • Unexplained weight loss • Fatigue • Changes in bowel habit • Advise any woman who is not suspected of having ovarian cancer to return to her GP if her symptoms become more frequent and/or persistent

18. Examination • Abdo / pelvic examination • Ascites • Abdo mass • Pelvic mass Refer the woman urgently if physical examination identifies ascites and/or a pelvic or abdominal mass (which is not obviously uterine fibroids) →

19. Which Tests ? • CA125 • tumour associated antigen • normal level <35 iu/ml •  85% epithelial ovarian cancer but also in benign conditions (fibroids, PID, endometriosis) •  in only 50% of stage 1 ovarian cancer

20. Which Tests? • If CA125 >35 arrange USS abdo / pelvis Benign Malignant

21. First tests in primary care Measure serumCA125 35 IU/ml or greater Less than 35 IU/ml Assess carefully: are other clinical causes of symptoms apparent? Ultrasound of abdomen and pelvis Normal Suggestive of ovarian cancer Yes No Refer urgently Investigate Advise to return to GP if symptoms become more frequent and/or persistent

23. Detection in primary care Women presents to GP Ascites and/or pelvic or abdominal mass GP assesses symptoms Support and information Tests in primary care Suspicion of ovarian cancer Urgent referral: assessment in secondary care

24. Establishing the diagnosis • CT scan Complex pelvic mass Omental cake Liver surface deposits

25. Establishing the diagnosis • Discuss in MDT • Suspected early stage disease → local cancer unit • Advanced disease → cancer centre

26. Treatment of Early Ovarian Cancer

27. Surgery • Suspected early stage disease Staging Laparotomy • TAH / BSO • Infracolic omentectomy • Pelvic / PA node sampling • Peritoneal washings • Biopsies of peritoneum Fertility sparing surgery Laparoscopic surgery

28. Surgery

29. Stage important in prognosis and treatment 5 year survival Stage 1 - 90% Stage 2 - 65% Stage 3 - 35% Stage 4 - 10% 20% 60% 20% Staging 1090 patients Leeds Cancer Centre 1990-2005

30. Treatment of Advanced Disease Surgery or Primary Chemotherapy?

31. Surgery for advanced disease • “Debulking surgery” • Complete debulking - aim to leave no macroscopic disease • Optimal debulking <1cm • Bowel resection / stoma / splenectomy / peritoneal stripping / pelvic & PA lymphadenectomy

32. Surgery for advanced disease • MDT review • Disease considered resectable • Medically fit • → debulking surgery

33. Surgery • Volume of residual disease directly determines survival • Optimal debulking • 39 months (median survival) • Sub-optimal debulking • 17 months (median survival) • Surgical skill or tumour biology?

34. “Inoperable disease”

35. Neoadjuvant Chemotherapy and Interval Debulking Surgery • Disease not resectable • Medically unfit • Scan guided core biopsy • 3 cycles chemo → IDS → 3 cycles chemo

36. Neoadjuvant Chemotherapy and Interval Debulking Surgery • Future standard of care? • Reduced morbidity and mortality • Results of CHORUS awaited

37. Chemotherapy Early stage disease

38. Early stage disease • Stage I & II Died Alive

39. Early stage disease • Stage I & II • AdjuvantChemotherapy - Increase chance of cure Died Cured by chemo Alive ICON1/Action: JNCI 2003

40. Early stage disease • Current practice • Likely benefit • Stage 1c or higher • Grade 3 • Clear cell histology • Uncertainty • Peri-operative rupture (surgical 1c) • Inadequate staging • Chemotherapy vs repeat staging procedure

41. Chemotherapy Advanced disease

42. Chemotherapy • Stage III & IV disease • Control cancer • Prolong life • Improve symptoms • First line • Highly effective • 70-80% response rate • Median Progression Free Survival 1-2 years • Median Overall Survival 3 years • 30% 5 year survival • Some long term survivors Palliative

43. Epithelial Ovarian Cancer • First-line chemotherapy • Carboplatin & Paclitaxel • 6 cycles - 3-weekly • Carboplatin & Paclitaxel • 18 weeks - weekly (low dose) • Carboplatin • 6 cycles - 3-weekly

44. Chemotherapy • Side effects • Fatigue • Nausea & vomiting • Myelosupression • Anaemia, risk of infection • Hair loss • Neuropathy • Mucositis • Skin & nail changes • Allergic reactions

45. Future Developments • Prevention • Risk reducing surgery for BRCA mutations • Reduced to 1% (PPC) / Breast Ca reduced 50% • Screening for early disease • Unknown • Awaiting results of UKTOCSS / UKFOCSS • Surgery • Ultra-radical or IDS

46. Future Developments • Chemotherapy • Improved systemic therapy • Increased dose intensity • Biological agents e.g. VEGF inhibitors • Improved therapy delivery • Intraperitoneal chemo

47. Future developments • Intra-peritoneal chemotherapy • Suggestion of improved survival • Increase in side effects

48. Summary • Poor prognosis due to late presentation • Early disease curable • Advanced disease treatable but not curable

49. Summary • Will NICE guidelines make any difference? • Investment in additional tests in primary care • Increase in referrals to secondary care • Improved outcomes due to earlier diagnosis? • Less likely to present with advanced cancer? • Reduced referrals to other specialties? ITS NOT IBS, ITS OVARIAN CANCER!!

50. Thank You tim.broadhead@leedsth.nhs.uk