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Ovarian Cancer Tim Broadhead Consultant Gynaecologist & Gynaecological Oncologist Ovarian Cancer • • • • • • • • Introduction Pathology Aetiology Staging Symptoms & Examination Tests Treatment Future Developments Introduction • • • • 6700 cases in UK each year 5th commonest cancer in women Lifetime risk 1 in 48 Higher incidence in postmenopausal women Introduction Poor prognosis & rarely cured • 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% • 80 Survival (%) • • 100 60 40 20 0 0 2 4 6 8 Time (years) 1090 patients Leeds Cancer Centre 1990-2005 10 Pathology • Ovarian cancer subtypes – Epithelial (90%) • • • • Serous Endometrioid Mucinous Clear cell – Germ cell tumours (10%) – Sex-cord stromal cell tumours (rare) • Primary peritoneal cancer Aetiology Most cases sporadic • “Incessant Ovulation Theory” • Pregnancy / COCP protective • Diet • Animal fat / Galactose / Alcohol • Environmental factors • Talc exposure • Hysterectomy / Tubal Ligation 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 FIGO Staging • I – confined to ovary • II – confined to pelvis FIGO Staging • III - abdominal extension or lymph nodes • IV - distant metastases Staging • Importance of stage • 5 year survival 100 Stage 1& 2 – – – – 20% Survival (%) 80 60 Stage 3 60% Stage 1 - 90% Stage 2 - 65% Stage 3 - 35% Stage 4 - 10% Stage 4 40 20% 20 0 0 2 4 6 Time (years) 8 10 1090 patients Leeds Cancer Centre 1990-2005 Symptoms “Silent Killer” •1 case every 5 years •1 every 25,000 consultations Symptoms “Ovarian cancer is not silent, rather its sound is going unheard” Symptoms Earlier diagnosis and correct pathway sooner improved survival? 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 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” 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 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) 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 Which Tests? • If CA125 >35 arrange USS abdo / pelvis Benign Malignant First tests in primary care Measure serum CA125 35 IU/ml or greater Ultrasound of abdomen and pelvis Less than 35 IU/ml Normal Suggestive of ovarian cancer Refer urgently Yes Investigate Assess carefully: are other clinical causes of symptoms apparent? No Advise to return to GP if symptoms become more frequent and/or persistent Detection in primary care Ascites and/or pelvic or abdominal mass GP assesses symptoms Tests in primary care Suspicion of ovarian cancer Urgent referral: assessment in secondary care Support and information Women presents to GP Establishing the diagnosis • CT scan Complex pelvic mass Omental cake Liver surface deposits Establishing the diagnosis • Discuss in MDT • Suspected early stage disease → local cancer unit • Advanced disease → cancer centre Treatment of Early Ovarian Cancer 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 Surgery Staging • Stage important in prognosis and treatment 100 Stage 1& 2 • 5 year survival 20% Survival (%) 80 – – – – 60 Stage 3 60% Stage 4 40 20% Stage 1 - 90% Stage 2 - 65% Stage 3 - 35% Stage 4 - 10% 20 0 0 2 4 6 Time (years) 8 10 1090 patients Leeds Cancer Centre 1990-2005 Treatment of Advanced Disease Surgery or Primary Chemotherapy? 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 Surgery for advanced disease MDT review •Disease considered resectable •Medically fit → debulking surgery 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? “Inoperable disease” Neoadjuvant Chemotherapy and Interval Debulking Surgery • • • • Disease not resectable Medically unfit Scan guided core biopsy 3 cycles chemo → IDS → 3 cycles chemo Neoadjuvant Chemotherapy and Interval Debulking Surgery • Future standard of care? • Reduced morbidity and mortality • Results of CHORUS awaited Chemotherapy Early stage disease Early stage disease • Stage I & II Died Alive Early stage disease • Stage I & II – Adjuvant Chemotherapy - Increase chance of cure Died Cured by chemo Alive ICON1/Action: JNCI 2003 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 Chemotherapy Advanced disease Chemotherapy • Stage III & IV disease – Control cancer – Prolong life – Improve symptoms Palliative – 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 Epithelial Ovarian Cancer • First-line chemotherapy – Carboplatin & Paclitaxel • 6 cycles - 3-weekly – Carboplatin & Paclitaxel • 18 weeks - weekly (low dose) – Carboplatin • 6 cycles - 3-weekly Chemotherapy • Side effects – Fatigue – Nausea & vomiting – Myelosupression • Anaemia, risk of infection – Hair loss – Neuropathy – Mucositis – Skin & nail changes – Allergic reactions 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 Future Developments • Chemotherapy • Improved systemic therapy – Increased dose intensity – Biological agents e.g. VEGF inhibitors • Improved therapy delivery – Intraperitoneal chemo Future developments • Intra-peritoneal chemotherapy • Suggestion of improved survival • Increase in side effects Summary • Poor prognosis due to late presentation • Early disease curable • Advanced disease treatable but not curable 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!! Thank You [email protected]