Is there a role for ovarian cancer screening


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Ovarian cancer is the second most common cancer in the female genital tract. Most of the cases are detected late and thus their survival rate is low. This presentation will tell you on the role of ovarian cancer screening based on the current available evidence.

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Is there a role for ovarian cancer screening

  1. 1. Is there a role for ovarian cancer screening? O&G Dept CME 29 Nov 2013 Dr Voon Hian Yan Supervisor: Dr Sim Wee Wee
  2. 2. What do they have in common?
  3. 3. 7 Commandments on Screening Adapted by WHO after Wilson and Jungner Significant prevalance and severity Fixed spectrum of symptoms Tests which are simple and acceptable to the patient Accurate screening test Confirmatory test available Treatable disease Favourable cost/benefit ratio Screening is done where direct diagnostic tests are costly/invasive / requires specialised personnel or equipment / greater risk to patient
  4. 4. Burden of Ovarian cancer 2nd most common cancer of the female genital tract 5th most common cancer in females 7000 women in the UK are diagnosed with ovarian cancer/yr 8 in 10 are diagnosed in women >50yrs old Incidence: 17 in 100,000 Lifetime risk: 1 in 71 No identifiable premalignant stages ex CIN 5yr survival 94% if detected in Stage I (15% ) Majority 60% are detected late with 5 yr survival 28%
  5. 5. Incessant ovulation Inflammation
  6. 6. How and who to screen? HOW Tumor markers: Ca-125 -only 50% stage I and II epithelial ovarian cancers -only 80% of epithelial ovarian cancers -false +ve esp in younger women Imaging : TVS (patient acceptability, skilled operator) WHO Post-menopausal women General population vs high risk groups
  7. 7. Is there a role of Ca125 or Ultrasound screening? Effect of Screening on Ovarian Cancer Mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial JAMA. 2011;305(22):2295-2303. doi:10.1001/jama.2011.766
  8. 8. Target group Postmenopausal women
  9. 9. PLCO: Ovarian cancer mortality cancers deaths
  10. 10. Mortality rates were similar between both groups Intervention group (screened) 118 deaths 3.1 er 10,000 person years Usual care group 100 deaths 2.6 per 10,000 person years (mortality RR, 1.18; 95% CI, 0.91-1.54 [unadjusted] ) (mortality RR, 1.18; 95% CI, 0.82-1.71 [sequentially adjusted])
  11. 11. Stage at detection, histology of ovarian cancers detected and treatment needed did not differ
  12. 12. Screening-related harms: Minor Bruising or Fainting 58.3 in 10,000 Ca125 3.3 in 10,000 TVS
  13. 13. Screening-related harms 3285 false positive (5%),1080 (33%) of whom needed surgery Major complication rate of 20/100 (some women had >1 complication) Oophrectomy rates were 33% higher in intervention (85/10000) vs control (64/10,000)
  14. 14. Author's conclusion "Annual screening for ovarian cancer as performed in the PLCO trial with simultaneous CA-125 and transvaginal ultrasound does not reduce disease-specific mortality in women at average risk for ovarian cancer but does increase invasive medical procedures and associated harms"
  15. 15. Other population cohorts UKTOCS 200,000 (largest) ;50-74yrs old 70,000 (=PLCO); median 58yrs Multimodal (annual Ca125 +/- TVS) N Shizuoka Cohort Study of ovarian cancer screening Annual TVS+CA125 Screening strategies Annual TVS Control Multimodal= 42 cancers Annual TVS= 45 cancers Preliminary results *Overall 48% detected in stage I or II, no difference in stage distribution in both groups Control Intervention= 35 cancers detected after a mean period of 9yrs Control= 32 cancers *Results from controls not released yet Significant withdrawal rate 5% in USS and 1% in MMS group ?Acceptability of TVS as a screening modality Mortality benefit Pending (trial completes in 2014) Pending (trial completed)
  16. 16. Screening in the high risk population
  17. 17. Before and after
  18. 18. BRCA-1/BRCA-2/HNPCC BRCA1-/BRCA-2 Prophylactic BSO reduces lifetime risk of ovarian cancer from 40% to 1-2% Reduces risk of breast cancer by 50% Reduces risk of recurrent breast cancer if previously diagnosed Risk of primary peritoneal cancer reduced 1% per year to 0.2% per year (4% up to 20yrs after BSO)
  19. 19. Rarer famillial ovarian cancer syndromes Muir-Torre syndrome (MTS) - sebaceous skin tumorss, colorectal, ovarian, endometrial Turcot syndrome -colorectal, CNS tumors, endometrial, ovarian
  20. 20. UKFOCSS UK Familial Ovarian Cancer Screening Study 2002-2010 Overview -Over 3500 women between 35-75 yrs old -> 10% lifetime risk of developing ovarian cancer -yearly Ca125 and TVS Results -14 of 37 women (38%) diagnosed with Stage I or II -23 of 37 women (62%) diagnosed with Stage III or IV Conclusion Gap between screening may have impact on stage at diagnosis. Interval > 1 year more likely to have advanced cancer at diagnosis
  21. 21. Phase II UKFOCSS Will increased screening interval improve stage at detection? 4 monthly screening
  22. 22. So............... is there a role in Ovarian Cancer Screening? 1) Low risk population -Does not increase the detection of early stage ovarian cancer or alter treatment rendered - No statistically significant change in mortality - Increased intervention (33% more oophrectomies) and complications (1 in 5), especially in false positive cases 2) High risk population -Awaiting outcome of Phase II UKFOCSS -Genetic screening instead?
  23. 23. Is there a role for Ovarian Cancer screening? 3) Type of tumor markers Nested trials within the PLCO did not show any increase in sensitivity with -HE4 -transthyretin -CA15.3 / CA72.4 -apolipoprotein A1 -transferrin -hepcidin -beta-2 microglobulin -connective tissue activating protein III -inter-alpha-trypsin inhibitor heavy-chain 4) Serial rather than single Ca125 value? "Ca125 trajectory"
  24. 24. HE-4 Raised in 50% of epithelial ovarian tumours that do not express Ca125 Highly specific, allowing it to differentiate benign from malignant tumors Greater sensitivity than with Ca125 alone in detecting early stage ovarian cancers
  25. 25. References Sueblinvong T, Carney ME. Current of risk factors for ovarian cancer. Current Treatment Options in Oncology 2009;10:67-81 Devlin LA and PJ Morrison PJ. Inherited gynaecological cancer syndromes. TOG 10.1576/toag. 2008;10:9–15 Darnforth KN et al. Addendum to Screening for Ovarian Cancer: Evidence Update for the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement. AHRQ Publication No. 12-05165-EF4 April 2012 Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295-303
  26. 26. References Menon U, Gentry-Maharaj A, Hallett R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009;10(4):327-40.
  27. 27. THANK YOU
  28. 28. Limitations PLCO The trial was powered for a 35% mortality reduction based on a predicted number of mortality events (n = 226) that was essentially met. However, from a public health point of view, smaller effect sizes are still potentially worthwhile to detect. The sequentially adjusted lower 95% CI for the mortality RR was 0.82, indicating at most an 18% relative benefit within the limits of reasonable probability. ( Ci was 0.82-1.71) Additionally, the data collected on treatment were somewhat limited. The PLCO trial neither abstracted the type of systemic therapy used, nor the type of surgeon who performed the oophorectomy (eg, gynecologic oncologist or not); both factors have been shown to be related to ovarian cancer survival. However, we have no reason to suppose that these factors differed by study group.