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Would ovarian cancer screening improve survival rates? Holly HainesOvarian Cancer • Stage 1 – 93.3% • Stage 4 – 13.4% 2 1-Year 5-Year 120 100 80 % ( T R L 60 V V R S 40 20 0 1 2 3 4 STAGE OF OC One- and Five-Year Age-Standardised Net OC Survival Rate for Ages 15-99 by Stage at Diagnosis, England 3Overview • Objectives • Results • Objective 1 • Objective 2 • Objective 3 • Project Conclusions • Future Steps 4Objectives 51. Screening Method Efficacy 2. High Risk Populations 3. Screening Risks 67Results 8Randomised Controlled Trials • PLCO trial articles (4) • UKCTOCS trial articles (3) • Other articles (5) Total: 12 9PLCO Trial • Prostate, Lung, Colorectal, & Ovarian Cancer Trial • American • 68,557 analysed • 2 groups 10UKCTOCS • UK Collaborative Trial of Ovarian Cancer Screening • 193,408 analysed • 3 groups 11 Objective 1: Screening Method Efficacy 12Measuring Screening Methods • Sensitivity • Specificity 13Methods • Blood tests • Diagnostic algorithms • Ultrasound 14Blood Tests • CA125 highest sensitivity • With HE4 • More positive screens 15Algorithms - ROCA • Velocity based • Significant sensitivity compared to CA125 16Ultrasound • UKCTOCS • High sensitivity & specificity • No mortality reduction 17Multimodal • Specificity > USS • UKCTOCS • Stage shift • Jacobs et al. • Survival increase 18Multimodal • Specificity > USS • UKCTOCS • Stage shift No mortality reduction… • Jacobs et al. • Survival increase WHY? 192021 Objective 2: High Risk Populations 22Risk Factors • Age • BRCA1/2 23PLCO Trial Subgroup • FDR with breast/OC history • Stage shift • Survival increase • No mortality reduction 24 Objective 3: Screening Risks 25False Positives & Surgery • Invasive follow up procedures • 1/3 had surgery (PLCO) • Most with TVS • Major surgical complications • 15% PLCO • 3% UKCTOCS • 9% Menon et al. (2005) 26Project Conclusions 27• ROCA used in MMS • Increased familial risk • No mortality most effective more promising reductions • Survival & stage shifts • Role of bias greatest Therefore... 28General population screening cannot be recommended at this time. 29Future Steps 30Trials • UK Familial Ovarian Cancer Screening Study • Risk reducing salpingo-oophorectomy • Screening for circulating tumour cells or cell-free DNA 31References 1 1. American Cancer Society. Ovarian Cancer Stages [Internet]. 2018 [updated 2018 Apr 11; cited 2023 Feb 19]. Available from: https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/staging.html 2. American Cancer Society. Ovarian Cancer Risk Factors [Internet]. 2021 [updated 2021 Jan 26; cited 2023 Feb 01]. Available from: https://www.cancer.org/cancer/ovarian-cancer/causes-risks-prevention/risk-factors.html 3. Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, Reding DJ, Greenlee RT, Yokochi LA, Kessel B, Crawford ED, Church TR, Andriole GL, Weissfeld JL, Fouad MN, Chia D, O'Brien B, Ragard LR, Clapp JD, Rathmell JM, Riley TL, Hartge P, Pinsky PF, Zhu CS, Izmirlian G, Kramer BS, Miller AB, Xu JL, Prorok PC, Gohagan JK, Berg CD. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA [Internet]. 2011 [cited 2023 Feb 22]; 305(22): 2295-2303. Available from: https://pubmed.ncbi.nlm.nih.gov/21642681/ doi: 10.1001/jama.2011.766 4. Cancer Research UK. Ovarian cancer statistics [Internet]. 2023 [cited 2023 Jan 30]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer#heading-Zero 5. Cramer DW, Bast Jr RC, Berg CD, Diamandis EP, Godwin AK, Hartge P, et al. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res [Internet]. 2011 [cited 2023 Feb 22]; 4(3): 365-374. Available from: https://pubmed.ncbi.nlm.nih.gov/21372036/ doi: 10.1158/1940-6207.CAPR-10-0195 6. Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet [Internet]. 2016 [cited 2023 Feb 28]; 387(10022): 945-956. Available from: https://pubmed.ncbi.nlm.nih.gov/26707054/ doi: 10.1016/S0140-6736(15)01224-6 7. Jacobs IJ, Skates SJ, MacDonald N, Menon U, Rosenthal AN, Davies AP, Woolas R, Jeyarajah AR, Sibley K, Lowe DG, Oram DH. Screening for ovarian cancer: a pilot randomised controlled trial. Lancet [Internet]. 1999 [cited 2023 Feb 22]; 353(9160): 1207- 1210. Available from: https://pubmed.ncbi.nlm.nih.gov/10217079/ doi: 10.1016/S0140-6736(98)10261-1 8. Karlan BY, Thorpe J, Watabayashi K, Drescher CW, Palomares M, Daly MB, Paley P, Hillard P, Anderson MR, Anderson G, Drapkin R, Urban N. Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women. Cancer Epidemiol Biomarkers Prev [Internet]. 2014 [cited 2023 Feb 22]; 23(7): 1383-1393. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082470/ doi: 10.1158/1055-9965.EPI- 13-1361 9. Kobayashi H, Yamada Y, Sado T, Sakata M, Yoshida S, Kawaguchi R, Kanayama S, Shigetomi H, Haruta S, Tsuji Y, Ueda S, Kitanaka T. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer [Internet]. 2008 [cited 2023 Feb 22]; 18(3): 414-420. Available from: https://pubmed.ncbi.nlm.nih.gov/17645503/ doi: 10.1111/j.1525-1438.2007.01035.x 10. Lai T, Kessel B, Ahn HJ, Terada KY. Ovarian cancer screening in menopausal females with a family history of breast or ovarian cancer. J Gynecol Oncol [Internet]. 2016 [cited 2023 Feb 28]; 27(4): 41-49. Available from: https://pubmed.ncbi.nlm.nih.gov/27102249/ doi: 10.3802/jgo.2016.27.e41 32References 2 11. Menon U, Gentry-Maharaj A, Burnell M, Singh N, Ryan A, Karpinskyj C, et al. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet [Internet]. 2021 [cited 2023 Feb 05]; 397(10290): 2182-2193. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33991479 doi: 10.1016/S0140-6736(21)00731-5 12. Menon U, Ryan A, Kalsi J, Gentry-Maharaj A, Dawnay A, Habib M, et al. Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. J Clin Oncol [Internet]. 2015 [cited 2023 Feb 28]; 33(18): 2062-2071. Available from: https://pubmed.ncbi.nlm.nih.gov/25964255/ doi: 10.1200/JCO.2014.59.4945 13. Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, Lewis S, Davies S, Philpott S, Lopes A, Godfrey K, Oram D, Herod J, Williamson K, Seif MW, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso NN, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Singh N, Dawnay A, Skates SJ, Parmar M, Jacobs I. 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 [Internet]. 2009 [cited 2023 Feb 22]; 10(4): 327-340. Available from: https://pubmed.ncbi.nlm.nih.gov/19282241/ doi: 10.1016/S1470-2045(09)70026-9 14. Menon U, Skates SJ, Lewis S, Rosenthal AN, Rufford B, Sibley K, Macdonald N, Dawnay A, Jeyarajah A, Bast RC Jr, Oram D, Jacobs IJ. Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. J Clin Oncol [Internet]. 2005 [cited 2023 Feb 22]; 23(31): 7919-7926. Available from: https://pubmed.ncbi.nlm.nih.gov/16258091/ doi: 10.1200/JCO.2005.01.6642 15. National Health Service. Ovarian cancer. [Internet] 2023 [cited 2023 Jan 30]. Available from: https://www.nhs.uk/conditions/ovarian-cancer/ 16. Office for National Statistics. Cancer survival in England - adults diagnosed [Internet]. 2019 [cited 2023 Jan 30]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancersurvivalratescancersurvivalinenglandadultsdiagnosed 17. Patz Jr EF, Goodman PC, Bepler G. Screening for lung cancer. N Engl J Med [Internet]. 2000 [cited 2023 Mar 26]; 343(22): 1627-1633. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11096172 doi: 10.1056/NEJM200011303432208 18. Pinsky PF, Yu K, Kramer BS, Black A, Buys SS, Partridge E, et al. Extended mortality results for ovarian cancer screening in the PLCO trial with median 15 years follow-up. Gynecol Oncol [Internet]. 2016 [cited 2023 Feb 28]; 143(2): 270-275. Available from: https://pubmed.ncbi.nlm.nih.gov/27615399/ doi: 10.1016/j.ygyno.2016.08.334 19. Rufford BD, Jacobs IJ, Menon U. Feasibility of screening for ovarian cancer using symptoms as selection criteria. BJOG [Internet]. 2007 [cited 2023 Feb 22]; 114(1): 59-64. Available from: https://pubmed.ncbi.nlm.nih.gov/17233861/ doi: 10.1111/j.1471- 0528.2006.01153.x 20. Temkin SM, Miller EA, Samimi G, Berg CD, Pinsky P, Minasian L. Outcomes from ovarian cancer screening in the PLCO trial: Histologic heterogeneity impacts detection, overdiagnosis and survival. Eur J Cancer [Internet]. 2017 [cited 2023 Feb 22]; 87:187- 198. Available from: https://pubmed.ncbi.nlm.nih.gov/29156299/ doi: 10.1016/j.ejca.2017.10.015 21. WHO. Screening programmes: a short guide. Increase effectiveness, maximize benefits and minimize harm [Internet]. Copenhagen: WHO Regional Office for Europe. 2020 [cited 2023 Feb 14]. 70. Available from: 33 https://apps.who.int/iris/bitstream/handle/10665/330829/9789289054782-eng.pdfQuestions? Holly Haines