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Whether this null result reflects the stop-screen design, screening performance, or ovarian cancer natural history remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using individual-level screening and diagnosis data from the MMS arm, we estimated ovarian cancer natural history, focusing on high-grade serous ovarian cancer (HGSC), the most common and lethal subtype. We then simulated trial outcomes under (1) continued screening beyond the trial screening interval and (2) high sensitivity for early-stage detection over an extended time period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The estimated window for detecting early-stage HGSC under MMS was &lt;6 months. Continued screening yielded at most a 15% relative mortality reduction. Achieving a\u2009\u226520% mortality reduction required extending the detectable early-stage window to 1 year and attaining \u226570% sensitivity during this period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Current screening modalities offer a very limited opportunity to intercept HGSC at an early stage. Clinically effective ovarian cancer screening will require first- and second-line tests capable of detecting HGSC substantially earlier in its natural history.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03490-2","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T12:53:15Z","timestamp":1781355195000},"page":"890-896","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Can ovarian cancer screening work? A secondary analysis of the UK collaborative trial of ovarian cancer screening"],"prefix":"10.1038","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0014-9679","authenticated-orcid":false,"given":"Jane M.","family":"Lange","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishfaq","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel J.","family":"Dengos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Apostolidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Gentry-Maharaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Holloway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4990-0849","authenticated-orcid":false,"given":"Marc D.","family":"Ryser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3708-1732","authenticated-orcid":false,"given":"Usha","family":"Menon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Etzioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"3490_CR1","first-page":"225","volume":"59","author":"A Jemal","year":"2009","unstructured":"Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. 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(May 2024\u2013March 2025). UM has research grants paid to the institution from Intelligent Lab on Fibre, RNA Guardian, MercyBio Analytics and CleoDx related to early detection of ovarian cancer. JL has consulted for GRAIL and Guardant Health unrelated to this work.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}