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<p>Precision healthcare aims to tailor disease prevention and early detection to individual risk. Prostate cancer screening may benefit from genomics-informed approaches. We developed and validated the P-CARE model, a prostate cancer risk prediction tool combining a polygenic score, family history and genetic ancestry, using data from over 585,000 male participants in the Million Veteran Program. The model was externally validated in diverse cohorts and implemented via a blended genome–exome assay for clinical use. Here we show that the P-CARE model identifies clinically meaningful gradients of prostate cancer risk among men, with higher scores associated with increased risk of any, metastatic and fatal prostate cancer. The model is now being used in a clinical trial of precision prostate cancer screening. This work demonstrates the potential for genomics-enabled health systems to improve prostate cancer screening and prevention in men. ClinicalTrials.gov registration: <a href="http://clinicaltrials.gov/ct2/show/NCT05926102">NCT05926102</a>.</p>

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Genomic risk model to implement precision prostate cancer screening in clinical care: the ProGRESS study

  • 期刊论文

  • 发表日期：

    2026年1月26日

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  • Jason L. Vassy,
  • Anna M. Dornisch,
  • Roshan Karunamuni,
  • Michael Gatzen,
  • Christopher J. Kachulis,
  • Niall J. Lennon,
  • Charles A. Brunette,
  • Morgan E. Danowski,
  • Richard L. Hauger,
  • Isla P. Garraway,
  • Adam S. Kibel,
  • Kyung M. Lee,
  • Julie A. Lynch,
  • Kara N. Maxwell,
  • Dmitry Ratner,
  • Brent S. Rose,
  • Craig C. Teerlink,
  • George J. Xu,
  • Sean E. Hofherr,
  • Katherine A. Lafferty,
  • Katie Larkin,
  • Edyta Malolepsza,
  • Candace J. Patterson,
  • Diana M. Toledo,
  • Jenny L. Donovan,
  • Freddie C. Hamdy,
  • Richard M. Martin,
  • David E. Neal,
  • Emma L. Turner,
  • Ole A. Andreassen,
  • Anders M. Dale,
  • Ian G. Mills,
  • Aswin Abraham,
  • Jyotsna Batra,
  • Judith Clements,
  • Olivier Cussenot,
  • Cezary Cybulski,
  • Rosalind A. Eeles,
  • Jay H. Fowke,
  • Eli Marie Grindedal,
  • Henrik Grönberg,
  • Robert J. Hamilton,
  • Jasmine Lim,
  • Yong-Jie Lu,
  • Robert J. MacInnis,
  • Christiane Maier,
  • Lorelei A. Mucci,
  • Luc Multigner,
  • Susan L. Neuhausen,
  • Sune F. Nielsen,
  • Marie-Élise Parent,
  • Jong Y. Park,
  • Gyorgy Petrovics,
  • Anna Plym,
  • Azad Razack,
  • Barry S. Rosenstein,
  • Johanna Schleutker,
  • Karina Dalsgaard Sørensen,
  • Paul A. Townsend,
  • Ruth C. Travis,
  • Ana Vega,
  • Catharine M. L. West,
  • Fredrik Wiklund,
  • Wei Zheng,
  • Rosalind A. Eeles,
  • Elizabeth K. Bancroft,
  • Eva McGrowder,
  • Zsofia Kote-Jarai,
  • Mark N. Brook,
  • Elizabeth C. Page,
  • Jana McHugh,
  • Holly Ni Raghallaigh,
  • Denzil James,
  • Pardeep Kumar,
  • Steve Hazell,
  • Aslam Sohaib,
  • Alexander Dias,
  • Christos Mikropoulos,
  • Netty Kinsella,
  • Declan Cahill,
  • Elizabeth K. Bancroft,
  • Elizabeth C. Page,
  • D. Gareth Evans,
  • Geoffrey J. Lindeman,
  • Paul James,
  • Lucy Side,
  • Karina Rønlund,
  • Brian T. Helfand,
  • Cezary Cybulski,
  • Kai-Ren Ong,
  • Monica Salinas,
  • Jackie Cook,
  • Kara Maxwell,
  • Manuel R. Teixeira,
  • Rosemarie Davidson,
  • Annelie Liljegren,
  • Ashraf Azzabi,
  • Marc Tischkowitz,
  • Ruth Cleaver,
  • Julian Barwell,
  • Neil K. Aaronson,
  • Audrey Ardern-Jones,
  • Chris H. Bangma,
  • Elena Castro,
  • David Dearnaley,
  • Diana M. Eccles,
  • Alison Falconer,
  • Henrik Gronberg,
  • Freddie C. Hamdy,
  • Vincent Khoo,
  • Hans Lilja,
  • Jan Lubinski,
  • Christos Mikropoulos,
  • Anita Mitra,
  • Judith Offman,
  • Gad Rennert,
  • Mohnish Suri,
  • Christopher A. Haiman,
  • Zsofia Kote-Jarai,
  • Fredrick R. Schumacher,
  • Sara Benlloch,
  • Ali Amin Al Olama,
  • Kenneth R. Muir,
  • Sonja I. Berndt,
  • David V. Conti,
  • Fredrik Wiklund,
  • Stephen Chanock,
  • Ying Wang,
  • Catherine M. Tangen,
  • Henrik Grönberg,
  • Nora Pashayan,
  • Demetrius Albanes,
  • Stephanie J. Weinstein,
  • Alicja Wolk,
  • Catharine M. L. West,
  • Géraldine Cancel-Tassin,
  • Stella Koutros,
  • David E. Neal,
  • Freddie C. Hamdy,
  • Robert J. Hamilton,
  • Sue Ann Ingles,
  • Barry S. Rosenstein,
  • Yong-Jie Lu,
  • Graham G. Giles,
  • Robert J. MacInnis,
  • Adam S. Kibel,
  • Manolis Kogevinas,
  • Kathryn L. Penney,
  • Janet L. Stanford,
  • Børge G. Nordestgaard,
  • Sune F. Nielsen,
  • Hermann Brenner,
  • Christiane Maier,
  • Jeri Kim,
  • Esther M. John,
  • Manuel R. Teixeira,
  • Kim De Ruyck,
  • Lisa F. Newcomb,
  • Davor Lessel,
  • Radka Kaneva,
  • Nawaid Usmani,
  • Frank Claessens,
  • Paul A. Townsend,
  • Jose Esteban Castelao,
  • Monique J. Roobol,
  • Florence Menegaux,
  • Kay-Tee Khaw,
  • Lisa Cannon-Albright,
  • Hardev Pandha,
  • Stephen N. Thibodeau,
  • David J. Hunter,
  • Peter Kraft,
  • William J. Blot,
  • Elio Riboli,
  • Sumitra Muralidhar,
  • Jennifer Moser,
  • Jennifer E. Deen,
  • Philip S. Tsao,
  • J. Michael Gaziano,
  • Adriana Hung,
  • Dave Oslin,
  • Deepak Voora,
  • Jessica V. Brewer,
  • Mary T. Brophy,
  • Kelly Cho,
  • Lori Churby,
  • Jacob T. Kean,
  • Saiju Pyarajan,
  • Robert Ringer,
  • Luis E. Selva,
  • Shahpoor Alex Shayan,
  • Brady Stephens,
  • Stacey B. Whitbourne,
  • Tyler M. Seibert

摘要

Precision healthcare aims to tailor disease prevention and early detection to individual risk. Prostate cancer screening may benefit from genomics-informed approaches. We developed and validated the P-CARE model, a prostate cancer risk prediction tool combining a polygenic score, family history and genetic ancestry, using data from over 585,000 male participants in the Million Veteran Program. The model was externally validated in diverse cohorts and implemented via a blended genome–exome assay for clinical use. Here we show that the P-CARE model identifies clinically meaningful gradients of prostate cancer risk among men, with higher scores associated with increased risk of any, metastatic and fatal prostate cancer. The model is now being used in a clinical trial of precision prostate cancer screening. This work demonstrates the potential for genomics-enabled health systems to improve prostate cancer screening and prevention in men. ClinicalTrials.gov registration: NCT05926102.