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

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 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; Tyler M. Seibert; Profile Steering Committee; IMPACT Study Steering Committee and Collaborators; PRACTICAL consortium; VA Million Veteran Program

doi:10.1038/s43018-025-01103-0

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

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 Maxwell, Dmitry Ratner, Brent S. Rose, Craig C. Teerlink, George J. Xu, Sean E. Hofherr, Katherine A. LaffertyKatie 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, Tyler M. Seibert^*, Profile Steering Committee, IMPACT Study Steering Committee and Collaborators, PRACTICAL consortium, VA Million Veteran Program

^*Corresponding author af dette arbejde

Klinisk Biokemisk Afdeling HGH

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Nature Cancer
DOI	https://doi.org/10.1038/s43018-025-01103-0
Status	Accepteret/In press - 2026

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10.1038/s43018-025-01103-0

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Vassy, J. L., Dornisch, A. M., Karunamuni, R., Gatzen, M., Kachulis, C. J., Lennon, N. J., Brunette, C. A., Danowski, M. E., Hauger, R. L., Garraway, I. P., Kibel, A. S., Lee, K. M., Lynch, J. A., Maxwell, K., Ratner, D., Rose, B. S., Teerlink, C. C., Xu, G. J., Hofherr, S. E., ... VA Million Veteran Program (Accepteret/In press). Genomic risk model to implement precision prostate cancer screening in clinical care: the ProGRESS study. Nature Cancer. https://doi.org/10.1038/s43018-025-01103-0

Vassy, JL, Dornisch, AM, Karunamuni, R, Gatzen, M, Kachulis, CJ, Lennon, NJ, Brunette, CA, Danowski, ME, Hauger, RL, Garraway, IP, Kibel, AS, Lee, KM, Lynch, JA, Maxwell, K, Ratner, D, Rose, BS, Teerlink, CC, Xu, GJ, Hofherr, SE, Lafferty, KA, Larkin, K, Malolepsza, E, Patterson, CJ, Toledo, DM, Donovan, JL, Hamdy, FC, Martin, RM, Neal, DE, Turner, EL, Andreassen, OA, Dale, AM, Mills, IG, Abraham, A, Batra, J, Clements, J, Cussenot, O, Cybulski, C, Eeles, RA, Fowke, JH, Grindedal, EM, Grönberg, H, Hamilton, RJ, Lim, J, Lu, YJ, MacInnis, RJ, Maier, C, Mucci, LA, Multigner, L, Neuhausen, SL, Nielsen, SF, Parent, MÉ, Park, JY, Petrovics, G, Plym, A, Razack, A, Rosenstein, BS, Schleutker, J, Sørensen, KD, Townsend, PA, Travis, RC, Vega, A, West, CML, Wiklund, F, Zheng, W, Seibert, TM, Profile Steering Committee, IMPACT Study Steering Committee and Collaborators, PRACTICAL consortium & VA Million Veteran Program 2026, 'Genomic risk model to implement precision prostate cancer screening in clinical care: the ProGRESS study', Nature Cancer. https://doi.org/10.1038/s43018-025-01103-0

@article{92770cc0c55c48aba18c571360b384be,

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

abstract = "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.",

author = "Vassy, \{Jason L.\} and Dornisch, \{Anna M.\} and Roshan Karunamuni and Michael Gatzen and Kachulis, \{Christopher J.\} and Lennon, \{Niall J.\} and Brunette, \{Charles A.\} and Danowski, \{Morgan E.\} and Hauger, \{Richard L.\} and Garraway, \{Isla P.\} and Kibel, \{Adam S.\} and Lee, \{Kyung M.\} and Lynch, \{Julie A.\} and Kara Maxwell and Dmitry Ratner and Rose, \{Brent S.\} and Teerlink, \{Craig C.\} and Xu, \{George J.\} and Hofherr, \{Sean E.\} and Lafferty, \{Katherine A.\} and Katie Larkin and Edyta Malolepsza and Patterson, \{Candace J.\} and Toledo, \{Diana M.\} and Donovan, \{Jenny L.\} and Hamdy, \{Freddie C.\} and Martin, \{Richard M.\} and Neal, \{David E.\} and Turner, \{Emma L.\} and Andreassen, \{Ole A.\} and Dale, \{Anders M.\} and Mills, \{Ian G.\} and Aswin Abraham and Jyotsna Batra and Judith Clements and Olivier Cussenot and Cezary Cybulski and Eeles, \{Rosalind A.\} and Fowke, \{Jay H.\} and Grindedal, \{Eli Marie\} and Henrik Gr{\"o}nberg and Hamilton, \{Robert J.\} and Jasmine Lim and Lu, \{Yong Jie\} and MacInnis, \{Robert J.\} and Christiane Maier and Mucci, \{Lorelei A.\} and Luc Multigner and Neuhausen, \{Susan L.\} and Nielsen, \{Sune F.\} and Parent, \{Marie {\'E}lise\} and Park, \{Jong Y.\} and Gyorgy Petrovics and Anna Plym and Azad Razack and Rosenstein, \{Barry S.\} and Johanna Schleutker and S{\o}rensen, \{Karina Dalsgaard\} and Townsend, \{Paul A.\} and Travis, \{Ruth C.\} and Ana Vega and West, \{Catharine M.L.\} and Fredrik Wiklund and Wei Zheng and Nordestgaard, \{B{\o}rge G.\} and Seibert, \{Tyler M.\} and \{Profile Steering Committee\} and \{IMPACT Study Steering Committee and Collaborators\} and \{PRACTICAL consortium\} and \{VA Million Veteran Program\}",

note = "Publisher Copyright: {\textcopyright} This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2026.",

year = "2026",

doi = "10.1038/s43018-025-01103-0",

language = "English",

journal = "Nature Cancer",

issn = "2662-1347",

publisher = "Nature Research",

}

TY - JOUR

T1 - Genomic risk model to implement precision prostate cancer screening in clinical care

T2 - the ProGRESS study

AU - Vassy, Jason L.

AU - Dornisch, Anna M.

AU - Karunamuni, Roshan

AU - Gatzen, Michael

AU - Kachulis, Christopher J.

AU - Lennon, Niall J.

AU - Brunette, Charles A.

AU - Danowski, Morgan E.

AU - Hauger, Richard L.

AU - Garraway, Isla P.

AU - Kibel, Adam S.

AU - Lee, Kyung M.

AU - Lynch, Julie A.

AU - Maxwell, Kara

AU - Ratner, Dmitry

AU - Rose, Brent S.

AU - Teerlink, Craig C.

AU - Xu, George J.

AU - Hofherr, Sean E.

AU - Lafferty, Katherine A.

AU - Larkin, Katie

AU - Malolepsza, Edyta

AU - Patterson, Candace J.

AU - Toledo, Diana M.

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Martin, Richard M.

AU - Neal, David E.

AU - Turner, Emma L.

AU - Andreassen, Ole A.

AU - Dale, Anders M.

AU - Mills, Ian G.

AU - Abraham, Aswin

AU - Batra, Jyotsna

AU - Clements, Judith

AU - Cussenot, Olivier

AU - Cybulski, Cezary

AU - Eeles, Rosalind A.

AU - Fowke, Jay H.

AU - Grindedal, Eli Marie

AU - Grönberg, Henrik

AU - Hamilton, Robert J.

AU - Lim, Jasmine

AU - Lu, Yong Jie

AU - MacInnis, Robert J.

AU - Maier, Christiane

AU - Mucci, Lorelei A.

AU - Multigner, Luc

AU - Neuhausen, Susan L.

AU - Nielsen, Sune F.

AU - Parent, Marie Élise

AU - Park, Jong Y.

AU - Petrovics, Gyorgy

AU - Plym, Anna

AU - Razack, Azad

AU - Rosenstein, Barry S.

AU - Schleutker, Johanna

AU - Sørensen, Karina Dalsgaard

AU - Townsend, Paul A.

AU - Travis, Ruth C.

AU - Vega, Ana

AU - West, Catharine M.L.

AU - Wiklund, Fredrik

AU - Zheng, Wei

AU - Seibert, Tyler M.

AU - Profile Steering Committee

AU - IMPACT Study Steering Committee and Collaborators

AU - PRACTICAL consortium

AU - VA Million Veteran Program

A2 - Nordestgaard, Børge G.

PY - 2026

Y1 - 2026

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105029479515

U2 - 10.1038/s43018-025-01103-0

DO - 10.1038/s43018-025-01103-0

M3 - Journal article

C2 - 41588240

AN - SCOPUS:105029479515

SN - 2662-1347

JO - Nature Cancer

JF - Nature Cancer

ER -

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

Abstract

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