BACKGROUND: A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. METHODS: The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. RESULTS: In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10-5). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). CONCLUSIONS: The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS.
BACKGROUND: A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. METHODS: The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. RESULTS: In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10-5). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). CONCLUSIONS: The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS.
Authors: Ian Thompson; James Brantley Thrasher; Gunnar Aus; Arthur L Burnett; Edith D Canby-Hagino; Michael S Cookson; Anthony V D'Amico; Roger R Dmochowski; David T Eton; Jeffrey D Forman; S Larry Goldenberg; Javier Hernandez; Celestia S Higano; Stephen R Kraus; Judd W Moul; Catherine M Tangen Journal: J Urol Date: 2007-06 Impact factor: 7.450
Authors: Timothy J Wilt; Michael K Brawer; Karen M Jones; Michael J Barry; William J Aronson; Steven Fox; Jeffrey R Gingrich; John T Wei; Patricia Gilhooly; B Mayer Grob; Imad Nsouli; Padmini Iyer; Ruben Cartagena; Glenn Snider; Claus Roehrborn; Roohollah Sharifi; William Blank; Parikshit Pandya; Gerald L Andriole; Daniel Culkin; Thomas Wheeler Journal: N Engl J Med Date: 2012-07-19 Impact factor: 91.245
Authors: Matthew R Cooperberg; David J Pasta; Eric P Elkin; Mark S Litwin; David M Latini; Janeen Du Chane; Peter R Carroll Journal: J Urol Date: 2005-06 Impact factor: 7.450
Authors: Marc A Dall'Era; Peter C Albertsen; Christopher Bangma; Peter R Carroll; H Ballentine Carter; Matthew R Cooperberg; Stephen J Freedland; Laurence H Klotz; Christopher Parker; Mark S Soloway Journal: Eur Urol Date: 2012-06-07 Impact factor: 20.096
Authors: J Cuzick; D M Berney; G Fisher; D Mesher; H Møller; J E Reid; M Perry; J Park; A Younus; A Gutin; C S Foster; P Scardino; J S Lanchbury; S Stone Journal: Br J Cancer Date: 2012-02-23 Impact factor: 7.640
Authors: J Cuzick; S Stone; G Fisher; Z H Yang; B V North; D M Berney; L Beltran; D Greenberg; H Møller; J E Reid; A Gutin; J S Lanchbury; M Brawer; P Scardino Journal: Br J Cancer Date: 2015-06-23 Impact factor: 7.640
Authors: Jonathan C Hu; Jeffrey J Tosoian; Ji Qi; Deborah Kaye; Anna Johnson; Susan Linsell; James E Montie; Khurshid R Ghani; David C Miller; Kirk Wojno; Frank N Burks; Daniel E Spratt; Todd M Morgan Journal: JCO Precis Oncol Date: 2018-10-19
Authors: Eoin Dinneen; Gregory L Shaw; Roseann Kealy; Panos Alexandris; Kier Finnegan; Kimberley Chu; Nadia Haidar; Sara Santos-Vidal; Sakunthala Kudahetti; Caroline M Moore; Alistair D R Grey; Daniel M Berney; Anju Sahdev; Paul J Cathcart; R Timothy D Oliver; Prabhakar Rajan; Jack Cuzick; Jack Cuzick; Sanjeev Madaan; Jhumur Pati; Abdul M Chowdhury; Brian R P Birch; Timothy J Dudderidge; Caroline M Moore; Alistair D R Grey; Gregory L Shaw; Kieran P Jefferson; Howard G Kynaston; Prabhakar Rajan; James S A Green; Paul J Cathcart; Daniel M Berney; Thomas Powles; R Timothy D Oliver; Anju Sahdev; Roseann Kealy; Victoria Kemp; Panos Alexandris; Kier Finnegan; Kimberly Chu Journal: BJUI Compass Date: 2022-06-11
Authors: Sanjeev Kaul; Kirk J Wojno; Steven Stone; Brent Evans; Ryan Bernhisel; Stephanie Meek; Richard E D'Anna; Jeffrey Ferguson; Jeffrey Glaser; Todd M Morgan; Jeremy Lieb; Robert Yan; Todd Cohen; Behfar Ehdaie Journal: Per Med Date: 2019-09-04 Impact factor: 2.512
Authors: Jack M Cuzick; Steven Stone; Lauren Lenz; Darl D Flake; Saradha Rajamani; Henrik Moller; Daniel Maurice Berney; Todd Cohen; Peter T Scardino Journal: Cancer Rep (Hoboken) Date: 2021-08-22
Authors: Belén Pastor-Navarro; José Rubio-Briones; Ángel Borque-Fernando; Luis M Esteban; Jose Luis Dominguez-Escrig; José Antonio López-Guerrero Journal: Int J Mol Sci Date: 2021-06-10 Impact factor: 5.923