Development and validation of a novel integrated clinical-genomic risk group classification for localized prostate cancer

Daniel E. Spratt, Jingbin Zhang, Maria Santiago-Jiḿenez, Robert T. Dess, John W. Davis, Robert B. Den, Adam P. Dicker, Christopher J. Kane, Alan Pollack, Radka Stoyanova, Firas Abdollah, Ashley E. Ross, Adam Cole, Edward Uchio, Josh M. Randall, Hao Nguyen, Shuang G. Zhao, Rohit Mehra, Andrew G. Glass, Lucia L.C. LamJijumon Chelliserry, Marguerite Du Plessis, Voleak Choeurng, Maria Aranes, Tyler Kolisnik, Jennifer Margrave, Jason Alter, Jennifer Jordan, Christine Buerki, Kasra Yousefi, Zaid Haddad, Elai Davicioni, Edouard J. Trabulsi, Stacy Loeb, Ashutosh Tewari, Peter R. Carroll, Sheila Weinmann, Edward M. Schaeffer, Eric A. Klein, R. Jeffrey Karnes, Felix Y. Feng, Paul L. Nguyen

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorableintermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the threetier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95%CI, 0.65 to 0.84), and 30%of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk formetastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

Original languageEnglish
Pages (from-to)581-590
Number of pages10
JournalJournal of Clinical Oncology
Issue number6
StatePublished - 20 Feb 2018


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