Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.

Spratt DE1, Zhang J1, Santiago-Jiménez M1, Dess RT1, Davis JW1, Den RB1, Dicker AP1, Kane CJ1, Pollack A1, Stoyanova R1, Abdollah F1, Ross AE1, Cole A1, Uchio E1, Randall JM1, Nguyen H1, Zhao SG1, Mehra R1, Glass AG1, Lam LLC1, Chelliserry J1, du Plessis M1, Choeurng V1, Aranes M1, Kolisnik T1, Margrave J1, Alter J1, Jordan J1, Buerki C1, Yousefi K1, Haddad Z1, Davicioni E1, Trabulsi EJ1, Loeb S1, Tewari A1, Carroll PR1, Weinmann S1, Schaeffer EM1, Klein EA1, Karnes RJ1, Feng FY1, Nguyen PL1.

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Abstract

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, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier 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 for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

PMID:

29185869

DOI:

10.1200/JCO.2017.74.2940