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PATIENT RISK RECLASSIFICATION BASED ON COMBINED CLINICAL CELL CYCLE RISK (CCR) SCORE
Mitchell H. Sokoloff, MD, FACS1, Steven Stone, PhD2, Julia Reid, MStat2, E. David Crawford, MD3, Michael K. Brawer, MD4.
1University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA, USA, 2Myriad Genetics, Inc., Salt Lake City, UT, USA, 3University of Colorado, Aurora, CO, USA, 4Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.

BACKGROUND: Improved prognostic tools for newly diagnosed prostate cancer are needed to more appropriately match treatment to a patient’s risk of progression. The CCR score is a validated prognostic tool that estimates 10-year prostate cancer mortality (PCM) based on prognostic information from both molecular (cell cycle progression (CCP) gene expression) and clinical (CAPRA) variables. We evaluate how the CCR score can reclassify PCM-risk for men tested within the AUA New England (NE) section relative to NCCN and AUA risk categories.
METHODS: Prostate biopsy samples from 633 men within the AUA NE section were submitted for commercial testing. The CCR score was previously validated and is calculated as a linear combination of CAPRA and CCP score (0.39 x CAPRA + 0.57 x CCP). Patients were assigned to NCCN and AUA risk categories using clinicopathologic data obtained from test request forms. Interquartile ranges (IQR) for each NCCN/AUA risk category were determined from the full commercial cohort (N=20,958). Patients whose CCR-based PCM risks were outside the IQR of their NCCN/AUA risk category were reclassified according to whether their PCM risk fell within the IQR of another risk category.
RESULTS: Based on NCCN guidelines using clinicopathologic features alone, the commercial cohort was classified as low (n=386, 61.0%), favorable intermediate (n=113, 17.9%), intermediate (n=87, 13.7%), and high risk (n=47, 7.4%). After calculating PCM-risk based on CCR, 30.0%% of men were reclassified to a different risk category relative to NCCN criteria (9.0% lower, 21.0% higher; see Table). Similarly, men were classified as AUA low (n=386, 61.0%), intermediate (n=186, 29.4%), and high risk (n=61, 9.6%) based on clinical features. PCM-risk based on CCR scores resulted in the reclassification of 27.2% of men relative to AUA criteria (7.3% lower, 19.9% higher; see Table).
CONCLUSIONS: The prognostic information in the CCR score results in significant risk reclassification for all patients with localized disease when compared to stratification based only on clinicopathologic criteria.
Risk reclassification. Bold cells represent men whose risk was reclassified using the CCR score.
Risk Reclassification
NCCN Risk CategoryLowFavorable IntermediateIntermediateHigh
NCCN Very Low/Low (n=386)294 (76.2%)75 (19.4%)17 (4.4%)0
NCCN Favorable Intermediate (n=113)26 (23.0%)61 (54.0%)25 (22.1%)1 (0.9%)
NCCN Intermediate (n=87)2 (2.3%)23 (26.4%)47 (54.0%)15 (17.2%)
NCCN High (n=47)01 (2.1%)5 (10.6%)41 (87.2%)
Total322 (50.9%)160 (25.3%)94 (14.8%)57 (9.0%)
AUA Risk CategoryLowIntermediateHigh
AUA Low (n=386)308 (79.8%)73 (18.9%)5 (1.3%)
AUA Intermediate (n=186)34 (18.3%)104 (55.9%)48 (25.8%)
AUA High (n=61)4 (6.6%)8 (13.1%)49 (80.3%)
Total346 (54.7%)185 (29.2%)102 (16.1%)


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