The clinical cell-cycle risk (CCR) score is associated with metastasis after radiation therapy and provides guidance on when to forgo combined androgen deprivation therapy with dose-escalated radiation.

PURPOSE The clinical cell-cycle risk (CCR) score, which combines the University of California San Francisco Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). METHODS This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N=741). Patients were treated with dose-escalated RT ± ADT. The primary outcome was time to metastasis. RESULTS CCR score prognosticated metastasis [hazard ratio per unit score (HR) 2.22, 95% confidence interval (CI) 1.71-2.89, p<0.001]. CCR score better prognosticated metastasis than NCCN risk group (CCR p <0.001; NCCN p = 0.46), CAPRA score (CCR p = 0.002; CAPRA p = 0.59), or CCP score (CCR p <0.001; CCP p = 0.59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT vs. no ADT (HR 2.18, 95% CI 1.61-2.96, p<0.001), ADT duration as a continuous variable (HR 2.11, 95% CI 1.59-2.79, p<0.001), or ADT given at or below the recommended duration for each NCCN risk group (HR 2.19, 95% CI 1.69-2.86, p<0.001). Men with CCR scores below or above the multimodality threshold (CCR=2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 3.7% 10-year risk of metastasis whereas for men receiving RT plus ADT, 10-year risk of metastasis was 3.7%. CONCLUSIONS CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT ±ADT. Men with scores below the multimodality threshold may not significantly reduce their 10-year risk of metastasis by adding ADT.