The authors used a retrospective, multi-institutional cohort of men with National Comprehensive Cancer Center (NCCN) intermediate- or high-risk localized disease (n = 741) who received single radiation therapy (RT) or multimodality therapy (ADT with RT). To be included patients must have received dose-escalated radiotherapy (at least 75.6 Gy) using external beam approaches including 3-D conformal, intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), or dichloroacetate (DCA) techniques. Among these patients, the authors examined the combined clinical cell-cycle risk (CCR) score, a validated model that combines the cell cycle progression score (CCP) with the University of California San Francisco (UCSF) Cancer of the Prostate Risk Assessment score (CAPRA).
The CCR score and a CCR-based multimodality threshold score (2.112) were evaluated using Kaplan-Meier methods and Cox regression methods.
Patients were almost exactly balanced between those above and below the CCPR risk threshold. Patients were characterized as having “sufficient” ADT if they received any or no ADT for favorable-risk disease, at least 4 months for unfavorable intermediate-risk disease, and at least 18 months for high or very high-risk disease. Forty-four percent of included patients received ADT that was deemed “insufficient”.
Over a median follow-up of 5.9 years, CCR was strongly predictive of the development of metastasis (hazard ratio [HR] 2.21, 95% confidence interval [CI] 1.70-2.87, p < 0.001).
Notably, the CCR score provided better prognostication of metastasis (C-index 0.78) than either the National Comprehensive Cancer Network (NCCN)-risk group (C-index 0.70), CAPRA score (C-index 0.71), or CCP score (C-index 0.69) alone. Utilizing bivariate analyses, the authors found that the CCR score remained highly prognostic for metastasis when accounting for ADT use in either a binary fashion (any ADT vs. none; HR 2.19, 95% CI 1.62 to 2.97, p < 0.001), ADT duration as a continuous variable (HR 2.05, 95% CI 1.54-2.72, p < 0.001), or ADT use given as less than or at the recommended duration for each NCCN risk group (HR 2.22, 95% CI 1.71-2.88, p < 0.001).
Ten-year risks of metastasis for men with CCR scores either below or above the threshold (2.112) were 4.2% and 25.3%, respectively. Notably, for men with CCR scores below the threshold, the 10-year risk of metastasis was similar for patients receiving RT alone versus RT + ADT at 4.2% and 3.9%, respectively.
Interestingly, for men with a low risk of metastasis by CCR score, NCCN risk categories do not appear to be prognostic of metastasis risk suggesting that CCR may usurp risk stratification for prognostication, independent of ADT utilization.
While there is a relative benefit to the addition of ADT to RT that has been demonstrated in many cooperative group studies, Dr. Tward emphasized that the absolute benefit of such an approach depends on the underlying risk of metastasis in the population.
The authors, therefore, concluded that the CCR score is an accurate predictor of metastasis in men undergoing dose-escalated RT, with or without ADT, adding clinically actionable information beyond that available from other risk stratification approaches. Further, use of the CCR score may allow for treatment de-intensification for patients with low scores without compromising oncologic control.
Presented by: David Tward, MD, PhD, Professor, Department of Radiation Oncology, University of Utah, Leader, Genitourinary Cancers Disease Team, Huntsman Cancer Institute, Salt Lake City, Utah
Written by: Christopher J.D. Wallis, MD, PhD, Urologic Oncology Fellow, Vanderbilt University Medical Center, Nashville, Tennessee, Twitter: @WallisCJD during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021