A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS.
The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort.
In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10-5). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively).
The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS.
Urologic oncology. 2018 Apr 11 [Epub ahead of print]
Daniel W Lin, E David Crawford, Thomas Keane, Brent Evans, Julia Reid, Saradha Rajamani, Krystal Brown, Alexander Gutin, Jonathan Tward, Peter Scardino, Michael Brawer, Steven Stone, Jack Cuzick
University of Washington, Seattle, WA. Electronic address: ., University of Colorado, Denver, CO., Medical University of South Carolina, Charleston, SC., Myriad Genetics, Inc, Salt Lake City, UT., University of Utah Huntsman Cancer Hospital, Salt Lake City, UT., Memorial Sloan-Kettering Cancer Center, New York City, NY., Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.