Patient NCCN risk classification based on combined clinical cell cycle risk (CCR) score.

Abstract

249 Background: Improved prognostic tools for newly diagnosed prostate cancer are needed to more appropriately match treatment to a patient’s risk of progression. The cell cycle progression (CCP) score is a highly validated prognostic RNA expression signature which has been combined with CAPRA (CCR, combined clinical cell cycle risk score) to generate an estimate of prostate cancer mortality (PCM) within 10-years of diagnosis. Here, we evaluate how the prognostic information from CCR can reclassify patients compared to their initial assignment to an NCCN risk category based on clinicopathologic features alone. Methods: 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). A risk reclassification scheme was applied to patients tested by the Myriad Genetics commercial laboratory (N = 16,442). First, PCM risk was assigned based on the patient’s CCR score. Next, patients whose PCM risks were outside the interquartile range (IQR) of their NCCN risk category were reclassified according to whether their PCM risks fell within the IQR of another NCCN risk category. Finally, patients whose PCM risks were below (or above) the IQR of the NCCN low (or high) category were reclassified as low (or high). Results: Based on clinicopathologic features alone the commercial cohort was classified according to NCCN Guidelines as low (N = 8,695), favorable intermediate (N = 3,347), intermediate (N = 3,086), or high risk (N = 1,224). After calculating patient risk of PCM based on CCR, 25% of the NCCN low risk men were reclassified to favorable intermediate or intermediate risk; 47% of the NCCN favorable intermediate risk men were reclassified (24% lower and 23% higher); 49% of the NCCN intermediate risk men were reclassified (24% lower and 25% higher); and 25% of the NCCN high risk were reclassified to favorable intermediate or intermediate risk. There is no outcome data associated with commercial samples. Conclusions: The prognostic information in the CCR score results in significant amounts of risk reclassification for all patients with localized disease when compared to stratification based only on NCCN risk categories.