Value of cell cycle progression (CCP) score to predict biochemical recurrence and definitive post-surgical pathology.

Abstract

5043 Background: Prostate cancer (PCA) has a highly variable natural history and better tools are needed to more appropriately match treatment to a patient’s risk of progression. A prognostic mRNA expression signature composed of genes involved in cell cycle progression (CCP) has been previously developed. Here, we tested the utility of this signature to predict biochemical recurrence (BCR) and definitive post-surgical pathological stage. Methods: The eligible patient population was treated for PCA by radical prostatectomy at a single high volume center (2005-2006). We randomly selected 390 patients for the study. From each patient we prepared a ‘simulated biopsy’ by removing a tissue cylinder (0.6mm) from the post-surgical FFPE block containing the largest tumor foci. 249 patients remained eligible for analysis after excluding patients for either insufficient tumor in the biopsy, poor quality molecular data, or receiving neoadjuvant therapy. The median follow-up time for patients who did not recur was 60.8 months. 46 patients experienced BCR. CCP scores were generated as in previous studies. Cox PH models and logistic regression were used to evaluate CCP associations with outcome. Results: The CCP signature was a highly significant univariate predictor of BCR (HR=2.03; 95%CI: 1.48-2.79; p=3.1x10-5). After adjusting for clinical parameters including biopsy Gleason and PSA, the hazard ratio for CCP score remained significant (HR=1.6; 95%CI: 1.15-2.24; p=0.0068). In a multivariate model including PSA, biopsy Gleason, and clinical stage, CCP score was also an independent predictor of pathological stage (pT2 vs. pT3, p=0.029). In this analysis, PSA was the most predictive variable, but CCP score and clinical stage also provided important and non-redundant information. Conclusions: The CCP score has predicted PCA outcomes in multiple patient cohorts and different clinical settings. In this study, we have extended the demonstrated clinical utility to a modern patient cohort from Europe, and for the first time, provided evidence that the score can be used to predict definitive post-surgical tumor stage. The CCP expression score is an emerging and important component in evaluating PCA prognosis.