Prognostic utility of the cell cycle progression (CCP) score generated from needle biopsy in men treated with prostatectomy.

Abstract

17 Background: We developed a prognostic RNA signature that is strongly associated with prostate cancer outcomes. The cell cycle progression (CCP) score has proven to have prognostic utility in predicting disease progression in various clinical settings utilizing biopsy, transurethral resection of the prostate (TURP) and post-prostatectomy specimens. Previous studies evaluating post-surgical outcomes were conducted using CCP gene expression measured in the prostatectomy specimen. Here, we demonstrate the ability of the CCP score to predict cancer progression, as measured by both biochemical recurrence (BCR) and metastatic disease after radical prostatectomy, using needle biopsy tissue. Methods: We evaluated the CCP score in three patient cohorts. These included men from the Martini Clinic (MC, N=283), the Durham VA Medical Center (DVA, N=176), and Intermountain Healthcare (IHC, N=123). The CCP score was derived from a simulated biopsy (MC) or diagnostic biopsy (DVA and IHC), and evaluated for association with BCR and metastatic disease in univariable analysis and after adjusting for other clinical information. Results: In all three cohorts, the CCP score was associated with BCR and metastatic disease. The association with BCR remained significant after adjusting for other prognostic clinical variables. In a combined analysis of all three cohorts (N=582), the CCP score was a strong predictor of BCR in both univariable (HR per Interquartile Range [IQR] = 1.68 [95% CI: 1.41, 1.99), p value<10−6]) and multivariable analyses (HR per IQR = 1.53 [95%CI: 1.28, 1.84], p value < 10−4). CCP score was the strongest predictor of metastatic disease in both univariable analysis (HR per IQR = 6.32 [95% CI: 3.41, 11.71, p value<10−7]), and after adjusting for clinical variables (HR per IQR = 4.83 [95% CI: 2.40, 9.74, p value<10−5]). Conclusions: The CCP score derived from a needle biopsy sample was strongly associated with adverse outcome after surgery. It was the strongest predictor of eventual metastatic disease of the tested variables including Gleason and PSA. These results indicate that the CCP score can be used at disease diagnosis to better define patient prognosis and appropriate clinical care.