Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort

BACKGROUND: The natural history of prostate cancer is highly variable and it is difficult to predict. We showed previously that a cell cycle progression (CCP) score was a robust predictor of outcome in a conservatively managed cohort diagnosed by transurethral resection of the prostate. A greater need is to predict outcome in patients diagnosed by needle biopsy. METHODS: Total RNA was extracted from paraffin specimens. A CCP score was calculated from expression levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason score, baseline prostate-specific antigen level, age, clinical stage, and extent of disease. The primary endpoint was death from prostate cancer. RESULTS: In univariate analysis (n = 349), the hazard ratio (HR) for death from prostate cancer was 2.02 (95% CI (1.62, 2.53), P<10(-9)) for a one-unit increase in CCP score. The CCP score was only weakly correlated with standard prognostic factors and in a multivariate analysis, CCP score dominated (HR for one-unit increase = 1.65, 95% CI (1.31, 2.09), P = 3 x 10(-5)), with Gleason score (P = 5 x 10(-4)) and prostate-specific antigen (PSA) (P = 0.017) providing significant additional contributions. CONCLUSION: For conservatively managed patients, the CCP score is the strongest independent predictor of cancer death outcome yet described and may prove valuable in managing clinically localised prostate cancer. British Journal of Cancer (2012) 106, 1095-1099. doi:10.1038/bjc.2012.39 www.bjcancer.com Published online 23 February 2012 (C) 2012 Cancer Research UK