Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort.

Matthew R Cooperberg, Jeffry P Simko, Janet E Cowan, Julia E Reid, Azita Djalilvand, Satish Bhatnagar, Alexander Gutin, Jerry S Lanchbury, Gregory P Swanson, Steven Stone, Peter R Carroll

University of California, San Francisco, Box 1695, 1600 Divisadero St, A-624, San Francisco, CA 94143-1695, USA. mcooperberg@urology.ucsf.edu

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2013 Apr 10

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We aimed to validate a previously described genetic risk score, denoted the cell-cycle progression (CCP) score, in predicting contemporary radical prostatectomy (RP) outcomes. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. Recurrence was defined as two prostate-specific antigen levels ≥ 0.2 ng/mL or any salvage treatment. Associations between CCP score and recurrence were examined, with adjustment for clinical and pathologic variables using Cox proportional hazards regression and partial likelihood ratio tests. The CCP score was assessed for independent prognostic utility beyond a standard postoperative risk assessment (Cancer of the Prostate Risk Assessment post-Surgical [CAPRA-S] score), and a score combining CAPRA-S and CCP was validated. Eighty-two (19.9%) of 413 men experienced recurrence. The hazard ratio (HR) for each unit increase in CCP score (range, -1.62 to 2.16) was 2.1 (95% CI, 1.6 to 2.9); with adjustment for CAPRA-S, the HR was 1.7 (95% CI, 1.3 to 2.4). The score was able to substratify patients with low clinical risk as defined by CAPRA-S ≤ 2 (HR, 2.3; 95% CI, 1.4 to 3.7). Combining the CCP and CAPRA-S improved the concordance index for both the overall cohort and low-risk subset; the combined CAPRA-S + CCP score consistently predicted outcomes across the range of clinical risk. This combined score outperformed both individual scores on decision curve analysis. The CCP score was validated to have significant prognostic accuracy after controlling for all available clinical and pathologic data. The score may improve accuracy of risk stratification for men with clinically localized prostate cancer, including those with low-risk disease.

Citation

Matthew R Cooperberg, Jeffry P Simko, Janet E Cowan, Julia E Reid, Azita Djalilvand, Satish Bhatnagar, Alexander Gutin, Jerry S Lanchbury, Gregory P Swanson, Steven Stone, Peter R Carroll. Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013 Apr 10;31(11):1428-34