TY - JOUR
T1 - Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort
AU - Cooperberg, Matthew R.
AU - Simko, Jeffry P.
AU - Cowan, Janet E.
AU - Reid, Julia E.
AU - Djalilvand, Azita
AU - Bhatnagar, Satish
AU - Gutin, Alexander
AU - Lanchbury, Jerry S.
AU - Swanson, Gregory P.
AU - Stone, Steven
AU - Carroll, Peter R.
PY - 2013/4/10
Y1 - 2013/4/10
N2 - Purpose: We aimed to validate a previously described genetic risk score, denoted the cell-cycle progression (CCP) score, in predicting contemporary radical prostatectomy (RP) outcomes. Methods: 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. Results: 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. Conclusion: 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.
AB - Purpose: We aimed to validate a previously described genetic risk score, denoted the cell-cycle progression (CCP) score, in predicting contemporary radical prostatectomy (RP) outcomes. Methods: 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. Results: 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. Conclusion: 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.
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U2 - 10.1200/JCO.2012.46.4396
DO - 10.1200/JCO.2012.46.4396
M3 - Article
C2 - 23460710
AN - SCOPUS:84876080452
VL - 31
SP - 1428
EP - 1434
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 11
ER -