Meta-Analysis of the Prognostic Utility of the Cell Cycle Progression Score Generated from Needle Biopsy in Men Treated with Definitive Therapy
The cell cycle progression (CCP) score is a validated prognostic molecular RNA signature that has proven to have utility in various clinical settings. Here, we evaluated the ability of the score to predict 10-year risk of metastatic disease in a large meta-analysis of patients who received definitive therapy.
We combined patient cohorts from the Martini Clinic, Durham VA Medical Center, Intermountain Healthcare, and Ochsner Clinic (N = 1,062). Men were included if they were treated for localized prostate cancer by either radical prostatectomy (RP) or external beam radiotherapy (EBRT). The CCP score was derived from biopsy and evaluated for association with 10-year risk of metastatic disease following definitive therapy after adjusting for other clinical information. We also evaluated the performance of a clinical cell-cycle risk (CCR) score [CCR = (0.57 x CCP) + (0.39 x cancer of the prostate risk assessment (CAPRA) score)] for predicting metastatic disease and derived a CCR-based metastatic risk curve. Patient data was censored at 10 years.
In the combined cohort, 3.3% (35/1062) of the patients progressed to metastatic disease by 10 years. The CCP score was strongly associated with 10-year risk of metastatic disease in multivariable analysis (Hazard Ratio (HR) per unit score = 2.14, 95% Confidence Interval (CI) 1.58, 2.86; p=3.1x10-6) after adjusting for CAPRA, ethnicity, and treatment. Cohort was not significant (p=0.71) nor was there evidence for an interaction between CCP and the four cohorts (p=0.69). CCR was also highly prognostic in a univariate model (HR per unit score = 4.00, 95% CI 2.97, 5.47; p=6.3x10-21). There was no evidence of interaction between CCR and cohort (p=0.86). Observed patient CCR-based predicted risks for metastatic disease by 10 years ranged from 0.1% to 99.4%, (IQR 0.7%, 4.6%), and the highest decile had metastatic risks greater than 14%. The C-index was 0.790 for CCP, 0.857 for CAPRA, and 0.894 for CCR. Calibration plots show that CCR was better calibrated than CAPRA, and that its prediction range was wider.
The CCP score derived from biopsy sample was strongly associated with adverse outcome after definitive therapy. These results indicate that the CCP score can be used to guide intensity of therapeutic intervention in patients who need treatment.
Funding: Myriad Genetics, Inc.