Abstract
BackgroundAccurate risk stratification can help guide appropriate treatment decisions in men with localized prostate cancer. Here, we evaluated the independent ability of the molecular cell cycle progression (CCP) score and the combined cell-cycle clinical risk (CCR) score to predict 10-year risk of progression to metastatic disease in a large, pooled analysis of men with definitively treated prostate cancer.MethodsThe pooled analysis included 1,062 patients from four institutions (Martini Clinic, Durham VA Medical Center, Intermountain Healthcare, Ochsner Clinic) treated definitively for localized prostate cancer by either radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy ± hormone therapy). The CCP score was determined using the RNA expression of 46 genes from archival formalin-fixed paraffin-embedded biopsy tissue. The CCR score was calculated using a predefined linear combination of the CCP score and the Cancer of the Prostate Risk Assessment (CAPRA) score. The scores were evaluated for association with 10-year risk of metastatic disease following definitive therapy after adjusting for other clinical variables.ResultsThe CCP score was strongly associated with 10-year risk of metastatic disease in multivariable analysis [Hazard Ratio per unit score = 2.21; 95% confidence interval (CI) 1.64, 2.98; p = 1.9 × 10−6] after adjusting for CAPRA, treatment type, and cohort. CCR was also highly prognostic (Hazard Ratio per unit score = 4.00; 95% CI 2.95, 5.42; p = 6.3 × 10−21). There was no evidence of interaction between CCP or CCR and cohort (p = 0.79 and p = 0.86, respectively) or treatment type (p = 0.55 and p = 0.78, respectively). Observed patient CCR-based predicted risks for metastatic disease by 10 years ranged from 0.1 to 99.4%, (IQR 0.7%, 4.6%).ConclusionsBoth CCP and CCR scores provided independent prognostic information for predicting progression to metastatic disease after both surgery and radiation. These results further demonstrate their potential use as a risk stratification tool in patients with newly-diagnosed prostate cancer.
Highlights
Supplementary information The online version of this article contains supplementary material, which is available to authorized users.Ochsner Clinic, Department of Urology, New Orleans, LA, USA 2 Queensland School of Medicine, Queensland, Australia 3 Cedars-Sinai Medical Center, Los Angeles, CA and Durham VAMedical Center, Durham, NC, USAThe natural history of localized prostate cancer is highly variable, which can cause uncertainty in the selection of the appropriate management strategy for the individual patient [1, 2]
Median follow-up time for patients without events was 6.05 [Interquartile Range (IQR) 4.8, 8.0] years, and overall 3.3% (35/1,062) of patients progressed to metastatic disease (Table 1)
On univariate analysis of the pooled cohort, the cycle progression (CCP) score was strongly associated with progression to metastatic disease [Hazard Ratio (HR) per unit score = 2.93, p = 1.8 × 10−11], as were Cancer of the Prostate Risk Assessment (CAPRA) score, treatment, and cohort (Table 2)
Summary
The natural history of localized prostate cancer is highly variable, which can cause uncertainty in the selection of the appropriate management strategy for the individual patient [1, 2]. To help address this uncertainty, prognostic molecular. Accurate risk stratification can help guide appropriate treatment decisions in men with localized prostate cancer. We evaluated the independent ability of the molecular cell cycle progression (CCP) score and the combined cell-cycle clinical risk (CCR) score to predict 10-year risk of progression to metastatic disease in a large, pooled analysis of men with definitively treated prostate cancer
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