SC 236 br In this study the higher frequency
In this study, the higher frequency of PTEN loss among AA men was confirmed . However, this did not impact
risk discrimination, as PTEN SC 236 was not significant-ly associated with progression to metastatic disease. The study also showed that ancestry does not appear to impact the prognostic information provided by the CCP score, with no significant differences in HRs according to ancestry (p = 0.20). This is consistent with a previous study that showed equivalent CCP HRs in a cohort that included 81 AA men . Furthermore, the predicted risk for metastatic disease did not differ between AA and non-AA patients after accounting for all available molecular and clinicopathologic prognostic information in this study cohort (Fig. 3). These data may indicate that both the molecular score and the derived predicted risk (based on the CCR score) could be used to help in guiding appropriate clinical management of both AA and non-AA patients with newly diagnosed prostate cancer.
This study has several limitations. First, ancestry was self-reported. This may introduce error and limit the generalizability of the conclusions, as population-based genetic heterogeneity was not addressed . Although obtaining genetic information for this patient population could have provided more precise ancestry information, this was impractical within the scope of the study. Second, the study was retrospective in nature. To minimize the sample bias that can occur in retrospective studies, we studied a population-based disease cohort that was prospectively collected and molecular testing was per-formed for as many evaluable men as possible. This design conforms to best practice as defined by several peer-reviewed guidelines for biomarker validation . In addition, patients were not randomly assigned to treat-ment regimens. Although clinical information is available, factors that might have guided treatment choices remain unknown and no conclusions can be drawn about the relative efficacy of different therapies. The clinical follow-up is also somewhat limited (median 5.6 yr) and conclu-sions regarding late metastatic events require caution. Finally, the men in Enhancer study were mostly treated, and therefore the data presented add little to the evidence that the CCP score can help in selecting men for deferred treatment. However, the study expands the evidence that the test can identify men at high risk of failing on standard therapy.
Appropriate clinical management of newly diagnosed prostate cancer depends on accurate risk discrimination. This is the first study to robustly evaluate the impact of ancestry on the prognostic performance of this molecular test. The study indicates that the prognostic information provided by the CCP score is independent of ancestry and therefore could be used to improve risk discrimination among both AA and non-AA men with localized prostate cancer.
Author contributions: Daniel J. Canter had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Canter, Reid, Halat, Gurtner, Sangale, Brawer, Stone, Bardot. Acquisition of data: Canter, Latsis, Variano, Halat, Gurtner, Sangale, Brawer, Stone, Bardot.
Analysis and interpretation of data: Canter, Reid, Halat, Rajamani, Gurtner, Sangale, Brawer, Stone, Bardot. Drafting of the manuscript: Canter, Reid, Halat, Rajamani, Gurtner, Sangale, Brawer, Stone, Bardot. Critical revision of the manuscript for important intellectual content: Canter, Reid, Latsis, Variano, Halat, Rajamani, Gurtner, Sangale, Brawer, Stone, Bardot.
Statistical analysis: Reid, Rajamani.
Obtaining funding: Reid, Sangale, Brawer, Stone.