Abstract
The identification of biomarkers of biochemical recurrence (BCR) in prostate cancer (PCa) patients undergoing radiotherapy (RT) represents an unanswered clinical issue. The primary aim of this study was the definition of new genetic prognostic biomarkers in DNA repair genes (DRGs), considering both BCR and overall survival (OS) as clinical end-points. The secondary aim was to explore the potential clinical impact of these genetic variants with the decision curve analysis (DCA) and the sensitivity analysis.We analyzed 22 germline polymorphisms in 14 DRGs on 542 Caucasian PCa patients treated with RT as primary therapy. Significant associations were further tested with a bootstrapping technique. According to our analyses, ERCC2-rs1799793 and EXO1-rs4149963 were significantly associated with BCR (p = 0.01 and p = 0.01, respectively). Moreover, MSH6-rs3136228 was associated with a worse OS (p = 0.04). Nonetheless, the DCA and the sensitivity analyses gave no ultimate response about the clinical impact of such variants.This study highlights the potential prognostic role of polymorphisms in DRGs for PCa, paving the way to the introduction of not invasive tools for the personalization of patients management. Nonetheless, other prospective studies are necessary to ultimately clarify the clinical impact of pharmacogenetics in PCa.
Highlights
The clinical course of prostate cancer (PCa) patients is difficult to predict since men with similar tumour features can experience strikingly different outcomes
More in detail, according to European guidelines, biochemical recurrence (BCR) has been defined with an increase of serum PSA levels more than 2 ng/mL above the lowest level reached after the end of RT
The clinical value of these new biomarkers have been explored with decision curve analysis (DCA) and sensitivity analysis, even if no ultimate response has been obtained
Summary
The clinical course of prostate cancer (PCa) patients is difficult to predict since men with similar tumour features can experience strikingly different outcomes. The prompt identification of this subgroup of patients can play a pivotal clinical role because it can be translated in a more frequent patients’ follow-up and a more appropriate maintenance therapy. Like PSA, Gleason score, and TNM stage, are currently used to predict outcome following RT for localized PCa. the need of more specific and accurate prognostic biomarkers has not been yet overcome [4]. Several analyses have been conducted until now to determine the potential clinical role of polymorphisms in DNA repair genes (DRGs) in patients undergoing RT [7,8,9,10,11,12,13]. The potential clinical impact of introducing genetic analysis is not still clear
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