Impact of prostate cancer screening in European ancestry un-affected men with germline DNA repair pathogenic variants

Prostate cancer (PCa) is a significant global health concern, ranking as the second most prevalent cancer among men worldwide. Genetic factors, particularly germline pathogenic variants (PVs) in DNA repair genes (DRGs), play a crucial role in PCa predisposition. Our study aimed to assess patients' adherence to a targeted PCa screening program targeting high-risk individuals with DRG PVs and evaluate the potential reduction in biopsy and MRI rates by employing our screening protocol.

We conducted a prospective ongoing trial evaluating targeted PCa screening in men with documented PVs in DRGs. Screening involved annual assessment of medical history, physical examination, prostate-specific antigen (PSA) testing, Prostate Health Index (PHI), and multiparametric magnetic resonance imaging (mpMRI) when indicated. Descriptive statistics were used to analyse patient characteristics, and adherence to screening was evaluated at three time points: baseline (T0), one year (T1), and two years (T2) from enrolment.

A total of 101 high-risk individuals were enrolled, with a median age of 52 years. Adherence to screening was high, with 72.3% of patients attending the first annual follow-up (T1) and 100% attending the second follow-up (T2). Despite elevated PSA levels in some patients, no PCa was detected during the study period. However, our screening protocol demonstrated the potential in reducing unnecessary biopsies and MRIs, particularly in patients with elevated PSA but low PHI values. Limitations include the ongoing nature of the study, small sample size, and lack of non-carrier controls.

Our findings described a new PCa screening strategy integrated with genetic risk factors. The incorporation of PHI shows promise in improving the efficiency of diagnostic procedures while minimizing unnecessary interventions. High adherence among high-risk individuals underscores the potential effectiveness of targeted screening programs.