A novel comprehensive cancer genome profiling for non-metastatic prostate cancer: study protocol with FPG500 to detect actionable alterations representative of progressive disease

Background and Objective: Prostate cancer (PCa) presents with substantial biological heterogeneity and variable clinical outcomes. While genomic alterations in high-risk and locally advanced cases may signal early progression or micrometastatic disease, their clinical finding and utility remains underexplored. This study aims to apply a comprehensive cancer genome profiling through next-generation sequencing (NGS) to identify actionable mutations predictive of disease progression in non-metastatic PCa. Study Design: This single-centre, prospective observational cohort study (ClinicalTrials.gov: NCT06875297) is designed to recruit patients with high-risk or locally advanced PCa undergoing radical prostatectomy (RP); a complementary arm of low-risk patients managed by either active surveillance or RP are considered as well. Participants are enrolled from the Fondazione Policlinico Universitario A. Gemelli IRCCS. Endpoints: The primary endpoint is to detect Association for Molecular Pathology (AMP)-American Society of Clinical Oncology [ASCO]-College of American Pathologists [CAP] Tier I–II genomic alterations associated with biochemical recurrence or progression in high-risk and locally advanced PCa. Secondary endpoints include genomic alterations relevant to time to radiographic progression and castration resistance; for the low-risk subset, upstage and/or upgrade are considered as actionable endpoints to be predicted through NGS. Funding and Ethics and Trial Registration: The study is non-profit, ethically approved (Lazio Area 3, identifier: 7618), and registered at ClinicalTrials.gov (NCT06875297).