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

Abstract

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. 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. 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. The study is non-profit, ethically approved (Lazio Area 3, identifier: 7618), and registered at ClinicalTrials.gov (NCT06875297).