Genetic and clinical profiles of early-onset prostate cancer in Puerto Rican men: A preliminary characterization

Background: Prostate cancer (PCA) is the second leading cause of cancer-related death among men in the US. Early-onset prostate cancer (EOPCa) accounts for ~10% of all PCA diagnoses, with an ~58,694 new cases reported worldwide in 2021. Although EOPCa accounts for a growing proportion of cases, it remains underexplored. Younger patients often present with distinct clinical features, hereditary predispositions, and long-term survivorship challenges. Hispanic/Latino men, particularly those from Puerto Rico, experience disparities in incidence and outcomes, yet remain underrepresented in PCA research. A better understanding of the epidemiological, clinical, and germline genetic profile of Puerto Rican men with EOPCa is essential to guide risk stratification and inform precision medicine strategies. Methods: This study retrospectively identified 80 cases of EOPCa of 9,393 patients treated for PCA between 2020-2025 in a tertiary hospital in southern PR. Demographic, clinicopathological variables were collected, including age, PSA, BMI, Gleason score (GS), tumor stage, family history, lifestyle factors, and treatments. Germline genetic testing results were analyzed and variants classified as pathogenic, variants of uncertain significance (VUS), or benign. Frequencies of recurrent alterations were calculated. Results: Eighty patients were identified; 39 met the inclusion criteria. Age ranged 37-49 years (mean 45.7). PSA at diagnosis ranged 1.7-25.4 ng/mL (mean 6.2). Nearly half (48.7%) were obese (BMI ≥30). At biopsy, GS 6 was most frequent (56.4%); following prostatectomy (87.2% of cases), GS 6 remained most common (50.0%), followed by GS 8 (23.5%). Stage T2 (55.9%) and T3 (23.5%) predominated. Family history of PCA was reported by 38.0%. Most patients consumed alcohol (76.9%) but denied smoking (71.8%). Germline testing identified 10.3% pathogenic variants, 35.9% VUS, and 5.1% carriers, with the remainder negative. In total, 21 alterations were detected: 15 VUS, 5 pathogenic, and 1 benign. Alterations were distributed across 15 genes, with recurrent findings in RECQL4 (n=3), POLD1 (n=3), ATM (n=2), and TMEM127 (n=2). Conclusions: This study provides the first characterization of the epidemiological, clinical, and germline genetic profile of EOPCa in Puerto Rico. Findings highlight a notable burden of germline alterations and underscore the importance of incorporating genetic testing into clinical management. Expanding research among underrepresented populations is critical to guide early detection, refine prognostication, and reduce PCA disparities.