Prospective prostate cancer screening in germline pathogenic variant carriers: The PATROL study.

Abstract

10505 Background: Germline pathogenic variants (gPV) in prostate cancer (PCa) risk genes are associated with aggressive disease, but optimal screening thresholds for this population are unclear. We report early results from the Prostate Cancer Screening for People at Genetic Risk for Aggressive Disease (PATROL) study. Methods: PATROL is a multicenter, prospective study enrolling participants ≥40 years with a gPV in at least one of 13 PCa risk genes. Biopsy is recommended using age-specific prostate-specific antigen (PSA) thresholds: > 1.0 ng/mL (< 50y), > 1.5 (50–59y), > 2.0 (≥60y). Prostate multiparametric MRI is encouraged at baseline and within 1 year of biopsy. Clinically significant PCa (csPCa) was defined as Grade Group (GG) ≥2 (NCT04472338). Results: As of 12/1/2025, 436 participants were enrolled; 69% carried BRCA1/2 gPVs ( BRCA2 46%, BRCA1 22%), 12% carried mismatch repair gene variants, and gPVs in other genes were each ≤7%. Overall, 106 participants underwent 119 on-study biopsies (median age 61 [IQR 53–68]) with a median PSA 2.3 ng/mL [IQR 1.3–3.9]). GG1 disease was detected in 21/119 (18%) biopsies and csPCa in 21/119 (18%) biopsies. Among csPCa, the median PSA was 3.2 ng/mL (IQR 2.2-4.1), and 76% (16/21) had a PIRADS 4-5 lesion. Fifteen (71%) and 14 (67%) of GG1 and csPCa, respectively, were identified in participants with BRCA1/2 gPVs. In multivariable logistic regression adjusting for age, PSA, and genetic status, PI-RADS 4-5 was associated with csPCa (OR 12.2, 95% CI 3.3-45.4). Of the 17 men with GG1 PCa, 11 (65%) elected active surveillance. Of the 11 men on surveillance, median follow up time was 19 months, with one (9%) upgraded to GG ≥2 and who underwent definitive treatment. In total, 25 participants underwent definitive treatment; 18 with initial diagnosis of csPCA, six GG1 who elected for definitive treatment and one enrollee with GG1 upgraded to GG ≥2. Of the 25 patients who elected definitive treatment, 88% (22/25) of underwent surgery, two underwent radiation, and one underwent focal therapy. Of surgery patients, there were no postoperative complications. At a median follow-up time of 16 months, all currently have undetectable PSA, and one patient required salvage radiation therapy. Conclusions: Age-specific PSA-driven biopsy in gPV carriers yielded ~20% csPCa detection, with two-thirds occurring at PSA < 4 ng/mL (common biopsy threshold). MRI (PI-RADS 4–5) strongly predicted csPCa and may improve inherited-risk screening algorithms. With limited follow-up, surveillance of low-risk PCa among gPV carriers appears to be feasible, and definitive treatment of gPV carriers found with csPCa is effective. Clinical trial information: NCT04472338 .