Initial biopsy results of the PATROL study: Prostate screening for people with inherited risk of developing aggressive prostate cancer.

426 Background: Germline pathogenic variants (gPV) in prostate cancer (PrCa) risk genes are associated with aggressive disease and worse outcomes. However, the degree of risk by gene, the optimal PSA thresholds for biopsy, and the utility of MRI for screening are not well characterized. Therefore, we developed the PATROL study (clinicaltrials.gov: NCT04472338), a prospective multi-center early detection study for people at risk for PrCa due to variants in PrCa risk genes. Here, we report initial biopsy results of participants enrolled to date. Methods: The primary endpoint of PATROL is to determine the positive predictive value of predefined age-adjusted PSA thresholds and prostate-specific imaging for biopsy. Key eligibility criteria include: people ≥40y with prostates that carry a gPV in one or more of 13 PrCa risk genes. Participants undergo prostate biopsy per age-adjusted PSA threshold recommendations: PSA >1.0 ng/mL if <50y; PSA >1.5 ng/mL if 50-59y; PSA >2.0 ng/mL if ≥60y). Patients are encouraged to receive a prostate MRI at baseline and/or within one year of biopsy. Clinically significant prostate cancer (csPrCa) was defined as ≥Grade Group 2 (GG2). Results: Of 291 patients enrolled in PATROL at the time of this analysis, gPVs were most frequent in BRCA2 (n=141, 48%) and BRCA1 (n=71, 24%). 55 patients have undergone biopsy, with a median age of 57 (IQR 52-66) and median PSA of 2.2 (IQR 1.2-4.4) at time of biopsy. Of these biopsies, 10 (18.2%) had GG1 disease, and 11 (20%) had csPrCa. Of the men with csPrCa, six (55%) had PSA above the PATROL age-adjusted threshold but less than standard-of-care 4 ng/ml. An additional three (27%) patients had abnormal MRI with normal age-adjusted PSA. All 11 men with csPrCa underwent definitive treatment, while 7 of the men (70%) with GG1 initiated active surveillance. In a logistic regression model adjusting for age, gPV and PSA level, having a PIRADS 4 or 5 lesion was associated with csPrCa (OR 34.3, p=0.001). Conclusions: Screening gPV carriers using age-adjusted PSA and MRI resulted in 20% of biopsies detecting clinically significant prostate cancer. Conventional PSA thresholds for biopsy would have missed more than 80% of the clinically significant prostate cancer in men with gPV. Ongoing enrollment, site expansion and longer-term follow-up in this study, along with other studies will help improve the early detection of significant prostate cancer among men with gPV. Clinical trial information: NCT04472338 .