The 'Prostate Cancer Screening for People at Genetic Risk of Aggressive Disease' (PATROL) study.

Abstract

BACKGROUND: Inherited (germline) pathogenic and likely pathogenic variants (gPVs) in key genes associated with increased risk of prostate cancer (PCa) now warrant more attentive PCa screening per National Comprehensive Cancer Network (NCCN) guidelines-e.g., BRCA2, HOXB13, ATM, BRCA1, MSH2, MSH6, CHEK2 and TP53. However, the optimal early detection strategy for gPV carriers, including use of age-adjusted PSA thresholds and prostate imaging may be refined. and as a means to investigate novel biomarkers. STUDY DESIGN: 'Prostate Cancer Screening for People at Genetic Risk of Aggressive Disease' (PATROL) is a multicentre, prospective early detection study for individuals at increased risk for PCa due to carrying a gPV in a PCa risk gene. ENDPOINTS: The primary endpoint is to determine the positive predictive value of pre-defined age-directed prostate-specific antigen (PSA) level thresholds and prostate-specific imaging, e.g., multiparametric magnetic resonance imaging (MRI) for clinically significant PCa on biopsy for individuals at risk of PCa due to a gPV. Exploratory endpoints include characterising clinicopathological characteristics of PCa and patient-reported outcomes. Biospecimens will be collected to evaluate emerging clinical and research biomarkers. PATIENTS AND METHODS: Key eligibility includes: individuals aged &#x2265;40&#x2009;years who carry a gPV in an eligible gene, who have no prior diagnosis of PCa, do not have another active malignancy, and provide informed consent. Study procedures include annual physical examination and PSA. Imaging with MRI is optional at baseline and recommended if the PSA level is above the protocol-recommended PSA level threshold. Participants will be offered prostate biopsy for any clinical concern, PSA level >1.0&#x2009;ng/mL if aged <50&#x2009;years; PSA level >1.5&#x2009;ng/mL if aged 50-59&#x2009;years; PSA level >2.0&#x2009;ng/mL if aged &#x2265;60&#x2009;years. If PCa is diagnosed, clinical care is determined by the participant and treating physician. If opting for active surveillance, study procedures will be collected annually for 10&#x2009;years or until definitive treatment. If definitive treatment, study procedures will be collected for an additional 1&#x2009;year. Long-term clinical outcomes will be collected annually until the study closes.