INTENSIFIED MRI-BASED PROSTATE CANCER SCREENING IN GERMLINE CARRIERS OF RARE PATHOGENIC VARIANTS: INTERIM RESULTS FROM THE INITIAL SCREENING ROUND OF THE PROGRESS STUDY.

The risk of early-onset and clinically aggressive prostate cancer is elevated in carriers of certain rare pathogenic germline variants.;;The utility of augmenting traditional PSA-based screening measures with multiparametric MRI imaging in this population is not yet known. The Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS) seeks to evaluate an intensified screening program that incorporates prostate MRI-based screening for early detection of prostate cancer among individuals at elevated genetic risk. Male carriers of pathogenic/likely-pathogenic germline variants in 19 prostate cancer risk genes between the ages of 35-75 are eligible for participation. Enrolled participants undergo a screening protocol consisting of annual PSA and DRE and triennial multiparametric MRI. Triggers for recommending prostate biopsy include elevated PSA, abnormal DRE or suspicious MRI (PI-RADS ≥3). PSA is considered elevated based on age-adjusted cutoffs of >1.5 ng/mL for 35-49 years of age, >2.0 ng/mL for 50-54 years of age, and >3.0 ng/ml for 55-70 years of age. Decision curve analysis was performed to compare the relative benefit of three screening strategies for the detection of clinically significant prostate cancer: 1) elevated PSA alone, 2) abnormal MRI alone and 3) elevated PSA followed by abnormal MRI. 101 men have completed the first round of screening. The greatest proportion are carriers of;BRCA2;(n = 44),;BRCA1;(n= 35), and;ATM;(n = 7) variants. Thirteen had elevated age-adjusted PSA, 2 had abnormal DRE, and 17 had abnormal MRIs. Twenty have undergone biopsy, detecting 9 cancers (7 clinically significant). MRI was the sole indication for 11 of 20 biopsies and detected all biopsy-diagnosed prostate cancers. PSA-based screening alone would have detected 4 cancers (44%) but missed 5, including three clinically significant cases. Of the three screening strategies, MRI-based screening alone or with PSA-triage were superior in decision curve analysis. MRI screening alone was equivalent to a strategy that detects ∼1 cancer per 5 patients without any unnecessary biopsies (compared to conducting no biopsies, threshold probability, 15%). Net reduction in biopsies was greatest using strategies of biopsy triggered by MRI alone and PSA-triaged MRI, across all threshold probabilities. Disease prevalence is high among carriers of prostate cancer-associated pathogenic germline variants. Early results suggest MRI-based screening alone or in conjunction with PSA screening enhances early detection of clinically significant disease. [ABSTRACT FROM AUTHOR]