Back to 2025 Abstracts
Multiparametric MRI screening for individuals at high risk of prostate cancer in the Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)
Aileen J. Feng, BA, Andrew E. Amini, MD, Himanshu Patankar, BS, Margaret R. O'Dea, CNP, Shelley R. McCormick, LCGC, Linda H. Rodgers-Fouche, LCGC, Keyan Salari, MD, PhD.
Massachusetts General Hospital, Boston, MA, USA.
BACKGROUND: The risk of early-onset and aggressive prostate cancer (PCa) is elevated among individuals with certain germline rare pathogenic mutations (e.g.,
BRCA2), strong family history, and Black/African ancestry. The utility of augmenting traditional PSA-based screening with multiparametric MRI in these populations is unknown. PROGRESS is an ongoing prospective early detection study evaluating MRI-based screening for individuals at high risk for PCa (NCT05129605).
METHODS: High-risk individuals are defined as:
Cohort A) germline carriers of pathogenic/likely-pathogenic variants in any of 19 risk genes; B) strong family history of PCa and negative germline genetic testing; or C) self-identified Black race. Individuals aged 35-74 are screened with annual PSA, DRE and triennial prostate MRI. Individuals with abnormal DRE, elevated age-adjusted PSA (>1.5 ng/mL for 35-49 yr, >2.0 ng/mL for 50-54 yr, >3.0 ng/mL for 55-74 yr), or suspicious MRI (PI-RADS ≥3 lesion) are offered prostate biopsy. Germline DNA was sequenced to compute a 451-variant PCa polygenic risk score (PRS). Screening strategies were compared by decision curve analysis.
RESULTS: To date, 202 men have completed the first round of screening. In Cohort A, 38 participants have undergone biopsy, detecting 16 cancers (12 clinically significant). For detection of clinically significant PCa, abnormal MRI (PI-RADS ≥4) had a sensitivity of 83% with a PPV of 56%, whereas elevated age-adjusted PSA had a sensitivity of 58% with a PPV of 39%. In decision curve analysis, MRI-based screening achieved superior net benefit compared to age-adjusted PSA or conventional PSA (>4.0 ng/mL) thresholds, with further benefit gained by refining genetic risk assessment using PRS.
CONCLUSIONS: Screening pathogenic variant carriers using MRI and age-adjusted PSA improves detection rate of clinically significant PCa compared to conventional PSA screening, which would have missed >50% of these cases. Ongoing enrollment and follow up will help further improve early detection strategies for high-risk individuals.
Back to 2025 Abstracts
