Magnetic Resonance Imaging-based Prostate Cancer Screening in Carriers of Pathogenic Germline Mutations: Interim Results from the Initial Screening Round of the Prostate Cancer Genetic Risk Evaluation and Screening Study

Andrew E Amini; Alexandra E Hunter; Aya Almashad; Aileen J Feng; Neel D Patel; Margaret R O'Dea; Shelley R McCormick; Linda H Rodgers; Keyan Salari

doi:10.1016/j.euo.2024.01.015

Magnetic Resonance Imaging-based Prostate Cancer Screening in Carriers of Pathogenic Germline Mutations: Interim Results from the Initial Screening Round of the Prostate Cancer Genetic Risk Evaluation and Screening Study

Eur Urol Oncol. 2024 Mar 6:S2588-9311(24)00041-5. doi: 10.1016/j.euo.2024.01.015. Online ahead of print.

Authors

Andrew E Amini¹, Alexandra E Hunter¹, Aya Almashad¹, Aileen J Feng¹, Neel D Patel¹, Margaret R O'Dea¹, Shelley R McCormick², Linda H Rodgers², Keyan Salari³

Affiliations

¹ Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
² Center for Cancer Risk Assessment, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
³ Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Cancer Risk Assessment, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: ksalari@mgh.harvard.edu.

PMID: 38453598
DOI: 10.1016/j.euo.2024.01.015

Abstract

Background: The risk of early-onset and clinically aggressive prostate cancer is elevated in carriers of certain rare pathogenic germline mutations. The utility of augmenting traditional prostate-specific antigen (PSA)-based screening measures with multiparametric magnetic resonance imaging (MRI) in this population is not yet known.

Objective: To evaluate MRI-based screening in comparison with traditional PSA-based screening among individuals at an elevated genetic risk for prostate cancer.

Design, setting, and participants: Male germline carriers of pathogenic/likely pathogenic variants in any of 19 prostate cancer risk genes between the ages of 35 and 74 yr with no prior history of prostate cancer were recruited. Intervention Enrolled participants underwent screening with annual PSA, digital rectal examination (DRE), and triennial multiparametric 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, and >3.0 ng/ml for 55-74 yr), or suspicious multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3 lesion) were offered prostate biopsy. Outcome measurements and statistical analysis Endpoints were diagnosis of any and clinically significant prostate cancer, and alternative screening strategies were compared by a decision curve analysis.

Results and limitations: To date, 101 males have completed the first round of screening. The greatest proportion of participants are carriers of BRCA2 (n = 44), BRCA1 (n = 35), and ATM (n = 7) variants. Twenty-one have undergone biopsy, resulting in the detection of nine cases of cancer (seven clinically significant). For the detection of clinically significant prostate cancer, abnormal MRI (PI-RADS ≥3) demonstrated 100% sensitivity (7/7) with a negative predictive value (NPV) of 100%, whereas PSA-based screening alone had 57% (4/7) sensitivity with an NPV of 73%. Of six screening strategies evaluated in the decision curve analysis, MRI-based screening alone achieved superior net benefit at all threshold probabilities compared with PSA screening-detecting one additional cancer case per 7.5 patients, while avoiding more unnecessary biopsies at the same threshold probability.

Conclusions: Disease prevalence is high among carriers of prostate cancer-associated pathogenic germline mutations. Early results suggest that MRI-based screening enhances early detection of clinically significant disease beyond PSA screening alone.

Patient summary: In this study, we present the interim results from the PROGRESS prostate cancer screening trial. We found that in certain germline carriers of prostate cancer risk mutations, magnetic resonance imaging-based screening enhances detection of prostate cancer while reducing biopsies triggered, in comparison with traditional prostate-specific antigen screening strategies.

Keywords: Germline pathogenic variant; Multiparametric magnetic resonance imaging; Prostate cancer.