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.
To evaluate MRI-based screening in comparison with traditional PSA-based screening among individuals at an elevated genetic risk for prostate cancer.
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.
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.
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.
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.
European urology oncology. 2024 Mar 06 [Epub ahead of print]
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
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., 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: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/38453598