Prostate Cancer Genetic Risk Evaluation and Screening Study

Recruiting

• Conditions: BRCA2 Mutation; Prostate Cancer; ATM Gene Mutation; MMR Mutation; BRCA1 Mutation; Prostatic Neoplasm; Lynch Syndrome; Genetic Predisposition to Disease
• Interventions: Diagnostic Test: Prostate cancer screening

• Registration Number: NCT05129605
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

This study aims to define the natural history of men at high genetic risk for prostate cancer on the basis of specific germline genetic mutations, family history, or Black/African ancestry and evaluate the utility of prostate MRI as a screening tool. The hypothesis is that this targeted population of men are at elevated risk of developing prostate cancer compared to the general population, and enhanced screening with MRI will enable early detection and diagnosis of potentially aggressive prostate cancer, characterization of the penetrance of specific mutations, and potentially identify new genetic risk mutations.

Detailed Description

Prostate cancer is the most common malignancy and the second leading cause of cancer-related deaths in American men. Prostate cancer has substantial inherited predisposition and men harboring specific genetic variants or a positive family history have been associated with an increased risk of developing prostate cancer. Men with specific genetic variants, such as pathogenic BRCA2 mutations, are at particularly greater risk of developing aggressive forms of prostate cancer and thus warrant undergoing careful screening for prostate cancer. However, the penetrance of many mutations in prostate cancer risk genes is unknown, and some men have no identifiable mutations in known risk genes despite a strong family history of prostate cancer. Prospectively collected clinical data along with biospecimens from unaffected individuals at high genetic risk for developing prostate cancer will advance the understanding of how specific mutations contribute to the development of prostate cancer and how these prostate cancers might be best detected. The purpose of this study is to prospectively screen men at high risk genetic risk for prostate cancer by prostate exam, PSA, and prostate MRI to characterize the penetrance and cancer-related outcomes of specific mutations, identify potentially novel genetic risk mutations and/or markers for early detection.

Study Timeline

• Study Start: 2020-02-12
• Study First Submitted: 2021-11-02
• Study First Submitted QC: 2021-11-09
• Study First Posted: 2021-11-22
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-05
• Last Update Posted: 2024-10-09
• Primary Completion: 2030-12
• Study Completion: 2040-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 400

Inclusion Criteria

• Men 35-74 years old
• No known diagnosis of prostate cancer
• Life expectancy >10 years
• Meet cohort A, B, or C criteria
• Cohort A: Documented pathogenic or likely pathogenic germline genetic mutation in a prostate cancer risk gene from a CLIA-certified laboratory (ATM, ATR, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, FANCA, GEN1, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51C, RAD51D, TP53)
• Cohort B: A strong family history suggestive of high genetic risk for prostate cancer with negative clinical genetic testing
• Cohort C: Individuals who self-identify as Black American or Black Caribbean with both parents and all four grandparents of Black/African ancestry

Exclusion Criteria

• Prior diagnosis or treatment of prostate cancer
• Inability to undergo prostate MRI
• Inability to receive MRI contrast agent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort A	Prostate cancer screening	Documented germline known pathogenic or likely pathogenic mutation in a prostate cancer related risk gene
Cohort B	Prostate cancer screening	Family history suggestive of high genetic risk for prostate cancer with clinical genetic testing negative for known pathogenic or likely pathogenic mutations in prostate cancer-related risk genes
Cohort C	Prostate cancer screening	Individuals who self-identify as Black American or Black Caribbean with both parents and all four grandparents of Black/African ancestry

Primary Outcome Measures

Name	Time	Method
Diagnosis of prostate cancer	From date of enrollment until date of diagnosis of prostate cancer or age of 75 reached, which ever came first	Diagnosis of overall and clinically significant (grade group 2 or higher) prostate cancer

Secondary Outcome Measures

Name	Time	Method
Positive predictive value of multiparametric MRI for detection of prostate cancer	From date of enrollment until date of diagnosis of prostate cancer or age of 75 reached, which ever came first	Positive predictive value of multiparametric prostate MRI for detecting clinically significant prostate cancer in men at high genetic risk for prostate cancer with a positive MRI (PI-RADS score of 3 or higher)

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States