Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)

Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)

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 or a positive family history 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.

Study Overview

• Status: Recruiting
• Conditions: Lynch Syndrome; Genetic Predisposition to Disease; Prostate Cancer; BRCA1 Mutation; BRCA2 Mutation; Prostatic Neoplasm; ATM Gene Mutation; MMR Mutation
• Intervention / Treatment: Diagnostic test: Prostate cancer screening

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 Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Olympia Price; Phone Number: 857-238-3838; Email: oprice@partners.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Men ages 35-74 years old at high genetic risk for prostate cancer on the basis of a specific germline genetic mutation or a strong family history.

Description

Inclusion Criteria:

• Men 35-74 years old
• No known diagnosis of prostate cancer
• Life expectancy >10 years
• Meet either cohort A or B 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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A; Documented germline known pathogenic or likely pathogenic mutation in a prostate cancer related risk gene	Diagnostic test: Prostate cancer screening; Physical exam (digital rectal exam), prostate-specific antigen (PSA) and PSA derivatives, and multiparametric MRI of the prostate
Cohort B; 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	Diagnostic test: Prostate cancer screening; Physical exam (digital rectal exam), prostate-specific antigen (PSA) and PSA derivatives, and multiparametric MRI of the prostate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of prostate cancer	Diagnosis of prostate cancer stratified by NCCN clinical risk category incorporating clinical stage, grade, and PSA at diagnosis.	From date of enrollment until date of diagnosis of prostate cancer or age of 75 reached, which ever came first, assessed up to 20 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive predictive value of multiparametric MRI for detection of prostate cancer	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)	From date of enrollment until date of diagnosis of prostate cancer or age of 75 reached, which ever came first, assessed up to 20 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Keyan Salari, MD, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2020
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2040

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 3, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: BRCA2; BRCA1; Mismatch Repair Deficiency; Lynch Syndrome; HOXB13; Family History of Prostate Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genital Neoplasms, Male; Prostatic Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Disease Susceptibility; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Genetic Predisposition to Disease
• Other Study ID Numbers: 2020P000081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No