# The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS): A pragmatic trial of precision prostate cancer screening

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2024 · —

## Abstract

Prostate cancer is the most common non-cutaneous cancer in US men and among Veterans. Many cases are
non-lethal, but prostate cancer remains the 2nd leading cause of cancer death among US men. A major barrier
to reducing the incidence of prostate cancer metastasis and death is the lack of an optimal screening strategy
to identify men at high risk. Screening with prostate-specific antigen (PSA) testing modestly reduces prostate
cancer deaths but increases the morbidity associated with overdiagnosis and overtreatment. Current screening
approaches do not adequately distinguish men without prostate cancer or with low-grade prostate cancer
amenable to active surveillance from men with clinically significant prostate cancer (csPCa), who need
treatment. As a result, guidelines do not recommend universal prostate cancer screening. However, a new
paradigm of precision screening might improve the benefit-to-harm ratio of screening by implementing
screening strategies tailored to an individual's specific genetic profile. Germline genetic testing has emerged as
a powerful predictor for prostate cancer, including csPCa. This includes both rare highly penetrant variants and
polygenic risk scores (PRS), which characterize an individual's predisposition to prostate cancer due to
common genetic variation. Rare and common genetic variation is now an equally powerful predictor of
clinically significant disease as self-reported race or family history. This CSR&D Combined Proof of Concept
and Clinical Trial will evaluate the promise of precision risk stratification to identify men most likely to benefit
from prostate cancer screening. During the proof-of-concept phase, it will achieve the following: 1) Develop a
precision prostate cancer screening intervention consisting of genetic testing for rare variants and a
transancestry PRS for delivery to participants and their primary care providers along with individualized,
genetic risk-informed screening recommendations. 2) Determine the feasibility of enrolling men aged 55-70, at
least 35% of whom are of racial/ethnic minority groups, to a pragmatic randomized clinical trial (RCT)
comparing the precision screening intervention to usual care. 3) Perform an interim assessment to determine
whether the observed trajectory of prostate biopsy event rates is consistent with rates needed to detect a
meaningful between-group difference at the end of the 7-year project period. If feasibility of enrollment and
adequate event rates are demonstrated during the proof-of-concept phase, the RCT will continue to the clinical
trial phase to test the following co-primary hypotheses: 1) Compared with men in the usual care arm, men in
the precision screening arm will have a time-to-diagnosis of clinically significant prostate cancer (csPCa,
defined as NCCN classification intermediate risk or higher) that is not inferior by a margin of >30 days over a
median 4 years of follow-up; 2) Compared with usual care, men in the precision screening arm...

## Key facts

- **NIH application ID:** 10700379
- **Project number:** 1I01CX002635-01
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** Jason L Vassy
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-10-01 → 2028-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700379

## Citation

> US National Institutes of Health, RePORTER application 10700379, The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS): A pragmatic trial of precision prostate cancer screening (1I01CX002635-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10700379. Licensed CC0.

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