Genetic Testing for Prostate Cancer Screening

(ProGRESS Trial)

Overseen By Charles A Brunette, PhD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Prostate cancer, Prior biopsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

5000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve prostate cancer detection using a new genetic test. The goal is to determine if this test can identify men at high risk for serious prostate cancer and help those at low risk avoid unnecessary biopsies. Participants will receive a genetic risk report and personalized screening advice as part of the precision screening intervention. Men who have not had prostate cancer or related treatments and are Veterans receiving regular VA care might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to innovative research that could enhance prostate cancer detection and prevention strategies.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this genetic testing is safe for prostate cancer screening?

Research has shown that genetic tests for prostate cancer can identify men at high risk for serious forms of the disease, potentially reducing unnecessary biopsies. These tests do not require medication or invasive procedures, so they typically have no physical side effects.

The screening process uses genetic information from saliva, which is simple and non-invasive—no surgery or needles are involved. Participants receive a report detailing their risk level and screening advice, along with genetic counseling if needed.

Studies on similar genetic tests have demonstrated their general safety. Since no drugs or treatments are administered, the risk of side effects remains low. The primary goal is to use genetic information to guide screening decisions, leading to better outcomes by identifying those who truly need further tests or treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the precision screening intervention for prostate cancer because it offers a personalized approach to screening. Unlike traditional methods that may apply a one-size-fits-all strategy, this intervention uses a genetic risk assessment to tailor screening recommendations to the individual. This personalized method can potentially identify high-risk individuals more accurately and provide them with genetic counseling, aiming for earlier and more effective management of prostate cancer. Additionally, providing this information to both patients and their primary care providers ensures a more informed decision-making process.

What evidence suggests that this trial's precision screening intervention could be effective for prostate cancer screening?

This trial will compare a precision screening intervention with usual care for prostate cancer screening. Research has shown that genetic testing can identify men at risk for serious prostate cancer. A genetic risk score provides personalized risk estimates, potentially leading to more accurate screening. Studies have found that adjusting PSA levels based on genetics could prevent up to 31% of unnecessary negative biopsies, meaning fewer men might undergo unnecessary procedures. These findings suggest that genetic testing could improve screening by focusing on those truly at risk, helping to avoid unnecessary treatments for those who aren't. ^{1 5 6 7 8}

Who Is on the Research Team?

Jason L. Vassy, MD, MPH, SM

Principal Investigator

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Are You a Good Fit for This Trial?

The ProGRESS study is for male Veterans aged 55-69 who regularly receive care from the VA. It's designed to help those at risk of prostate cancer and aims to reduce unnecessary biopsies in men with low risk by using genetic testing.

Inclusion Criteria

Veteran status

Receipt of regular VA care

I am between 55 and 69 years old.

Exclusion Criteria

I carry a rare genetic variant linked to cancer.

I have had a prostate biopsy, surgery, or MRI before.

I have had prostate cancer in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Proof-of-concept

Develop a precision prostate cancer screening intervention and determine feasibility of enrolling men aged 55-70 to a pragmatic RCT

Not specified

Clinical Trial

RCT comparing precision screening intervention to usual care, testing co-primary hypotheses regarding time-to-diagnosis and biopsy rates

7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including prostate cancer diagnoses, PSA testing, and quality of life

7 years

What Are the Treatments Tested in This Trial?

Interventions

• Precision screening intervention

Trial Overview This trial tests a precision screening intervention based on genetic testing against usual care methods. The goal is to see if this new approach more accurately identifies men at high or low risk for significant prostate cancer.

How Is the Trial Designed?

Group I: Usual care Experimental Treatment 1 Intervention

Usual care in this study includes receipt of a brief brochure about shared decision-making in prostate cancer screening.

Group II: Precision screening intervention Experimental Treatment 2 Interventions

The precision screening intervention will consist of an interpreted prostate cancer genetic risk assessment (GRA) report, provided to the participant along with tailored prostate cancer screening recommendations and, in cases of high genetic risk, genetic counseling. The risk report and supporting educational materials will also be provided to the participant's primary care provider. Usual care in this study includes receipt of a brief brochure about shared decision-making in prostate cancer screening.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Genetic and genomic testing for prostate cancer is advancing rapidly, with DNA damage response gene defects now recognized as key predictors for the effectiveness of FDA-approved treatments like PARP inhibitors and immune checkpoint inhibitors in metastatic cases.

New technologies, including RNA expression tests and circulating tumor DNA analysis, are enhancing patient risk assessment and treatment personalization, making genetic testing essential for managing prostate cancer effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic and Genomic Testing for Prostate Cancer: Beyond DNA Repair. Herberts, C., Wyatt, AW., Nguyen, PL., et al.[2023]

A straightforward test can help identify men with advanced prostate cancer who have inherited gene mutations.

This identification allows for targeted precision treatments, potentially improving treatment outcomes for those specific patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate cancer gene test aids treatment precision. [2017]

Among 1,812 men with prostate cancer, multigene panel testing revealed a positive result rate of 9.4-12.1%, with BRCA1 and BRCA2 mutations found in 4.6% of cases, indicating the potential for targeted therapies.

Key predictors for positive genetic test results included higher Gleason scores and personal or family histories of certain cancers, suggesting that these factors should guide decisions for genetic testing in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosing hereditary cancer predisposition in men with prostate cancer. Pritzlaff, M., Tian, Y., Reineke, P., et al.[2022]

In a study involving 300 men aged 40-69 with BRCA1 or BRCA2 mutations, targeted prostate cancer screening using PSA testing showed a high positive predictive value of 47.6%, indicating effective identification of potential prostate cancer cases.

Out of the 11 prostate cancers diagnosed, 9 were in mutation carriers, highlighting that targeted screening can successfully detect clinically significant prostate cancer in high-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study. Mitra, AV., Bancroft, EK., Barbachano, Y., et al.[2022]

Prostate cancer is a major health issue in the U.S., with challenges related to screening and treatment, particularly due to concerns about overdiagnosis and overtreatment.

Recent advancements in molecular oncology highlight the genetic factors contributing to prostate cancer, suggesting that personalized, risk-adapted screening strategies could reduce the negative impacts of routine screening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetically Informed Prostate Cancer Screening. Arcot, R., Morgan, TM., Polascik, TJ.[2021]

Genetic testing for prostate cancer (PCa) is crucial, as hereditary factors account for up to 15% of cases, and recent guidelines emphasize testing for specific gene mutations like BRCA1/2 and CHEK2.

Implementing genetic testing in clinical practice can help identify young patients with aggressive tumors or those with a family history, allowing for early screening and targeted therapies, which could improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Insights on Genetic Testing in Primary Prostate Cancer. Kafka, M., Surcel, C., Heidegger, I.[2021]

Prostate cancer is influenced by genetic factors, with over 100 single-nucleotide polymorphisms (SNPs) linked to increased risk, and specific germline mutations in genes like BRCA1 and BRCA2 associated with moderate to high risks and more aggressive disease.

Targeted prostate screening using genetic information could improve early detection and treatment strategies, as men with certain DNA-repair mutations show a better response to therapies like PARP inhibitors, highlighting the potential for precision medicine in prostate cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Cancer Germline Variations and Implications for Screening and Treatment. Dias, A., Kote-Jarai, Z., Mikropoulos, C., et al.[2021]

Genetic-based screenings for prostate cancer are being researched as alternatives to traditional PSA and DRE methods, which have limitations in effectiveness.

This survey highlights both the innovations in genomic testing and the challenges that urologic clinicians may face in implementing these future interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Future Applications Of Genetic Prostate Cancer Screening in the Urologic Clinic. Feng, F., Schaich, M., Hughes, L.[2015]

A dedicated early detection clinic for high-risk men with known genetic variants related to prostate cancer has been established, enrolling 45 patients aged 35-75, primarily with pathogenic variants like BRCA1 and BRCA2.

Initial results show that out of 12 biopsies performed, 4 were positive for prostate cancer, indicating that this targeted screening approach may effectively identify cancer in genetically predisposed individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Findings from a High Genetic Risk Prostate Cancer Clinic. Sessine, MS., Das, S., Park, B., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05926102

NCT05926102 | The Prostate Cancer, Genetic Risk, and ... The precision screening intervention will consist of an interpreted prostate cancer genetic risk assessment (GRA) report, provided to the participant along with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7483627/

A genetic risk score to personalize prostate cancer ... PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS.

3. nature.com nature.com/articles/s41591-023-02277-9

Genetically adjusted PSA levels for prostate cancer ... We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05129605

Prostate Cancer Genetic Risk Evaluation and Screening ... 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8585808/

Updates in Prostate Cancer Research and Screening ... Therefore, the results of IMPACT so far confirm that PSA screening achieves early detection of aggressive PrCa in BRCA2 carriers. The results of the full 5 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12192897/

The Effectiveness and Harms of PSA-Based Prostate Cancer ... Conclusions: PSA-based screening offers modest mortality benefits but carries the risk of overdiagnosis. Precision diagnostics and risk-stratified strategies ...

7. sciencemediacentre.org sciencemediacentre.org/expert-reaction-to-23-year-follow-up-data-from-the-european-randomized-study-of-screening-for-prostate-cancer/

expert reaction to 23 year follow up data from The ... “The latest results show that PSA screening in this trial prevented 22 prostate cancer deaths per 10,000 men screened, compared to 14 deaths in ...

8. research.va.gov research.va.gov/for_veterans/progress.cfm

Prostate Cancer, Genetic Risk, and Equitable Screening ... The study uses genetic information from saliva to measure a participant's risk of developing prostate cancer. Enrolled participants are randomized to receive ...