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

Trial Summary

What is the purpose of this trial?

Prostate cancer is the most common non-skin cancer among Veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that healthcare providers screen male Veterans for prostate cancer.

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 data supports the effectiveness of the treatment Precision screening intervention for prostate cancer?

Research shows that using genetic information can help tailor prostate cancer screening to individual risk, potentially reducing unnecessary treatments and improving outcomes. Genetic tests can identify men with inherited mutations who may benefit more from specific treatments, making screening more precise and effective. ^{1 2 3 4 5}

Is genetic testing for prostate cancer screening safe for humans?

The research does not provide specific safety data for genetic testing in prostate cancer screening, but it focuses on identifying genetic predispositions to improve screening strategies. ^{3 4 6 7 8}

How is the Precision screening intervention treatment for prostate cancer unique?

The Precision screening intervention for prostate cancer is unique because it uses genetic testing to tailor screening strategies based on an individual's inherited risk, potentially reducing overdiagnosis and overtreatment compared to traditional methods like PSA (prostate-specific antigen) screening. ^{2 3 5 7 9}

Research Team

Jason L. Vassy, MD, MPH, SM

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prostate Cancer Germline Variations and Implications for Screening and Treatment. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Genetic and Genomic Testing for Prostate Cancer: Beyond DNA Repair. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Genetically Informed Prostate Cancer Screening. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Diagnosing hereditary cancer predisposition in men with prostate cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Prostate cancer gene test aids treatment precision. [2017]

6. England 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Initial Findings from a High Genetic Risk Prostate Cancer Clinic. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Recent Insights on Genetic Testing in Primary Prostate Cancer. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Current and Future Applications Of Genetic Prostate Cancer Screening in the Urologic Clinic. [2015]