Genetic Screening and MRI for Prostate Cancer

(PRS Trial)

Recruiting at 3 trial locations

Overseen By Daniella Furtado

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Adam S. Kibel, MD

Disqualifiers: Bleeding disorder, Heart failure, Angina, others

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

Compensation: Varies

Number of Visits: 2

1500 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Polygenic Risk Score, Genetic Risk Score, PRS for prostate cancer?

Research shows that using a Polygenic Risk Score (PRS) can help identify men at higher risk for prostate cancer, improving the accuracy of screening and potentially guiding earlier interventions. Studies have found that men with higher PRS are more likely to develop prostate cancer, and combining PRS with other clinical factors enhances the prediction of prostate cancer risk. ^{1 2 3 4 5}

Is genetic screening using Polygenic Risk Scores safe for humans?

The research articles do not provide specific safety data for genetic screening using Polygenic Risk Scores, but they focus on its potential to improve prostate cancer screening and risk assessment. ^{2 3 4 6 7}

How does the treatment Polygenic Risk Score (PRS) differ from other prostate cancer treatments?

Polygenic Risk Score (PRS) is unique because it uses genetic information to assess an individual's risk of developing prostate cancer, rather than treating the cancer directly. This approach helps identify individuals at higher risk, potentially improving early detection and personalized screening strategies, unlike traditional treatments that focus on managing or eliminating existing cancer. ^{2 3 6 8 9}

What is the purpose of this trial?

The goal of this clinical trial is to evaluate a screening method to detect clinically relevant prostate cancer. This clinical trial is using genetic data to determine a man's risk of cancer, together with multiparametric magnetic resonance imaging (mpMRI) to identify men with higher grade cancer. The main questions it aims to answer are: * If genetic data related to prostate cancer used with MRI can identify higher-grade, potentially fatal prostate cancer * What age a MRI is useful clinically for prostate cancer screening * If deep learning methods used with MRI when the genetic risk of the man is known can more accurately predict significant cancers Participants will: * Get a prostate specific antigen (PSA) blood test * Get an mpMRI * Get the results of their genetic data to determine if they are considered high-, intermediate-, or low-risk for prostate cancer based on the trials genetic testing * Follow-up for this trial based on the participants risk and findings from the PSA test and mpMRI

Research Team

Peter Pinto, MD

Principal Investigator

National Cancer Institute (NCI)

Adam S Kibel, MD, MHCM

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for men being screened for prostate cancer. It's especially focused on those who might have a higher genetic risk, determined by their Polygenic Risk Score (PRS). Participants will undergo an mpMRI scan and a PSA blood test to assess their cancer risk and need regular follow-ups based on these results.

Inclusion Criteria

No prostate MRI within the past 5 years

I am between 40 and 69 years old.

I have never had prostate cancer.

Exclusion Criteria

Unable to undergo an MRI

I don't have any severe illnesses that would make surgery risky.

I cannot have a biopsy due to bleeding or clotting issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Assessment

Participants receive a PSA blood test and mpMRI, and their polygenic risk score is determined

4 weeks

1 visit (in-person)

Risk Stratification

Participants are stratified into high, intermediate, or low risk cohorts based on genetic testing and mpMRI results

4 weeks

Follow-up

Participants are monitored for safety and effectiveness based on their risk and findings from the PSA test and mpMRI

1 year

Treatment Details

Interventions

• Polygenic Risk Score

Trial Overview The study is testing if combining genetic data with mpMRI can better identify serious prostate cancers that could be life-threatening. It also explores the best age for MRI screening and if deep learning improves predictions when genetic risks are known.

Participant Groups

Group I: Low Risk Cohort Experimental Treatment 1 Intervention

Participants are placed into their arm after appropriate genetic testing has been conducted to determine their risk.

Group II: Intermediate Risk Cohort Experimental Treatment 1 Intervention

Participants are placed into their arm after appropriate genetic testing has been conducted to determine their risk.

Group III: High Risk Cohort Experimental Treatment 1 Intervention

Participants are placed into their arm after appropriate genetic testing has been conducted to determine their risk.

Who Is Running the Clinical Trial?

Adam S. Kibel, MD

Lead Sponsor

Trials

1

Recruited

1,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 2283 prostate cancer patients and 2400 healthy individuals, a polygenic risk score based on 55 genetic markers was found to significantly predict prostate cancer risk, with higher scores indicating a greater likelihood of developing the disease.

Men in the highest quartile of the polygenic risk score were 2.8 times more likely to develop prostate cancer compared to those in the lowest quartile, suggesting that incorporating genetic risk factors can enhance screening and follow-up strategies for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate cancer risk prediction using a polygenic risk score. Sipeky, C., Talala, KM., Tammela, TLJ., et al.[2021]

Over 40% of prostate cancer risk is linked to genetic factors, with over 140 genetic variants identified that contribute to this risk through genome-wide association studies.

Polygenic risk scores (PRS) based on these variants can help identify individuals at significantly higher or lower risk for prostate cancer, enhance the effectiveness of prostate-specific antigen screening, and guide decisions on when to start screening, although clinical trials assessing their practical benefits are still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polygenic Risk Scores in Prostate Cancer Risk Assessment and Screening. Byrne, L., Toland, AE.[2021]

In a study of 3166 men undergoing prostate biopsy, a higher polygenic risk score (PRS) significantly increased the likelihood of developing prostate cancer (PCa), with odds ratios indicating a 5-fold increase in risk for those in the highest quintile compared to the lowest.

Combining PRS with the prostate health index (phi) and other clinical factors improved the predictive accuracy for PCa diagnosis, achieving an area under the curve (AUC) of 0.904, suggesting that this combined model is clinically useful, especially for patients with ambiguous PSA levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy. Ruan, X., Huang, D., Huang, J., et al.[2023]

The polygenic hazard score (PHS), which combines 54 genetic markers, can significantly influence the age at which men are diagnosed with clinically significant prostate cancer, with a 19-year difference in expected diagnosis age between the lowest and highest PHS percentiles.

Using PHS to adjust screening strategies could enhance the positive predictive value (PPV) of PSA testing, allowing for more personalized and effective prostate cancer screening based on individual genetic risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data. Huynh-Le, MP., Fan, CC., Karunamuni, R., et al.[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]

In a study of 208,685 participants from the UK Biobank, the genetic risk score (GRS) was found to significantly enhance the prediction of prostate cancer (PCa) incidence and mortality, identifying an additional 22% of men at higher risk compared to traditional measures like family history (FH) and rare pathogenic mutations (RPMs).

The GRS improved the ability to differentiate between men at risk for PCa, increasing the C-statistic from 0.58 to 0.67 for incidence and from 0.65 to 0.71 for mortality, indicating its effectiveness as a complementary tool in prostate cancer risk assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of Three Inherited Risk Measures for Predicting Prostate Cancer Incidence and Mortality: A Population-based Prospective Analysis. Shi, Z., Platz, EA., Wei, J., et al.[2022]

The polygenic hazard score based on 290 genetic variants (PHS290) was found to be a strong independent predictor of prostate cancer risk, including metastatic and fatal cases, in a study of 590,750 male veterans.

Men in the highest 20% of PHS290 had a 4.42 times higher risk of dying from prostate cancer compared to those in the lowest 20%, indicating that genetic scores can help tailor screening decisions for individuals based on their specific risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program. Pagadala, MS., Lynch, J., Karunamuni, R., et al.[2023]

In a study of 100 men with low and intermediate risk prostate cancer, there was a significant association between the Genomic Prostate Score (GPS) and multi-parametric MRI (mpMRI) findings, indicating that both tests provide valuable but different insights into cancer characteristics.

While GPS results varied significantly across different mpMRI categories, a wide range of GPS values was observed within each category, suggesting that mpMRI and genomic profiling may complement each other rather than replace one another in clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between a 17-gene genomic prostate score and multi-parametric prostate MRI in men with low and intermediate risk prostate cancer (PCa). Leapman, MS., Westphalen, AC., Ameli, N., et al.[2018]

The study found that a polygenic risk score (PRS) based on European ancestry can effectively predict prostate cancer risk in individuals of East Asian and African American ancestries, with those in the highest risk category having over 2.5 times the risk compared to average risk individuals.

Higher PRS not only indicated a greater likelihood of developing prostate cancer but also correlated with an earlier onset of the disease, suggesting that PRS can be a valuable tool for early detection across diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of European-specific polygenic risk scores for predicting prostate cancer risk in different ancestry populations. Ruan, X., Huang, D., Huang, J., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Prostate cancer risk prediction using a polygenic risk score. [2021]

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

Polygenic Risk Scores in Prostate Cancer Risk Assessment and Screening. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy. [2023]

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

A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data. [2021]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Performance of Three Inherited Risk Measures for Predicting Prostate Cancer Incidence and Mortality: A Population-based Prospective Analysis. [2022]

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

Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program. [2023]

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

Association between a 17-gene genomic prostate score and multi-parametric prostate MRI in men with low and intermediate risk prostate cancer (PCa). [2018]

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

Application of European-specific polygenic risk scores for predicting prostate cancer risk in different ancestry populations. [2023]