Genetic Screening and MRI for Prostate Cancer

(PRS Trial)

Recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to detect prostate cancer by combining genetic information with advanced MRI scans. The researchers aim to determine if this approach can better identify serious cases of prostate cancer and establish the appropriate age for men to begin MRI testing. Men aged 40-69 who have not had prostate cancer or related tests in the last five years are suitable candidates for this study. Participants will undergo a PSA blood test, an MRI, and receive a Polygenic Risk Score (genetic risk assessment) to determine their risk level for prostate cancer—high, intermediate, or low. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research that could enhance early detection of prostate cancer.

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 prior data suggests that this screening method is safe for prostate cancer detection?

Research has shown that a polygenic risk score (PRS) safely assesses the risk of developing prostate cancer. This score uses genetic information to predict the likelihood of having prostate cancer.

Studies have found that PRS effectively identifies individuals at higher risk without causing harm. No reports link negative effects directly to PRS use, as it involves only genetic data analysis, not physical procedures. It is essentially a calculation based on genetic markers and does not involve medication or invasive procedures.

In simpler terms, this method is well-tolerated because it uses existing genetic information to assess risk. It is a non-invasive way to help doctors determine who might need further screening, such as an MRI (magnetic resonance imaging). Therefore, participating in a trial using PRS is likely safe, with no direct risks from the PRS itself. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses genetic screening and MRI to assess prostate cancer risk more accurately. Unlike traditional methods that primarily rely on age and PSA levels for risk assessment, this approach evaluates a Polygenic Risk Score (PRS) to provide a personalized risk profile. By categorizing participants into high, intermediate, and low-risk cohorts based on their genetic makeup, this method aims to improve early detection and tailor interventions more effectively. This trial could revolutionize how prostate cancer is screened and managed, making it more precise and potentially reducing unnecessary treatments.

What evidence suggests that this screening method is effective for detecting prostate cancer?

Research shows that a polygenic risk score (PRS) can help predict prostate cancer risk. In this trial, participants will join different risk cohorts—High, Intermediate, or Low—based on their PRS. Studies have found that a higher PRS indicates a greater chance of developing prostate cancer and being diagnosed at a younger age. This score relies on 130 genetic factors linked to prostate cancer risk. The PRS can also identify varying levels of prostate cancer severity, which is crucial for treatment decisions. Research across different ethnic groups suggests it reliably identifies individuals at higher risk. ^{1 2 6 7 8}

Who Is on the Research Team?

Adam S Kibel, MD, MHCM

Principal Investigator

Brigham and Women's Hospital

Peter Pinto, MD

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7617604/

Assessment of a Polygenic Risk Score in Screening for ... For persons diagnosed with PrCa at stage I/II, the 5-year survival rate is almost 100%; for persons diagnosed with stage IV disease, it is 50%.

2. nature.com nature.com/articles/s41598-024-71544-7

Predictive value of polygenic risk score for prostate cancer ... This hospital-based cohort study observed that a higher PRS was associated with increased susceptibility to prostate cancer and younger age of diagnosis.

3. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2407934

Assessment of a Polygenic Risk Score in Screening for ... We derived polygenic risk scores from 130 variants known to be associated with an increased risk of prostate cancer.

4. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2802030

A Polygenic Risk Score for Prostate Cancer Risk Prediction Two outcomes were examined: (1) any prostate cancer vs no cancer, and (2) GG of 2 or higher prostate cancer vs no cancer or a GG of 1 cancer.

5. elifesciences.org elifesciences.org/articles/78304

Validation of a multi-ancestry polygenic risk score and age- ... A previously developed multi-ancestry polygenic risk score is potentially an effective prostate cancer risk stratification tool across ancestry

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8100017/

Polygenic risk score for genetic evaluation of prostate ... Patients with high PRS had a 1.63-fold risk of BCR (95% CI, 1.454–1.826; p<0.001), and addition to clinical factors such as age, PSA, Gleason scores, ...

7. nature.com nature.com/articles/s41598-020-74172-z

Prostate cancer risk prediction using a polygenic risk score Men with PC had significantly higher median polygenic risk score compared to the controls (6.59 vs. 3.83, P < 0.0001). The polygenic risk score ...

8. cancer.gov cancer.gov/clinicaltrials/NCI-2024-04035

Polygenic Risk Score and MRI for the Detection of Prostate ... This clinical trial evaluates whether genetic data can be used along with magnetic resonance imaging (MRI) to improve the ability to detect prostate cancer.