Genetic Screening and MRI for Prostate Cancer
(PRS Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Adam S. Kibel, MD
Disqualifiers: Bleeding disorder, Heart failure, Angina, others
No Placebo Group
Trial Summary
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
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.
12345Is 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.
23467How 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.
23689Eligibility 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.
+3 more
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.
+1 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Low Risk CohortExperimental Treatment1 Intervention
Participants are placed into their arm after appropriate genetic testing has been conducted to determine their risk.
Group II: Intermediate Risk CohortExperimental Treatment1 Intervention
Participants are placed into their arm after appropriate genetic testing has been conducted to determine their risk.
Group III: High Risk CohortExperimental Treatment1 Intervention
Participants are placed into their arm after appropriate genetic testing has been conducted to determine their risk.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Walter Reed National Military Medical CenterBethesda, MD
Howard University HospitalWashington, United States
National Cancer InstituteBethesda, MD
Brigham and Women's HospitalBoston, MA
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Who Is Running the Clinical Trial?
Adam S. Kibel, MDLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Prostate cancer risk prediction using a polygenic risk score. [2021]Hereditary factors have a strong influence on prostate cancer (PC) risk and poorer outcomes, thus stratification by genetic factors addresses a critical need for targeted PC screening and risk-adapted follow-up. In this Finnish population-based retrospective study 2283 clinically diagnosed and 455 screen-detected patients from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC), 2400 healthy individuals have been involved. Individual genetic risk through establishment of a polygenic risk score based on 55 PC risk SNPs identified through the Finnish subset of the Collaborative Oncological Gene-Environment Study was assessed. Men with PC had significantly higher median polygenic risk score compared to the controls (6.59 vs. 3.83, P
Polygenic Risk Scores in Prostate Cancer Risk Assessment and Screening. [2021]More than 40% of the risk of developing prostate cancer (PCa) is from genetic factors. Genome-wide association studies have led to the discovery of more than 140 variants associated with PCa risk. Polygenic risk scores (PRS) generated using these variants show promise in identifying individuals at much higher (and lower) lifetime risk than the average man. PCa PRS also improve the predictive value of prostate-specific antigen screening, may inform the age for starting PCa screening, and are informative for development of more aggressive tumors. Despite the promise, few clinical trials have evaluated the benefit of PCa PRS for clinical care.
The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy. [2023]To date, the combined effect of polygenic risk score (PRS) and prostate health index (phi) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical centers from August 2013 to March 2019 were included. PRS was calculated on the basis of the genotype of 102 reported East-Asian-specific risk variants. It was then evaluated in the univariable or multivariable logistic regression models that were internally validated using repeated 10-fold cross-validation. Discriminative performance was assessed by area under the receiver operating curve (AUC) and net reclassification improvement (NRI) index. Compared with men in the first quintile of age and family history adjusted PRS, those in the second, third, fourth, and fifth quintiles were 1.86 (odds ratio, 95% confidence interval (CI): 1.34-2.56), 2.07 (95%CI: 1.50-2.84), 3.26 (95%CI: 2.36-4.48), and 5.06 (95%CI: 3.68-6.97) times as likely to develop PCa (all p < 0.001). Adjustment for other clinical parameters yielded similar results. Among patients with prostate-specific antigen (PSA) at 2-10 ng/mL or 2-20 ng/mL, PRS still had an observable ability to differentiate PCa in the group of prostate health index (phi) at 27-36 (Ptrend < 0.05) or >36 (Ptrend ≤ 0.001). Notably, men with moderate phi (27-36) but highest PRS (top 20% percentile) would have a comparable risk of PCa (positive rate: 26.7% or 31.3%) than men with high phi (>36) but lowest PRS (bottom 20% percentile positive rate: 27.4% or 34.2%). The combined model of PRS, phi, and other clinical risk factors provided significantly better performance (AUC: 0.904, 95%CI: 0.887-0.921) than models without PRS. Adding PRS to clinical risk models could provide significant net benefit (NRI, from 8.6% to 27.6%), especially in those early onset patients (NRI, from 29.2% to 44.9%). PRS may provide additional predictive value over phi for PCa. The combination of PRS and phi that effectively captured both clinical and genetic PCa risk is clinically practical, even in patients with gray-zone PSA.
A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data. [2021]A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening.
Recent Insights on Genetic Testing in Primary Prostate Cancer. [2021]Prostate cancer (PCa) is one of the most common cancers in developed countries. The results of large trials indicate that the proportion of PCa attributable to hereditary factors is as high as 15%, highlighting the importance of genetic testing. Despite improved understanding of the prevalence of pathogenic variants among men with PCa, it remains unclear which men will most benefit from genetic testing. In this review, we summarize recent evidence on genetic testing in primary PCa and its impact on routine clinical practice. We outline current guideline recommendations on genetic testing, most importantly, for mutations in BRCA1/2, MMR, CHEK2, PALB2, and HOXB13 genes, as well as various single nucleotide polymorphisms associated with an increased risk of developing PCa. The implementation of genetic testing in clinical practice, especially in young patients with aggressive tumors or those with positive family history, represents a new challenge for the coming years and will identify men with pathogenic variants who may benefit from early screening/intervention and specific therapeutic options.
Performance of Three Inherited Risk Measures for Predicting Prostate Cancer Incidence and Mortality: A Population-based Prospective Analysis. [2022]Single nucleotide polymorphism-based genetic risk score (GRS) has been developed and validated for prostate cancer (PCa) risk assessment. As GRS is population standardized, its value can be interpreted as a relative risk to the general population.
Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program. [2023]Genetic scores may provide an objective measure of prostate cancer risk and thus inform screening decisions. We evaluated whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with prostate cancer risk in a diverse population, including Black men, who have higher average risk of prostate cancer death but are often treated as a homogeneously high-risk group.
Association between a 17-gene genomic prostate score and multi-parametric prostate MRI in men with low and intermediate risk prostate cancer (PCa). [2018]We aimed to directly compare results from multi-parametric prostate MRI (mpMRI) and a biopsy-based 17-gene RT-PCR assay providing a Genomic Prostate Score (GPS) among individuals who were candidates for active surveillance with low and intermediate risk prostate cancer (PCa).
Application of European-specific polygenic risk scores for predicting prostate cancer risk in different ancestry populations. [2023]Polygenic risk score (PRS) has shown promise in predicting prostate cancer (PCa) risk. However, the application of PRS in non-European ancestry was poorly studied.