Improving Prostate MRI Screening for Genetically High-Risk Individuals
In This Article
- Prostate cancer is highly heritable; genetic factors explain roughly 57% of variation in individual risk
- The PATROL study evaluates combined age-adjusted PSA and upfront MRI screening in genetically high-risk men
- Data show that combined PSA/MRI screening finds more clinically significant prostate cancers in men with high-risk genetic mutations than either test alone
In addition to being the second-leading cause of cancer death among men in the United States, prostate cancer is one of the most heritable malignancies. For example, one study found that genetic factors can explain about 57% of the variation in prostate cancer risk.
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BRCA1, BRCA2, ATM, and PALB2 are among the genes associated with an increased risk of prostate cancer—and, in particular, aggressive prostate cancer. However, the optimal PSA thresholds for biopsy and utility of MRI for screening genetically high-risk individuals are not well-characterized.
"When these individuals are identified, we want to be able to screen them more closely starting at an earlier age and with a more intensive protocol so we can improve early detection of clinically significant prostate cancers," says Keyan Salari, MD, PhD, a urologic oncologist at Mass General Brigham Cancer Institute and director of its Prostate Cancer Genetics Program.
In 2020, Dr. Salari launched the PROGRESS study at Massachusetts General Hospital to evaluate the utility of prostate MRI as a screening tool in genetically high-risk individuals. He now serves as principal investigator at Mass General for the PATROL study, which is examining combined PSA/MRI screening strategies in this patient population.
Earlier study influenced NCCN guidelines
PROGRESS, a prospective study, evaluated the use of multiparametric MRI (mpMRI) as primary screening for prostate cancer in men who carry certain rare pathogenic germline mutations.
Results from the first 101 patients suggested that prostate mpMRI enhances early detection of any prostate cancer, especially clinically significant prostate cancer, when compared with traditional PSA screening. Based in part on these results from PROGRESS, the National Comprehensive Cancer Network incorporated prostate MRI into its updated prostate cancer guidelines for BRCA1/2 mutation carriers in March 2026.
More recently, working together with investigators at several other institutions, Dr. Salari has integrated PROGRESS participants into PATROL, a prospective, multi-institutional study with seven sites across the United States. The lead principal investigators are Heather Cheng, MD, PhD, and Daniel Lin, MD, of the University of Washington.
PATROL recruits individuals aged 40 years and older who carry a germline pathogenic variant in one of 14 known or suspected prostate cancer risk genes. Participants undergo screening with an annual PSA test and are encouraged to have an mpMRI at baseline and/or within one year of a prostate biopsy.
Participants are offered a biopsy if they have either of the following:
- An elevated PSA above specific age-adjusted thresholds (>1.0 ng/mL if <50 years, >1.5 if 50-59 years, >2.0 if ≥60 years)
- A suspicious mpMRI based on PI-RADS ≥3 lesion
"In the general population, a patient typically gets a PSA test for screening. Only if it's elevated does a clinician order a prostate MRI to get a radiographic assessment and then potentially proceed with a biopsy for diagnostic purposes," Dr. Salari says. "In this study, we've moved MRIs upfront as part of the initial screening for this high-risk population to evaluate whether that can improve the detection of clinically significant prostate cancer above and beyond PSA alone."
The primary endpoint of PATROL is to determine the positive predictive value (PPV) of the age-adjusted PSA thresholds and mpMRI for triggering a biopsy.
PSA and MRI found to work best in tandem
At the 2026 American Urological Association Annual Meeting, Dr. Salari reported the initial results of 264 PATROL participants who have had at least one PSA test and one mpMRI.
Of these individuals:
- Average age was 56.5 years.
- Median PSA was 1.16.
- 7% had a germline pathogenic variant in either BRCA1 or BRCA2.
Of the 89 participants who have had a biopsy due to a PSA or mpMRI abnormality, there was a 12.9% detection rate for any prostate cancer (PPV of 38%) and an 8.0% detection rate of clinically significant disease (PPV of 24%).
Interestingly, Dr. Salari says, two thirds of clinically significant cancers occurred in individuals with a PSA of less than 4—cases that conventional PSA thresholds would have missed. Furthermore, using age-adjusted PSA and mpMRIs in this high-risk population led to a higher PPV than conventional PSA thresholds for triggering a biopsy as well as superior net benefit on decision curve analysis versus PSA alone.
The investigators had hypothesized that the lower PSA cutoffs might allow them to detect more cancers in this high-risk population. Indeed, of the 89 participants who have been biopsied, the age-adjusted PSA caught 80% of the significant cancers. The mpMRI had a similar success rate.
Still, that means PSA and mpMRI each missed 20% of the significant cancers. "Both the lower PSA threshold and the MRI uniquely contributed to detecting the full set of clinically significant cancers that we identified," Dr. Salari says. "The takeaway is that neither PSA nor MRI alone does a perfect job; they perform best in tandem."
Dr. Salari acknowledges concerns that reducing PSA thresholds could lead to over-biopsying.
"But when you combine the age-adjusted PSA and upfront MRI strategy—while also considering that the incidence of prostate cancer is relatively higher in this patient population—our data suggest that this more intense screening approach is beneficial," he concludes.