Study Explores Value of Prostate Cancer Screening With MRI
In This Article
- National rates of prostate cancer and death from the disease are high, but early detection can improve outcomes and reduce the intensity of treatment required
- Certain genetic mutations put some men at increased risk for aggressive forms of prostate cancer
- The Prostate Cancer Genetics Program at Massachusetts General Hospital is exploring whether MRI screening detects cancer earlier in men with genetic mutations known to promote the disease
- Initial results indicate that MRI was able to detect cancer that would have been missed by prostate-specific antigen testing and digital rectal examination, including aggressive disease (grade group 2 or higher)
Early results from a study at Massachusetts General Hospital indicate that prostate cancer screening with magnetic resonance imaging (MRI) successfully detects the disease in men with high-risk germline genetic variants—even when those patients had normal prostate-specific antigen (PSA) levels and digital rectal examination (DRE) results.
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"Certain genetic mutations are not only associated with an overall increased risk of prostate cancer but also an increased risk of more aggressive forms of the disease. So it stands to reason that identifying such cases early could give us a better opportunity to cure those patients," says lead author and principal investigator Keyan Salari, MD, PhD, director of the Prostate Cancer Genetics Program at Mass General. "Our study is looking at intensifying prostate cancer screening using not just PSA and prostate exams like we do for all patients, but also including MRI-based screening to enhance early detection in high-risk patients."
Initial findings suggest that MRI enhances early detection of prostate cancer, beyond the ability of DRE and PSA alone to detect disease. The results were presented at the 2023 Annual Meeting of the American Urological Association in May 2023.
A Unique Cancer Genetics Program for Families at High Risk
Prostate cancer is the most diagnosed cancer and the second most common cause of cancer death among men in the United States. Men with certain genetic mutations in genes such as BRCA1 and BRCA2 are at increased risk.
PROGRESS (Prostate Cancer Genetic Risk Evaluation and Screening Study) is a prospective evaluation of MRI-based screening for individuals at high genetic risk for prostate cancer. It aims to determine whether an enhanced screening protocol can increase cancer detection and ultimately improve outcomes in this population.
The study is being conducted at Mass General's Department of Urology and Prostate Cancer Genetics Program, part of the Center for Cancer Risk Assessment at the Mass General Cancer Center. The prostate program was the first of its kind in the country and is a unique resource for patients with a strong family history or hereditary predisposition to prostate cancer. Experienced genetic counselors, medical oncologists, and surgical oncologists with expertise in identifying at-risk families and individuals use specific screening tests to help detect the disease early.
PROGRESS is enrolling men ages 35–75 who have a documented pathogenic mutation in one of 19 genes associated with increased risk for prostate cancer but no prior prostate cancer diagnosis. Patients are excluded if they have a contraindication for MRI (such as claustrophobia or inability to receive the contrast agent) or a comorbidity that would limit lifespan within 10 years.
Each patient consults with Dr. Salari to discuss cancer risk based on family history and genetic testing results. Then patients receive a PSA blood test, DRE, and MRI at baseline. PSA and DRE will be conducted annually, with repeat MRI every three years.
Prostate Cancer Screening With MRI Detects Disease Missed by PSA and DRE
The first round of analysis was conducted on 81 patients in the initial cohort, with a median age of 55. Most have a pathogenic variant in either BRCA2 (39%, or 31 men) or BRCA1 (37%, or 29 men), with the rest of the cohort divided among the remaining gene mutation types.
In the first round of screening, two patients (3%) had an abnormal DRE, 10 (13%) had an elevated age-adjusted PSA, and 12 (15%) had a positive MRI. All 12 patients with an abnormal MRI, as well as one patient with a normal MRI but elevated PSA, then received prostate biopsy.
Six of those 13 patients (46%) had only abnormal MRI—PSA and DRE were normal. Of those 13 patients, eight (10%) were diagnosed with prostate cancer, four of whom were diagnosed with grade group two or higher disease. MRI screening did not miss any cancer in the cohort, but PSA failed to detect seven of the eight cases.
"If we weren't using MRI as part of the screening, it's quite possible that these patients would have their cancers eventually detected by PSA maybe two to five years later," Dr. Salari says. "But by using MRI and incorporating it into the screening protocol, we're detecting some of these cases earlier than we would have otherwise. And hopefully that translates to better outcomes for those patients in the long run."
It's particularly notable that the enhanced screening picked up more aggressive disease (grade group 2 or higher).
"Prostate cancer has a wide spectrum of disease aggressiveness. If all we were doing was picking up slow-growing, indolent prostate cancers earlier, that might not be as relevant because those cancers are not going to harm anybody, so you wouldn't be moving the needle in terms of outcomes," Dr. Salari explains.
In this niche group of men who have pathogenic mutations that make them more likely to develop aggressive forms of prostate cancer, early detection could make a difference in survival or the intensity of treatment they require.
PROGRESS Explores Best Screening Practices in Men With a Genetic Mutation for Prostate Cancer
PROGRESS is continuing to enroll patients and will follow them through additional rounds of screening. Dr. Salari says the results may ultimately help refine screening protocols and schedules among men with genetic mutations associated with prostate cancer. PROGRESS also has a parallel cohort of patients who are receiving MRI screening based on family history of disease, rather than a documented mutation.
"This approach with the MRI has promise, but we'll need more data and follow-up time to determine whether MRI screening should really be the best practice in certain men," Dr. Salari says. "But I certainly think that patients with these germline genetic mutations warrant careful monitoring, discussion, and shared decision-making about instituting prostate cancer screening from an earlier age."
He encourages primary care physicians, urologists, and genetic counselors to contact him if they have patients with relevant genetic mutations for potential enrollment in PROGRESS. Patients can be referred for specialized screening, even if they choose not to enroll in the study.
Learn more about the Prostate Cancer Genetics Program
Refer a patient to the Department of Urology