MRI Enhances Early Detection of Prostate Cancer in Men at High Genetic Risk

The risk of early-onset and aggressive prostate cancer is elevated in men who carry certain rare pathogenic germline mutations. The prospective, multicohort Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS) is investigating whether prostate MRI would be a useful primary screening modality for these individuals.

Subscribe to the latest updates from Urology Advances in Motion

Error: Please enter a valid email address.

Email Address Submit

reCAPTCHA helps prevent automated form spam.

The submit button will be disabled until you complete the CAPTCHA.

In European Urology Oncology, Andrew E. Amini, MD, a resident physician in the Department of Urology at Massachusetts General Hospital, Keyan Salari, MD, PhD, director of translational research for the Department and director of the Prostate Cancer Genetics Program at Mass General Cancer Center, and colleagues report initial results from PROGRESS. They suggest prostate MRI is better at early detection of prostate cancer, including clinically significant cases, than prostate-specific antigen (PSA) screening alone.

MRI Was Often the Sole Basis for Biopsy

At the time of the report, 101 men had completed their first round of screening with digital rectal examination (DRE), PSA, and multiparametric MRI of the prostate. The participants were 35 to 74 years old and had a pathogenic germline mutation in any of 19 prostate cancer risk genes, most commonly BRCA1, BRCA2, ATM, or CHEK2.

Prostate biopsy was offered to the 24 patients who had an abnormality in at least one of the three screening tests. 21 patients underwent biopsy, and nine (42.9%) were found to have any grade of prostate cancer. Seven of the nine had clinically significant prostate cancer (csPCa, defined as grade group ≥2).

For detection of csPCa, abnormal MRI (grade ≥3 lesion) demonstrated 100% sensitivity and negative predictive value (NPV) of 100%, whereas PSA-based screening alone had 57% sensitivity and NPV of 73%.

MRI-based Screening Outperformed Other Strategies

Using the results from the patients, the researchers ran an analysis comparing six potential triggers for recommending biopsy:

1. PSA > age cutoff
2. Grade ≥3 lesion on primary MRI
3. Grade ≥4 lesion on primary MRI
4. MRI only if PSA abnormal, and grade ≥3 lesion detected
5. MRI only if PSA abnormal, and grade ≥4 lesion detected
6. PSA density >0.15 and grade ≥3 lesion on primary MRI

Applying trigger B would have resulted in the detection of the greatest proportion of csPCa cases (sensitivity 100% and positive predictive value [PPV] 42%). Applying trigger A would have caused the greatest proportion of unnecessary biopsies (6/10, 60%).

Triggers D and E would have had equivalent sensitivity in detecting csPCa (4/7 cases, 57%). However, compared with trigger D, trigger E would have had higher specificity (92% vs. 86%), PPV (80% vs. 67%), and NPV (81% vs. 80%). Trigger E would also have triggered the lowest proportion of unnecessary biopsies.

Net Clinical Benefit Greater With Primary MRI

Finally, the team compared the triggers while considering the time and cost associated with MRI. In the strictest scenario, they assumed the physician would be willing to pursue biopsy if there was a ≥5% risk the patient had csPCa. Under that assumption, trigger B achieved the greatest net clinical benefit, equivalent to detecting one additional csPCa case per 7.5 patients detected using age-adjusted PSA cutoffs, without an increase in unnecessary biopsies.

PROGRESS is continuing, and two other ongoing trials are also investigating prostate multiparametric MRI as primary screening for individuals at elevated genetic risk of prostate cancer.

view original journal article Subscription may be required

Learn more about the Prostate Cancer Genetics Program

Refer a patient to the Department of Urology