Active surveillance evaluated in men with low-risk prostate cancer with gene mutations

Findings from an analysis of short-term oncologic outcomes suggest that active surveillance may be a feasible strategy for management of low-risk prostate cancer in men carrying germline DNA repair gene mutations, concluded Israeli urologists who reported their experience in the Journal of Urology.¹ However, the authors emphasized as a caveat the need for close monitoring and cautious discussion of this option with patients, pending more outcomes data from larger patient cohorts with longer follow-up.

The paper reported on 15 men with germline DNA repair gene mutations who initiated active surveillance at the Rabin Medical Center in Petah Tikva, Israel, after receiving a diagnosis of low-risk (Gleason grade group 1) prostate cancer. Fourteen men (93.3%) were fully adherent to the active surveillance protocol, which included prostate-specific antigen (PSA) level measurement every 3 months and multiparametric MRI (mpMRI) and MRI-ultrasound fusion biopsy within 1 year and annually thereafter. During a median follow-up of 28 months, 3 men (20%) had upgrading at confirmatory biopsy and underwent definitive treatment, whereas the remaining 12 men (80%) continued on active surveillance without upgrading or treatment.

David Margel, MD, PhD, professor of urology in the Sackler Faculty of Medicine at Tel Aviv University in Israel and senior author of the paper, told Urology Times®, “This is the first prospective study that shows it is feasible to perform active surveillance among men with BRCA and other DNA repair gene mutations. Most physicians and patients are afraid to lose the window of curability in this situation. Our study comprises a small cohort with short follow-up, but our finding that the progression rate is similar to that seen in other active surveillance cohorts is encouraging.”

Commenting on the study, Leonard G. Gomella, MD, noted that germline testing is slowly finding its proper place in the management of prostate cancer. “Testing for germline DNA repair gene mutations is being used to inform decisions on screening and applied to treatment decisions such as active surveillance and in the management of advanced disease,” said Gomella, the Bernard W. Godwin Professor of Prostate Cancer and chairman of the Department of Urology at Thomas Jefferson University in Philadelphia, Pennsylvania.

The study encompassed the period between May 2014 and February 2019. It included a total of 18 men who had a diagnosis of very low- or low-risk prostate cancer and who were found to have a germline DNA repair gene mutation, the most common being in BRCA1 and BRCA2. All men had stage T1c and Gleason grade group 1 disease in up to 3 cores.

After receiving thorough counseling on active surveillance, 3 men chose to undergo definitive treatment. The 1 patient in active surveillance who was not fully adherent to the follow-up protocol declined to undergo fusion biopsy after being found to have normal PSA kinetics and no abnormalities in his mpMRI. Two men in active surveillance had implanted metallic devices that prevented them from having mpMRI, 1 had a confirmatory biopsy within 6 months after diagnosis because of a significant rise in PSA level, and a fourth man had not reached the 1-year follow-up.

Three men had upgrading on confirmatory biopsy to Gleason grade group 2 and underwent treatment with radical prostatectomy or focal high-intensity focused ultrasound. All 3 men had organ-confined disease and were free of biochemical recurrence at last follow-up.

Margel told Urology Times® that the group’s active surveillance cohort of men with low-risk prostate cancer who are germline DNA repair gene carriers now includes 24 patients.

“The progression rate in this expanded group is approximately 30%, and all the men who progressed had organ-confined disease,” he said.

“Germline DNA repair gene carriers are rare in the [patient population with] prostate cancer, and the only way to enroll a large active surveillance cohort will be through a collaborative effort. We are now trying to coordinate that with other groups in Israel,” Margel concluded.

Reference

1. Halstuch D, Ber Y, Kedar D, Golan S, Baniel J, Margel D. Short-term outcomes of active surveillance for low risk prostate cancer among men with germline DNA repair gene mutations. J Urol. 2020;204(4):707-713. doi:10.1097/JU.0000000000001027