Role of 5-alpha-reductase inhibitors in active surveillance of patients with low-risk prostate cancer.

Abstract

14 Background: Active surveillance (AS) is a recognized management option for low-risk prostate cancer. Many institutions use serial PSA values to determine when to reclassify patients into higher risk categories. The impact of 5-alpha-reductase inhibitors (5-ARIs) in this setting has not been well studied. The purpose of this retrospective review was to compare PSA doubling time prior to the initiation of a 5-ARI (pre-5-ARI) to that after the PSA nadir (post-nadir) has been reached. Methods: Between 1996 and 2010, a total of 100 patients with a history of 5-ARI use were captured from our AS database. Of these, twenty-nine had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir doubling times. The majority had stage T1c disease (89.7%) and Gleason scores of six or lower (93.1%). The average PSA at presentation was 6.93 µg/L. More patients were prescribed dutasteride (79.3%) than finasteride (20.7%). PSA doubling time was calculated using the general linear mixed-model method. Statistical analysis was performed using the non-parametric sign test. Results: Median follow-up was 69.5 months (mo). For the twenty-nine patients analyzed, the median pre-5-ARI PSA doubling time was 55.8 mo (6-556.8 mo), while that for the post-nadir values was 25.2 mo (6-231 mo) (p=0.0081). Six patients were ultimately reclassified after an average of 67.7 mo (59-95 mo), due to progression in either PSA doubling time (n=2) or Gleason score (n=4). The median pre-5-ARI and post-nadir doubling times for this group were 48.2 mo (32.4-91.1 mo) and 23.3 mo (6-44.3 mo), respectively. Five of the patients underwent radical prostatectomy, while one underwent radiotherapy with androgen deprivation. Of the six patients, one had biochemical failure after an average post-treatment follow-up of 21.3 mo (0-52 mo). Conclusions: In AS for low-risk prostate cancer, it was found that 5-ARIs significantly decreased PSA doubling time. This effect may be related to preferential suppression of benign prostatic tissue, thereby providing a more accurate depiction of the true cancer-related doubling time. If validated with a larger cohort, 5-ARIs may enhance the utility of PSA doubling time as a biomarker of disease progression in AS.