CHICAGO—Metastasis-free survival or overall survival may be a more reliable and meaningful clinical endpoint than PSA relapse in studies of prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT), new findings suggest.
After discontinuation of ADT, testosterone levels take a long time to recover and, consequently, PSA levels may remain low in those with androgen sensitive PCa for a prolonged period of time. This can be a major confounding issue for clinical trials relying on PSA based endpoints in a pre-castrate resistant population.
“You need to look at testosterone recovery if you are going to follow PSA levels for study endpoints in the adjuvant setting,” said investigator Michael Schweizer, MD, a medical oncology fellow at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore.
Dr. Schweizer and his colleagues conducted a randomized phase 3 study of 228 men who received adjuvant ADT with or without docetaxel either immediately following radical prostatectomy or deferred until the time of biochemical relapse for high-risk PCa. They analyzed testosterone recovery data from 108 men who had at least one post-ADT testosterone measurement and completed the 18 months of ADT as specified by the protocol.
Median follow up time after the last dose of ADT was administered was 676 days. Testosterone recovered to more than 150 ng/dL in 90 men (83%) and to baseline in 64 men (59%).The study showed no significant differences in testosterone recovery between patients who received docetaxel and those who did not. The median time to testosterone recovery from the last day of treatment to a level greater than 150 ng/dL and to baseline was 306 days and 487 days, respectively.
After a median total follow-up of 3.4 years, 39 (17%) of the 228 patients had PSA progression and one patient experienced metastatic progression. Overall, the study indicated that recovery is prolonged after 18 months of hormone therapy, and PSA relapses occur late.
Clinical trials employing PSA-derived endpoints that routinely monitor testosterone levels and their correlation to PSA relapse with progression-free and overall survival may be highly beneficial, Dr. Schweizer said. Metastasis-free survival may be a better outcome measure because it is not confounded by testosterone levels, he said, adding that recent adjuvant trials have been designed to evaluate PSA progression as the primary endpoint.
Physicians should counsel their patients on prolonged courses of ADT that they should not expect their testosterone levels to recover to a meaningful level for at least a year or so, which can impact patients’ quality of life, Dr. Schweizer said. “I think patients need to understand that before committing to a long course of hormonal therapy,” he added.