BERKELEY, CA (UroToday.com) - Following prostate-specific antigen (PSA) failure in patients treated with definitive radiation with and without androgen suppression therapy (AST), intermittent AST has been shown to be non-inferior to continuous AST with respect to survival. However, the optimal management at the time of PSA recurrence remains unknown with respect to comorbidity and PSA kinetics. To define randomized control trials (RCTs) to address this issue, we examined factors associated with the risk of death following PSA failure. Our study looked at the subset of 108 men, who were in a RCT of 70 Gy radiation therapy (RT) +/- 6 months of AST, who sustained a PSA failure and began AST when their PSA level approached 10 ng/ml. Cox regression multivariable analysis was used to determine whether PSA velocity at recurrence was associated with the risk of death, adjusting for other clinical factors (initial treatment, Adult Comorbidity Evaluation-27 comorbidity score, pretreatment PSA level, Gleason score, tumor category and age at and interval to PSA recurrence).
At 10.3 years of median follow up, increasing PSA velocity at recurrence was associated with a significant increase in the risk of death (AHR: 1.21; 95% CI: 1.02 to 1.45; P = 0.03). Amongst healthy vs unhealthy men (no or minimal versus moderate to severe comorbidity), prostate cancer (PC) comprised 42% (20/48) vs 12.5% (2/16) of all deaths, respectively. All-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) were significantly higher in men whose PSA velocity was greater than vs the median or less in the cohort of healthy men (P < 0.008) but not unhealthy men (P > 0.15). Hence, despite unfavorable PSA kinetics at recurrence, unhealthy men may not benefit from AST.
To our knowledge, there are no active RCTs to address the optimal management in men with non-metastatic, recurrent prostate cancer. There are 2 phase III studies in men with newly diagnosed high-risk prostate cancer who are being randomized to radiation therapy and long-term AST +/- a novel agent. First, RTOG 1115 is evaluating dose-escalated radiation therapy and standard ADT with a GnRH agonist +/- TAK-700 for men with high-risk prostate cancer. Second, the Dana-Farber Cancer Institute and the Trans-Tasman Radiation Oncology Group (TROG) are opening a RCT in the same population determining the benefit of adding enzalutamide to radiation therapy and long-term AST.
A RCT examining the impact on survival following intermittent AST vs surveillance is needed in unhealthy men with unfavorable PSA kinetics. For men in good health and unfavorable PSA kinetics at recurrence, PC death rates are high despite continuous AST, warranting RCTs evaluating the impact on death of adding novel agents such as abiraterone and enzulatimide to AST that prolong survival in men with metastatic castrate-resistant PC.
Miranda B. Kim, MD, MBA as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts USA