Men whose prostate-specific antigen (PSA) level increases after radical prostatectomy or radiotherapy but who have no known metastases comprise the second-largest group of patients with prostate cancer. However, no standard of care exists for these patients, according to James Mohler, MD, Associate Director, Senior Vice President of Translational Research and Chair of the Department of Urology at Roswell Park Cancer Institute (RPCI).
In a review article that was recently published in the prestigious American Cancer Society journal Cancer, Dr. Mohler shares his expert perspective on the future of androgen-deprivation therapy for men with persistently increasing PSA levels after failed local therapy. He explains that earlier and more complete androgen-deprivation therapy may cure many men with advanced prostate cancer.
In the article, Dr. Mohler cites three randomized clinical trials that demonstrate the benefits of early androgen-deprivation therapy when used as neoadjuvant or adjuvant therapy for patients with high-risk localized disease. In one study, 36% of patients who were immediately treated with androgen-deprivation therapy vs. 55% of patients who received delayed therapy died within the median follow-up period of 11.9 years. Other findings have shown that intermittent androgen-deprivation therapy reduces side effects but does not affect survival.
Based on these findings, Dr. Mohler recommends using intermittent androgen-deprivation therapy at early stages of the disease. Additionally, newer agents may more effectively deprive prostate cancer of the androgens required for growth.
"The FDA has approved new agents for men with castration-recurrent prostate cancer after and more recently before chemotherapy," he says. "These agents extended survival, which shows they are quite potent. Now the question must be addressed as to whether they can extend remission or even cure men with prostate cancer who have not been cured by operation or radiation when co-administered with standard androgen-deprivation therapy."
Dr. Mohler also notes that existing evidence points to androgen-deprivation therapy in augmenting immune response, with preclinical data providing support for the combination of androgen-deprivation therapy and immunotherapy.
"If intracellular immunogens are spilled by prostate cancer cells, the combination of immune response and better androgen-deprivation therapy may allow 'clean-up' of the small amounts of truly androgen-independent prostate cancer that remains after androgen annihilation," he says.
Earlier and more complete androgen-deprivation therapy needs to be studied in preclinical models, the pre-prostatectomy setting and phase III clinical trials, according to Dr. Mohler.