Androgen Deprivation Therapy in Prostate Cancer: Looking Beyond Prostate-specific Antigen and Testosterone Levels

Abstract

In this issue of European Urology, Nguyen et al. [1] review the important topic of the adverse effects of androgen deprivation therapy (ADT) and strategies to mitigate them. For>70 yr, ADT has been, and it remains, the most effective therapy we have for the treatment of advanced prostate cancer (PCa). I remember the variations in the use of ADT from one staff member to another when I was a urology resident. Somewould hold off on ADT in themetastatic state until symptoms arose, since there was no evidence that treating prior to symptoms made any difference. Others would readily perform a surgical castration on men with nonmetastatic and even early-stage PCa, since this form of therapy was often viewed as being the least morbid one in men who were judged to be too old or too frail for curative therapy. Some staff members regarded ADT as similar to hormonal therapy for women with breast cancer and suggested that lifelong ADT or castration (with or without local therapy) would lead to the best outcome. At that time, the only adverse effects of ADT that were discussed were the loss of libido/sexual activity and hot flushes. Shortly after coming on staff in 1992, I recall seeing the father of a rheumatologist, who had been diagnosed with metastatic PCa. He had remained cancer-free, with undetectable prostate-specific antigen (PSA), since a surgical castration performed 12 yr earlier. I was very proud of how well he had done but was saddened to see that he was bedridden and dying because of multiple osteoporotic fractures. The image lingered, but it was only a few years later that I would realize that his castration had controlled his cancer yet likely had contributed to his demise. All practitioners who treat PCa and use ADT now recognize that the adverse effects of ADT go beyond hot flushes and sexual problems, but unfortunately very little is actually done in day-to-day practice to proactively address these issues with the patient. Nguyen et al. very elegantly summarize the possible adverse effects of ADT and give practical evidence-based strategies to help minimize them. As physicians, we have a responsibility to recognize and identify patients at highest risk, andwe need to educate patients to be actively involved. Beyond the recognition and management of adverse effects, there is a need to constantly ensure that ADT is used appropriately and only when evidence exists for its use. We must also adopt strategies to minimize ADT exposure whenever possible. The recognition that the use of ADT is not inconsequential has been part of the driving force behind somevery important studies lookingat intermittentADT and reductions in ADT intensity in patients receiving radiation therapy. The following are some of the key points that I think are important regarding ADT’s adverse effects. First, bone health issues can be recognized, and effective therapies are available. There is no reason that physicians should continue to ignore this potential problem that can have significant consequences. Second, metabolic adverse effects are possible, and high-risk patients need to be recognized. Urologists are gatekeepers, but they probably are not comfortable managingdiabetes, cardiovascular issues, and lipids. They do have the responsibility of informing a patient’s family physician or internist that the ADT they prescribemay cause an imbalance that may be problematic in some patients. Third, fatigue is a very common complaint and should not be brushed aside. In my experience, fatigue is often the most troublesome adverse effect that a patient experiences. Patients need to be warned of this situation and address it proactively with exercise programs as early as possible. E U RO P E AN URO LOGY 6 7 ( 2 0 1 5 ) 8 3 7 – 8 3 8