Toward Wellness in Prostate Cancer Survivorship: Commentary on the AHA/ACS/AUA Advisory on Androgen Deprivation Therapy and Cardiovascular Disease

Twenty years ago, most physicians believed that all prostate cancer needed to be treated when detected. As recently as 10 years ago, more than 90% of men with low-risk clinically localized prostate cancer received some form of procedural intervention, usually with surgery, external beam radiation, or brachytherapy.[1] After publication of data describing the quality of life impact of prostate cancer treatment [2], physicians began to critically examine the burden that intervention places on the treated prostate cancer patient. Patients undergoing surgery or radiotherapy are now counseled regarding the possibility of well-described urinary, sexual, and bowel dysfunction.[3,4] These morbidities can substantially reduce patients' health-related quality of life. A proportion of men with prostate cancer who experience this negative quality-of-life impact regret their treatment choice and state that they would trade a shortened lifespan for the gain of preserved baseline genitourinary or bowel function.[5]

Treating physicians are now learning more about the impact of medical therapy for prostate cancer on the health and well-being of their patients, especially as it relates to androgen deprivation therapy (ADT). For ADT, observational data suggest an increased risk of pathologic fractures as a result of the induced osteopenia and osteoporosis.[6,7] There appears to be a dose-response effect whereby increasing the duration for which men remain on ADT increases the progressive risk of a pathologic fracture.[7] Herein, the American Heart Association, American Cancer Society, and American Urological Association (AHA/ACS/AUA) Science Advisory reviews the current literature on similar concerns regarding the relationship between ADT and the promotion of cardiovascular disease. Levine et al. succinctly review the current evidence for a causal role between ADT and cardiovascular disease that consists mostly of observational data and post hoc analyses of randomized trials of radiation and ADT. Analyses of nationally representative data sets demonstrated an increased risk of the development of metabolic syndrome and acute cardiovascular events for prostate cancer survivors on ADT compared with prostate cancer survivors never treated with ADT.[7,8] Although the existing evidence is insufficient to conclusively correlate ADT with cardiovascular disease, ADT does promote concerning metabolic changes associated with increased cardiovascular risk. The recommendations of the advisory are to monitor lipid profiles and glucose levels among all men on ADT and to ensure secondary preventive measures are adopted in men with a history of cardiovascular disease on ADT. These include rigorous lipid lowering, blood pressure control among hypertensives, and tight control of glucose levels among diabetics. Although the panel recommends communication between a urologist and primary care practitioner to emphasize the importance of cardiovascular surveillance in men on ADT, the urologist should ensure that ADT use is appropriate. Through the 1990s and early part of the 2000s, a substantial proportion of low-risk prostate cancer patients were subjected to ADT as primary therapy.[1] Although it is standard of care treatment for metastatic and recurrent prostate cancer, ADT is not curative and is not recommended by the American Urological Association as a standard option for men with clinically localized prostate cancer.[9] Data from the community cohort, Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), show that ADT as primary therapy peaked in 2000-2001, when it comprised 11% of treatment for men with low-risk prostate cancer. Following publication of data documenting potential morbidity of ADT and the enactment of the Medicare Modernization act of 2003, which lowered reimbursement for ADT injection, use of ADT dropped to 7% of the sample, with a corresponding increase in the use of active surveillance. Hopefully, changing incentives and emerging literature have refocused use of ADT on those patients with evidence documenting benefit. The advisory recommendations speak to a new paradigm of care for prostate cancer patients predicated on greater integration between the urologist and primary care practitioner. Quality of care in prostate cancer is measured through documentation of counseling, appropriateness criteria for medical testing, and the rate of complications and patient-reported outcomes.[10] Urologists must counsel men about the systemic effects of the therapies they prescribe to provide the highest quality of care. An addition to that measuring stick may be documentation of yearly laboratory tests relevant to the effects of ADT. Moving forward, we need to better understand the relative risks of ADT initiation versus active surveillance in men with recurrent disease. Many men are treated for biochemically recurrent prostate cancer before the onset of clinical metastases. We need to populate decision models with better data on the risks of ADT so that we may decide whether these outweigh the risks of not starting ADT.

We hope these recommendations promote more judicious and appropriate use of ADT and more concerted follow-up for those patients in whom the benefits outweigh the risks.