Prostate Cancer and the Therapeutic Benefits 

of Structured Exercise

1. J. Kellogg Parsons⇑
   © 2013 by American Society of Clinical Oncology

+ Author Affiliations

1. Moores Comprehensive Cancer Center, University of California, San Diego; and San Diego Veterans Affairs Medical Center, La Jolla, CA

1. Corresponding author: J. Kellogg Parsons, MD, MHS, FACS, Moores Comprehensive Cancer Center, University of California, San Diego, 3855 Health Sciences Dr, #0987, La Jolla, CA, 92093-0987; e-mail: jkparsons@ucsd.edu.

© 2013 by American Society of Clinical Oncology

 For 70 years, androgen-deprivation therapy (ADT) has remained the foundation of treatment for advanced prostate cancer.¹ ADT with gonadotropin-releasing hormone agonists, gonadotropin-releasing hormone antagonists, or bilateral orchiectomy induces castrate levels of serum testosterone that promote apoptosis and regression of androgen-dependent prostate tumors. Indications for ADT include neoadjuvant or adjuvant settings treatment of aggressive locoregional disease, salvage treatment of recurrent disease after surgery or radiation, and primary palliative treatment of metastatic disease. ADT for the primary treatment of nonmetastatic prostate cancer is not routinely recommended.²

Androgen deprivation also compromises the essential anabolic functions of testosterone. The unintended consequences of ADT are far-reaching and reflect the fundamental roles androgens play in normal male physiology. ADT precipitates dramatic decreases in lean body mass, physical performance, muscle strength, and bone mineral density and corresponding increases in adiposity and osteoporosis. Other adverse outcomes include cardiovascular disease, diabetes, metabolic disturbances, cognitive impairment, hot flashes, depression, diminished sexual health, and chronic urinary symptoms.^3–5

ADT adverse effects are both potentially debilitating and difficult to manage. While utilization of intermittent rather than continuous dosing regimens modestly improves quality of life,⁶ and systemic therapy with bisphosphonates or denosumab reduces the risk of osteoporosis,⁷ efficacious options for mitigating most musculoskeletal and other adverse events otherwise remain frustratingly limited. 

Exercise—a simple, straightforward, and logical preventive strategy—has received relatively little attention in clinical practice and research. In the article accompanying this editorial, Gardner et al⁸ report the results of a thorough, well-performed systematic review of 14 published studies of 10 randomized trials of exercise interventions for patients with prostate cancer undergoing ADT. They conclude that resistance and aerobic training are highly effective at improving musculoskeletal outcomes in this population.⁸

Not surprisingly, the observed benefits of exercise in the setting of ADT are similar to those observed in healthy older adults, with ADT patients experiencing substantial improvements in muscular strength, endurance, cardiorespiratory fitness, performance of functional tasks, fatigue mitigation, and preservation of lean body mass. Interventions ranged from walking to weight training and included both supervised and unsupervised activities. Patients tolerated all of these interventions well; the frequency of adverse events was extremely low.

Notably, results were heterogeneous across studies and failed to demonstrate substantial improvements in adiposity, bone health, quality of life, urinary symptoms, erectile function, or metabolic markers. In addition, the potential benefits of exercise on prostate cancer progression and death are unclear. While some observational data suggest that increased physical activity inhibits clinical progression and reduces prostate cancer–specific mortality,^9,10 randomized trials have yet to be undertaken. Prospective exercise studies in patients with metastatic prostate cancer focused on survival end points would further elucidate these potential associations. 

Nevertheless, based on the data in this review, the evidence in favor of exercise is arguably strong enough to consider its routine implementation to diminish musculoskeletal adverse effects in patients with prostate cancer receiving ADT—particularly given the potential for exercise to also improve cardiovascular and overall health. Formally delivering efficacious exercise interventions for patients with prostate cancer will require the development of a novel infrastructure incorporating several key elements, including but not limited to the following: (1) designing cost-efficient delivery systems that provide equitable access for all patients, including those in lower socioeconomic brackets; (2) administering standardized, reproducible, and efficacious methods for increasing exercise; and (3) developing robust safety and quality control protocols.

Accomplishing these goals will require the coordinated efforts of oncologists, urologists, radiation oncologists, exercise specialists, and health policy experts. Consideration should also be given to the concomitant performance of T₃ and T₄ studies (http://www.ctsaweb.org/docs/CTSA+description.pdf) to assess the effectiveness of the translational process, verify outcomes, and determine the need for modified strategies. 

While the execution of these tasks might appear daunting, cardiac rehabilitation provides a relevant, successful model for incorporating supervised exercise into routine patient care. Cardiac rehabilitation programs, which primarily utilize exercise, produce compelling and consistent clinical results. Randomized trials have repeatedly demonstrated that cardiac rehabilitation reduces the probability of suffering additional cardiac events and is associated with a broad range of benefits, including reduced mortality. The interventions are reproducible and readily administered in an outpatient or home setting; some employ telephone outreach to administer therapy and monitor patient progress—techniques which, as Gardner et al demonstrated in this review, are feasible and efficacious in ADT patients.^8,11–13

Yet there also remains a broader, subtler barrier in pursuit of these endeavors: convincing potentially skeptical clinicians of the practical value of adding lifestyle modifications, such as exercise and diet,¹⁴ to the armamentarium of mainstream prostate cancer treatments. For both better and for worse, our action-oriented health care culture predominantly values technological innovation over less lucrative, more restrained pursuits; elegantly designed, enormously expensive systemic therapies and medical devices overshadow simpler yet scientifically valid approaches to patient care. Overcoming this bias will no doubt require educating, and perhaps even incentivizing, stakeholders as to the clinical value of exercise and advocating for its structured assimilation into the routine care of patients with prostate cancer.