Prostate Cancer and the Therapeutic Benefits of Structured Exercise
- J. Kellogg Parsons⇑
-
Moores Comprehensive Cancer Center, University of California, San Diego; and San Diego Veterans Affairs Medical Center, La
Jolla, CA
- 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.
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.
AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
Footnotes
-
See accompanying article on page 335
REFERENCES
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