In a randomized controlled trial, researchers at Duke University demonstrated a benefit for men who participated in a supervised exercise program prior to starting on ADT. That will come as no surprise to anyone who has been following the recommendations of the ADT Educational Program.
In the Duke study, half the participants got “usual care” without a specific exercise program. The other half got 48 consecutive, one-on-one, personalized exercise sessions (three per week for 16 weeks) with a trained exercise specialist. Patients started on standard ADT plus enzalutimde (=Xtandi) a month after starting the exercise program. The exercise regime involved both aerobic and resistance training.
Those in the exercise group demonstrated improved cardiorespiratory fitness plus improved lower body strength and physical function after 17 weeks. The study thus affirmed the advantage of starting exercise before starting ADT. The authors speak of this as initiating exercise “proactively” in order “to prevent toxicity, rather than recover from establish toxicity”; i.e., “prehabilitation“ rather than “rehabilitation“.
This is all well and good. No surprises there. If one is starting on androgen deprivation—whether with a single drug or with a combination of drugs—one is better off being fit and exercising before one begins experiencing ADT side effects than trying to recover fitness after having been challenged by the drugs.
There are, however, a wealth of problems with this study.
To start with, the study failed to meet its accrual targets. The authors aimed to have 28 patients in each group; instead, they ended up with less than half of the target; i.e., only 13 patients per group. The authors acknowledged that they closed their study early due to poor accrual. This is particularly problematic considering that there are 19 (!) authors on this study, of whom many were physicians who should have been able to help with accrual.
One wishes that the authors had discussed their recruitment challenges in greater detail. They briefly suggest that the study suffered from the fact that the exercise intervention was offered at only two sites, which may have been difficult for many patients to get to. They also suggest that there may be hesitance among men invited to the study because of “anxiety resulting from delaying ADT to undergo exercise testing and training prior to starting [hormone] therapy.“ But the authors do not say whether they surveyed individuals, who declined to participate. Such data may have offered insight into the actual barriers to participation.
What is also missing from this paper is what the study cost. It can be pretty expensive to have one’s fitness assessed in training sessions three times a week with a one-on-one personal trainer. We’re told that the researchers and the drug company that funded the study agreed to close it early. Presumably it simply wasn’t financially sustainable.
From a practical sense, the study failed for logistical, financial, and possibly other reasons that are not specified. However, from a patient’s perspective the conclusion is clear.
If one’s oncologist says one should start on ADT, one should also get started with an exercise program ASAP…before the side effects of the drugs begin and, if possible, even before commencing ADT. The important thing is to get started with an exercise regimen that is attainable and sustainable for each individual.
Many cancer centres now offer free or low-cost exercise resources that can support people’s efforts to incorporate physical activity into their lives. You can find links to online exercise resources on our website at: https://www.lifeonadt.com/links
To read the study abstract, see: https://pubmed.ncbi.nlm.nih.gov/35273377/
Reference:
Harrison MR, Davis PG, Khouri MG, Bartlett DB, Gupta RT, Armstrong AJ, McNamara MA, Zhang T, Anand M, Onyenwoke K, Edwardson S, Craig D, Michalski M, Wu Y, Oyekunle T, Coyne B, Coburn A, Jones LW, George DJ. A randomized controlled trial comparing changes in fitness with or without supervised exercise in patients initiated on enzalutamide and androgen deprivation therapy for non-metastatic castration-sensitive prostate cancer (EXTEND). Prostate Cancer Prostatic Dis. 2022 Mar 10. doi: 10.1038/s41391-022-00519-4. Epub ahead of print. PMID: 35273377.