Dan was in his late 70s when I started taking care of him. A retired Berkeley lawyer. Like so many patients his disease progressed through the usual steps of non-metastatic and asymptomatic, to metastatic and asymptomatic, and eventually to metastatic and symptomatic. He survived a long time but eventually succumbed to the disease.
One day, during a time when his PSA had to be in the 500 range, his bone scan revealed probably 15-20 discrete lesions, his testosterone was likely zero and his alkaline phosphatase was, I’m almost certain, on the rise, I dug in to gather some history on the extent to which his physical activity was winding down. I was stunned when he said “ I still go jogging every day…”
“Jogging?” I replied, incredulous. No doubt looking over the tops of my glasses, eyebrows raised, at him. A hallmark of incredulity if ever one existed. Not only did he jog, he jogged every day.
A glance at his wife offered validation. “He does” She affirmed. Her next expression suggested, however, that there may have been an alternate definition of “jogging” in the offing. A mental picture appeared. Perhaps a gray sweatsuit, a shuffle, and his white Tip O’Neill- haired head tilted to the side. Slow, but on the go. Turns out reality fit with my mental image. He only went about half a mile per day. And it took him 20-30 minutes. But he did it. That’s the point.
I have since taken to asking about physical activity as a kind of vital sign. In very advanced prostate cancer patients, those who are facing the end of life, and are winding down, I regularly gauge their prognosis by the amount of time they spend in bed. An afternoon nap? No problem, even I enjoy one of those from time to time. A nap after breakfast? That’s a red flag. In bed most of the day? Prognosis is probably weeks to months. Not getting out of bed? This signals that the body is shutting down.
These estimates are unscientific, and represent what I like to call the ‘parasitic’ effects of advancing cancer – as it progresses it robs the body of the resources it needs to thrive and survive – oxygen, water, protein etc. Initially this manifests as fatigue, then profound fatigue, then wasting and eventually, death. This is, of course, the far end of the cancer spectrum, but it is the sign of cancer winning the battle, of the body’s surrender to its effects.
But the typical CRPC patient endures years of treatment and disease control before he gets to the point when cancer limits his physical activity. And then there are stories like that of Dan – so it is somewhere during those years of enduring the cancer, where the endurance exercise of even jogging a mere ½ mile can be of benefit. I can’t help but think that this practice did something to keep Dan going for a few more months or years that he might have endured otherwise.
Even though I wrote, in a previous post, that sheer will is not sufficient to overcome cancer, I think there are points where will can slow it, and prolong life. I think it did so in Dan.
So is there a point when his physical activity may limit his cancer? I have come to think that there is. I am challenged by this notion however, because, unlike most of our oncologic interventions, we don’t know the mechanism of action of this therapy and what could be the confounding variables.
A couple of years ago I decided to take this on as a research question. This was in part because the expertise to do so was already in place at my institution, thanks to some research and retrospective data from some colleagues demonstrating that men with prostate cancer like Dan, who exercise 5 times per week or more, were almost half as likely to die (of the disease) than those who were diagnosed with prostate cancer and didn’t exercise.
But the other reason that I took it on, to be honest, was that I was skeptical. Coming off a series of successful clinical trials with abiraterone and its eventual FDA approval in the chemotherapy naïve setting, I had come to realize that to affect survival you will need a potent intervention, and to prove it you need to account for all the potential subsequent and confounding therapies that a patient may face. To put a lofty spin on why I decided to get involved I invoked the spirit of John F Kennedy’s call to the space race. To do the work to prove this, not because it is easy, but because it is hard.
Proving with a prospective clinical trial that exercise improves survival is going to be hard for a variety of reasons. But we are doing the trial. Here are some lessons learned already in this just-begun journey.
- Feasibility: Patients like to hear that exercise may help, and are generally willing to give it a shot. To do so, it needs to be made accessible and convenient for them.
- Broad spectrum of baseline fitness. Some patients are remarkably fit, even with progressing cancer, while others are not. The intervention of exercise, if it is going to help anyone, will help the latter not the former. They’re already benefitting.
- Broad spectrum of disease progression. Prostate cancer is a unique disease in its indolence in some patients. My hypothesis is that exercise may perturb its progression in those with an already indolent form. It’s not going to stop those with rapidly worsening disease.
- Aerobic vs Resistance? This is a big question. We don’t know which is better, or whether both are needed. This is the subject of ongoing studies.
- Academic medical centers, even clinical trial centers of excellence, aren’t particularly well suited to do this work. It requires dedicated facilities, exercise physiologists, and individual champions in the clinic.
We don’t know yet, but the preliminary data suggest its worth a study. My skepticism and the discipline that comes with research teaches me, however, that retrospective studies and the experience of observing patients like Dan can bias what we think to be true. Other factors that weren’t measured or observed may be behind these better outcomes. Thus, there is equipoise around the question. Plus, in prospective trials, we don’t test exercising versus doing nothing, we test supervised training versus what patients normally do. We don’t want anybody to do nothing.
The global Phase III study entitled INTERVAL-MCRPC (INTense Exercise foR surVivAL among men with Metastatic Castrate-Resistant Prostate Cancer), sponsored by Movember is underway in the US, Canada, Australia and several sites in Europe. A Multicenter, Randomized, Controlled Phase III Study. Accrual is underway. We’ll have results in a few years.
In the meantime, here’s a nod to Dan and those like him – keeping cancer…on the run.
Written by: Charles Ryan, MD, B.J. Kennedy Chair in Clinical Medical Oncology, Director and Professor of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota
Published Date: August 24th, 2017
Reference:
1. Ornish D, Lin J, Chan JM, et al. Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. The Lancet Oncology. Oct 2013;14(11):1112-1120.
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Prostate cancer - Evidence of Exercise and Nutrition Trial (PrEvENT): An Overview and Update: Beyond the Abstract