Exercise scientist Lee Jones, PhD, led a first-of-its-kind clinical trial to investigate how exercise may affect treatment for prostate cancer at Memorial Sloan Kettering Cancer Center.
A clinical trial led by exercise scientist Lee Jones, PhD, at Memorial Sloan Kettering Cancer Center suggests that specific amounts of endurance exercise before surgery among men with early-stage prostate cancer can meaningfully improve two key biomarkers associated with better outcomes.
“To our knowledge, this is the first phase 1a clinical trial of exercise therapy in individuals with any type of cancer diagnosis,” says Dr. Jones, who is the head of the Exercise Oncology Program at MSK. The results of the clinical trial were published in JAMA Oncology in July 2024.
“We believe these results may be helpful for people facing this particular diagnosis and that this clinical trial represents an important step forward in rigorous investigation of how exercise impacts the progression and spread of cancer,” Dr. Jones adds.
Here he answers questions about the clinical trial.
Why did you do this research on exercise and prostate cancer?
We knew from research, including our own, that exercise (self-reported) is associated with a reduction in the risk of prostate cancer progressing. We have also found that men reporting regular exercise have a lower risk of dying from prostate cancer than those who report they did not exercise.
But that conclusion was based on data that had already been collected. So we had this interesting observation, but it hadn’t been rigorously tested in prospective trials in which we specifically “treat” men with controlled amounts of exercise therapy prescribed in the same way drugs are tested and prescribed — with a specific duration, number of times per week, and intensity.
And we had lots of questions, such as what is the maximum feasible amount of structured exercise that men with prostate can do with good compliance? And does exercise actually have any biological effect on the tumor itself? To answer these important questions, we needed to test exercise therapy directly.
Why did you decide to conduct a clinical trial to test the effects of exercise on prostate cancer?
I interact a lot with my colleagues at MSK, many of whom are medical oncologists testing new cancer drugs. I looked at the way that they develop drugs and thought we should investigate the effect of exercise therapy on cancer in a manner similar to how a drug is tested.
A phase 1 clinical trial with a new drug is designed to look at the safety and toxicity of that medication at different dose levels, to determine the most appropriate dosage to test in larger studies. An early phase trial also looks for biological activity that gives you a strong idea whether the drug is having an anti-tumor effect.
We took those same principles and applied them, for the first time, to exercise therapy in people with cancer. We already knew that exercise therapy was generally safe at lower dose levels in patients, but we didn’t know if exercise therapy would affect the biology of the tumor itself.
As with cancer drug trials, we wanted to know the most appropriate dose of exercise therapy that men could comply with and that also impacted the biology of the tumor. We call this the recommended phase 2 dose.
Why did you choose prostate cancer to study?
We knew from prior trials that exercise therapy helps men with the side effects of prostate cancer and its treatment. To test the effects on prostate cancer itself, we opted to do this in men who were scheduled to undergo surgery for their prostate cancer.
The reason for this is that we could examine how the tumor itself changed before and after exercise therapy by analyzing changes in the tumor itself from initial diagnosis and again at the time of surgery. At MSK, there is usually around four weeks between the time of diagnosis and the surgery to remove the tumor. That time can vary from one hospital to another.
That meant we had an approximately four-week window to test the effect of exercise therapy alone, when none of the participants had undergone any treatments such as radiation or chemotherapy.
How did you conduct the clinical trial?
To facilitate the rigorous conduct of this trial, our first priority was to make this as easy for the patients as possible. To do this, we developed the Digital Platform for Exercise (DPEx), a patient-focused approach where every aspect of the study (except the standard clinical procedures) takes place in the person’s home, rather than asking them to come to a clinic multiple times per week.
The trial participants included 53 inactive men. They ranged in age from 47 to 74 years. More than a third identified as nonwhite.
Our team then delivered a study kit to the patient’s home. It included a treadmill, an iPad pre-loaded with every app they would need, a smartwatch, a continual glucose monitor, a blood pressure cuff, and a digital scale.
Before starting exercise therapy, all men underwent a fitness assessment to ensure that exercise would be safe; we also used this information to personalize the intensity of the exercise therapy level.
We then enrolled men into increasing doses of exercise therapy. The lowest dose level we tested was 90 minutes (1.5 hours) per week. Once we found this dose could be done with good compliance, we then started to test higher doses, progressing to 150, 225, 300, 375, and, finally, 450 minutes (7.5 hours) per week.
All exercise sessions consisted of walking on a treadmill. The intensity ranged from easy to hard, and the duration of each session ranged from 20 minutes to 90 minutes, depending on the exercise dose level men were assigned.
For each session, participants would schedule a time to perform the planned workout on the study treadmill, and one of our exercise physiologists would monitor over Zoom in real time.
How did the clinical trial measure whether exercise affected the prostate tumor?
We measured two biomarkers associated with outcomes after a prostate cancer diagnosis.
The first is Ki-67, which is a marker of how fast cancer cells are dividing, or cancer cell proliferation. The second is PSA, or prostate specific antigen, which is a well-established biomarker for prostate cancer risk and progression. We were looking for a decrease in these biomarkers after various levels of exercise.
However, there is an important distinction to make in understanding the trial. We were using these biomarkers to help evaluate if exercise has any impact on the tumor—we’re looking for a “signal.” Our study did not investigate if exercise led to longer survival or better outcomes, because that will require larger and longer clinical trials.
What did the trial show about the necessary amount of exercise?
First, we found inactive men were able to consistently complete very high levels of exercise therapy — levels much higher than those typically tested in exercise and cancer studies. And no serious adverse events were observed, meaning the exercise everyone undertook proved safe for them.
Second, we concluded that 225 minutes (3 hours and 45 minutes) per week was the appropriate dose, meaning it was the lowest amount of exercise that was feasible but also improved the prostate cancer biomarkers we measured.
That’s 45 minutes of moderate exercise five times a week. Dose levels below 225 minutes per week did not impact the prostate cancer biomarkers, whereas 300 and 375 minutes were associated with similar reductions in the biomarkers but only slightly.
In other words, low levels of exercise did not have an impact, but beyond 225 minutes per week, more exercise was not better. This is a really important finding, at least from a prostate cancer perspective. Why ask people to do a massive amount of exercise if they don’t need to?
What are the next steps in your research on exercise as a treatment for cancer?
In close collaboration with Dr. Paul Boutros, a prostate cancer genomics expert at the University of California – Los Angeles, we’ve already begun a phase 2 clinical trial, using the 225-minute dose level to better understand how exercise can impact the progression of prostate cancer.
We also expect to start similar clinical trials for other solid-tumor cancers, including looking at whether cancers that have specific genetic mutations respond differently to exercise.
MSK is a leader in investigating the relationship between lifestyle factors, such as diet and exercise, and cancer. We look forward to using clinical trials to rigorously investigate what we see as the potential of exercise to help impact many kinds of cancer.