Exercise reduces mortality risk in pan-cancer population

Postdiagnosis exercise is associated with reduced all-cause mortality in patients with cancer across multiple sites, a pan-cancer analysis has shown.

“A high level of postdiagnosis exercise is associated with a significant survival benefit for several cancer types. However, most previous studies focused on a single cancer site, typically breast cancer, and few studies were conducted in colorectal or prostate cancer,” wrote the researchers. “The few available pan-cancer analyses are mostly characterized by a small overall sample size, resulting in a small number of patients for each cancer site. Whether the survival benefit differs on the basis of cancer site is unclear.”

The researchers used data from the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial to conduct a large-scale pan-cancer analysis (n=11,480; median age, 73 years; female, 40 percent) on the impact of postdiagnosis exercise on mortality. The primary diagnosis included >19 cancer sites, such as prostate (n=4,261), female breast (n=2,276), colon (n=872), skin (melanoma; n=773), bladder (n=535), and lung (n=391). [J Clin Oncol 2023;doi:10.1200/JCO.23.00058]

A total of 4,374 patients were exercisers (ie, moderate-intensity exercise for ≥30 minutes, ≥4 days per week or strenuous-intensity exercise for 20 minutes, ≥2 days per week), while 7,106 were nonexercisers. The primary endpoint was all-cause mortality, and secondary endpoints were cancer mortality and noncancer mortality.

After a median follow-up of 16 years from diagnosis, 4,665 deaths had occurred (cancer death, 1,940; noncancer death, 2,725). “The benefits of exercise are substantial. Median overall survival was 19 years in exercisers vs 14 years in nonexercisers, with a 25 percent risk reduction in all-cause mortality [hazard ratio (HR), 0.75; 95 percent confidence interval (CI), 0.70–0.80] in the pan-caner population,” highlighted Dr Lee Jones of the Memorial Sloan Kettering Cancer Center, New York, New York, US. “The reduction in all-cause mortality was apparent within 5 years, persisting for at least 20 years after diagnosis.”

The survival benefit was driven by reductions in both cancer mortality (HR, 0.79; 95 percent CI, 0.72–0.88) and noncancer mortality (HR, 0.72; 95 percent CI, 0.66–0.78).

The impact of exercise on mortality differed by cancer site. Exercise was associated with improved all-cause mortality for six types of cancer, including breast (HR, 0.76; 95 percent CI, 0.63–0.91), endometrial (HR, 0.41; 95 percent CI, 0.24–0.72), head and neck (HR, 0.62; 95 percent CI, 0.40–0.96), haematopoietic (HR, 0.72; 95 percent CI, 0.59–0.89), prostate (HR, 0.78; 95 percent CI, 0.70–0.86), and renal (HR, 0.50; 95 percent CI, 0.31–0.81) cancers.

“However, a significant reduction in cancer mortality in exercisers was observed only in head and neck cancer [HR, 0.49; 95 percent CI, 0.25–0.96] and renal cancer [HR, 0.34; 95 percent CI, 0.15–0.75],” Jones reported.

According to the researchers, exercise is a holistic strategy that may complement contemporary treatment approaches to further reduce cancer mortality in select sites (ie, neck and head, renal) while simultaneously reducing noncancer mortality, which translates to improved overall survival in the pan-cancer population.

“We have to be a little cautious. These are self-reported data that come with a lot of caveats,” Jones commented. “The contribution of unmeasured confounding, including diet and alcohol habits, cannot be disregarded.” Further data from randomized controlled trials are needed to prove causality.”

Jones’s research team is conducting a series of phase I–II trials to identify the recommended exercise dose for different cancer types. [https://www.mskcc.org/research-areas/labs/lee-jones/ongoing-clinical-trials]