The Link Between Ambulatory Dysfunction and Mortality in Cancer Survivors

Individuals with cancer often experience reduced mobility that persists long after the completion of treatment. In a study of patients undergoing outpatient cancer treatment, the most common functional problem was difficulty walking, and another study found that long-term (5 or more years) breast cancer survivors more frequently reported being unable to walk one-half of a mile compared with non-cancer control participants.¹

“The causes of ambulatory dysfunction are often multi-factorial and can result from loss of muscle mass, neurotoxicities including chemotherapy-induced peripheral neuropathy and vestibular impairments, fatigue, pain, and vision changes,” Kerri Winters-Stone, PhD, FACSM, exercise scientist and professor and section head of Cancer Population Science in the division of oncological sciences at Oregon Health & Science University in Portland, explained in an interview with Oncology Nurse Advisor.

Along with a significant negative effect on well-being, quality of life, and independence, research has demonstrated a link between ambulatory dysfunction and increased mortality among cancer survivors.^2,3 A study published in 2021 examined ambulatory function and associations with mortality risk among 30,403 cancer survivors and 202,732 cancer-free individuals.

The results revealed greater odds of walking at the slowest pace [odds ratio [OR], 1.42; 95% CI, 1.30-1.54) and being unable to walk (OR, 1.24; 95% CI, 1.17-1.31) among survivors compared with cancer-free participants, after adjustment for demographic variables, health status, and cancer type.³

Among survivors, those reporting the slowest walking pace showed increased risks of both all-cause mortality (HR, 2.22; 95% CI, 2.06-2.39) and cancer mortality (HR, 2.12; 95% CI, 1.83-2.45) compared with those reporting the fastest pace. Similar trends were observed for inability to walk.³

Lower ambulatory function was observed across 9 cancer types (breast, colon, oral, prostate, rectal, respiratory, soft tissue, stomach, and urinary cancers), with the strongest associations observed in patients with respiratory and oral cancers.³

“However, it should be noted that we did not have comprehensive treatment data, which varies widely depending on cancer type,” lead author Elizabeth A. Salerno, PhD, MPH, assistant professor of surgery in the division of public health sciences at Washington University School of Medicine in St. Louis, Missouri, told Oncology Nurse Advisor. “Our study provides some initial clues about these relationships, but we need more clinical and mechanistic research that explores if there are indeed differential associations by cancer type or treatment.”

Factors Driving Ambulatory Dysfunction and Mortality Risk in Cancer Survivors

Dr Winters-Stone posits that the stage of cancer and type of treatment may be more predictive of ambulatory dysfunction than the specific cancer site, with later-stage cancers likely to cause worse ambulatory dysfunction. “As for treatment, the more treatments someone has, the higher the potential risk of dysfunction is because symptoms and side effects can be widespread and cumulative,” she stated. “I would say that chemotherapy tends to be the biggest culprit in terms of dysfunction because the side effects and symptoms are widespread.” 

As one possible explanation for the connection between ambulatory dysfunction and higher mortality in cancer survivors, Dr Salerno proposed that ambulatory function may be a proxy for overall health. “We controlled for poor overall health to the best of our ability by adjusting for a frailty index comprised of 26 morbid conditions, as well as self-reported health status, and did not find striking evidence suggesting that poor overall health was responsible for our findings,” she said.³ “In observational studies such as this, however, we cannot completely rule out the possible impact of unmeasured or residual confounding.”

According to Dr Winters-Stone, it is also “possible that ambulatory dysfunction is a proxy for more aggressive cancer or multimodal therapies and thus is linked to mortality by association.” However, she noted that ambulatory dysfunction can increase the risk of falls, which can be life-threatening, as well as the risk of frailty. In addition, a decline in physical activity due to disability can increase the risk of chronic illnesses and cancer recurrence, and “if dysfunction progresses, a person may be more likely to be placed in a care facility and have poor survival.”

Dr Salerno explained that, to her knowledge, this was the first study to explore the relationship between cancer history, ambulatory function, and mortality in 15 different cancer types, and the next steps will involve further investigation into the underlying mechanisms.³ “More information about behavioral, biological, and cancer-specific factors across the entire cancer continuum, so both before, during, and after diagnosis and treatment will be important to better understand why ambulatory function is robustly associated with mortality,” she said.