Clinical Relevance of Physical Function Outcomes in Cancer Cachexia

Simple Summary Symptom management in the cancer setting focuses on the improvement of the overall quality of life and physical function, particularly for patients with muscle and weight loss, a syndrome known as cachexia, who suffer from low functional ability. Yet, there are no guidelines for measuring or defining low functional ability or standards for identifying meaningful changes in functional ability in response to disease and/or treatment. This unmet need is a major obstacle to developing new/improved therapies for cancer cachexia. This review presents the available evidence for identifying low functional ability and meaningful changes in functional ability in patients with cancer cachexia. Patients with cachexia may display a meaningful reduction in hand grip strength, which may be improved by interventions aiming to increase muscle mass. Future studies should confirm these observations in addition to identifying low functional ability and meaningful changes for other functional outcomes.Abstract Managing clinical manifestations of cancer/treatment burden on functional status and quality of life remains paramount across the cancer trajectory, particularly for patients with cachexia who display reduced functional capacity. However, clinically relevant criteria for classifying functional impairment at a single point in time or for classifying meaningful functional changes subsequent to disease and/or treatment progression are lacking. This unmet clinical need remains a major obstacle to the development of therapies for cancer cachexia. This review aims to describe current literature-based evidence for clinically meaningful criteria for (1) functional impairment at a single timepoint between cancer patients with or without cachexia and (2) changes in physical function over time across interventional studies conducted in patients with cancer cachexia. The most common functional assessment in cross-sectional and interventional studies was hand grip strength (HGS). We observed suggestive evidence that an HGS deficit between 3 and 6 kg in cancer cachexia may display clinical relevance. In interventional studies, we observed that long-duration multimodal therapies with a focus on skeletal muscle may benefit HGS in patients with considerable weight loss. Future studies should derive cohort-specific clinically relevant criteria to confirm these observations in addition to other functional outcomes and investigate appropriate patient-reported anchors.