Cancer patients frequently develop loss of appetite and weight loss. Cachexia, defined by specific weight loss criteria, has a devastating physical and psychological effect on patients and caregivers. It results in a loss of muscle mass, altered body image, and associated decrease in physical functional level; it also often indicates the end of life. Cancer patients who have tumors responsive to chemotherapy often will regain weight. However, increased distress can result when cancer patients do not respond to treatment or experience treatment side effects, with weight loss sometimes eliciting requests from patients and their families for interventions to reverse cachexia.
In 2007, a panel of experts formalized the following definition: “Cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass.” Cancer cachexia cannot be easily reversed by increasing caloric intake and is distinct from starvation and age-related loss of fat-free mass. Before attributing weight loss to cancer, however, reversible contributing factors, such as depression, hyperthyroidism, or malabsorption, must be addressed. In a multi-institutional retrospective study of 3,047 cancer patients, weight loss occurring prior to the initiation of systemic chemotherapy, independent of disease stage and patient performance status, was predictive of disease progression and poor prognosis.
Cancer cachexia is characterized by an inflammatory state, insulin resistance, and loss of skeletal muscle due to protein breakdown and lipolysis. In cancer patients, it is associated with decreased caloric intake, anorexia, decreased muscle strength, and increased fatigue. Anorexia is common in cancer patients and results in decreased caloric intake, malnourishment, and weight loss. In advanced cancer, caloric intake is inadequate to support metabolic demands, which are often elevated due to an increased frequency of hypermetabolism.
In 2011, researchers in the field of cancer cachexia proposed a three-level distinct staging system consisting of pre-cachexia, cachexia, and a refractory stage. In advanced non–small-cell lung or gastrointestinal cancers, patients classified as pre-cachectic and cachectic according to the proposed cancer cachexia staging system were clinically similar with respect to overall symptom burden, quality of life, tolerance of chemotherapy, and survival, whereas those in the refractory stage were unique and were noted to have deteriorating clinical outcomes.
Estimates of the prevalence of cancer cachexia vary widely due to variable diagnostic criteria used in the past. In one study, more than one-half of 644 ambulatory cancer patients reported anorexia and weight loss exceeding 5% of premorbid weight. Cancer patients are often referred for cachexia intervention treatments late in their disease trajectory—that is, at a point where attempts to reverse the weight loss process may be less beneficial. In addition, healthcare professionals frequently under-recognize the prevalence of cancer cachexia, and this may contribute to delayed treatment of weight loss, often until the refractory stage.