Cachexia — Cancer-Related Wasting Syndrome

Cachexia is defined as a systemic, multi-organ wasting syndrome driven by complex interactions between tumour metabolism and host immune response. It is characterised by severe, progressive loss of lean skeletal muscle mass, systemic inflammation, altered neuroendocrine function, and negative protein and energy balance. The diagnostic criteria typically include unintentional weight loss exceeding 5 percent over six months, or weight loss greater than 2 percent in individuals already displaying a low body mass index (BMI under 20 kg/m²) or sarcopenia.

The pathophysiology of cachexia involves elevated pro-inflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6). These signalling molecules alter hypothalamic appetite regulation, cause persistent anorexia, accelerate muscle proteolysis via the ubiquitin-proteasome pathway, and promote lipolysis. The clinical trajectory progresses through three stages: precachexia, cachexia, and refractory cachexia.

Cachexia significantly influences a patient's overall health and treatment trajectory. Loss of skeletal muscle reduces physical strength, stamina, and day-to-day functional independence, increasing the risk of falls and fatigue. Furthermore, muscle wasting diminishes a patient's tolerance to chemotherapy and radiotherapy, leading to increased treatment toxicity, required dose reductions, or unplanned treatment interruptions. Addressing cachexia early helps maintain resilience, improves comfort, and supports better tolerance of cancer-directed therapies.

There is no single diagnostic laboratory test for cachexia. Diagnosis relies on sequential tracking of body weight, calculating percentage weight loss over time, and measuring body composition through CT analysis, bioelectrical impedance, or dual-energy X-ray absorptiometry (DEXA). Blood biomarkers reflecting systemic inflammation—such as elevated C-reactive protein (CRP) and low serum albumin—are frequently assessed to monitor metabolic stress.

Cachexia occurs across many advanced malignancies, but it is particularly common in pancreatic, gastric, oesophageal, lung, and colorectal cancers, as well as head and neck tumours. Up to 80 percent of patients with advanced gastrointestinal or pancreatic malignancies experience some degree of cachexia during their disease course.

Managing cachexia requires a multimodal approach integrating optimal anti-cancer treatment to reduce tumour burden, personalised nutritional counselling with high-protein oral nutritional supplements, and light resistance exercise when feasible. Pharmacological options may include short-term corticosteroids or progestins (such as megestrol acetate) to stimulate appetite, and anti-inflammatory medications. Emerging therapies targeting specific inflammatory pathways remain under active clinical investigation.