Cachexia-Level Weight Loss Affected Nearly Half of Patients With Cancer

Weight loss meeting consensus criteria for cancer cachexia affected nearly half of patients in a large retrospective analysis, with episodes clustering around disease progression and associated with worse survival, according to a study published in Nature Medicine.

Investigators analyzed routinely collected clinicogenomic data from 52,236 patients profiled through the MSK-IMPACT prospective sequencing protocol at Memorial Sloan Kettering Cancer Center from 2010 to 2024. Using approximately 1.7 million BMI measurements, they identified discrete episodes of ≥5% weight loss over 6 months, or ≥2% for patients with a baseline BMI below 20kg/m², and linked those episodes to outcomes, serology, and tumor genotypes.

The investigators identified 30,938 episodes affecting 46.6% of patients. Prevalence was highest in pancreatic adenocarcinoma (72.7%) and stomach adenocarcinoma (71.7%). Ever meeting the weight loss criterion was associated with increased mortality risk in 17 of 18 cancer types analyzed, with glioblastoma as the exception (pan-cancer hazard ratio, 3.02). Radiographically confirmed progression events fell within episodes more often than expected by chance in 17 of 18 cancer types.

Across cancer types, episodes showed a consistent serologic signature, including lower albumin and hemoglobin and higher liver enzymes, although the authors noted that several of these markers may also reflect concurrent cytotoxic chemotherapy. TP53 mutations were associated with increased episode risk in nine cancers, including lung adenocarcinoma, and the association replicated in non-small cell lung cancer in an independent validation cohort of 5,785 patients from Dana-Farber Cancer Institute. Prediction models for lung, prostate, and colorectal cancer had concordance indices of 0.639 to 0.670; the authors described the model as "moderate in predictive power."

The authors noted that the findings establish associations rather than causation, that the single-center tertiary hospital design may limit generalizability, and that inadequate imaging data prevented use of the consensus criterion based on skeletal muscle index. They called for prospective interventional studies to validate the mechanisms and biomarkers identified.

Source: Castillon VJ, Xie AX, Boscenco S, et al. A health-system-scale, episode-resolved multimodal atlas of cancer cachexia. Nat Med. Published online October 12, 2026. doi:10.1038/s41591-026-04689-9