Subcutaneous adipose tissue loss as an early indicator of cancer cachexia in unresectable pancreatic cancer

PURPOSE: Body-composition indices beyond body mass index (BMI) are increasingly being investigated as prognostic cancer markers. In pancreatic cancer, the prognostic relevance of skeletal muscle and adipose tissue compartments remains uncertain, with studies yielding inconsistent findings. We examined whether early on-treatment changes in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle index (SMI) are associated with unresectable pancreatic cancer prognosis. METHODS: This retrospective cohort study comprised patients with unresectable pancreatic cancer who received chemotherapy between 2019 and 2024. Baseline and 3-month computed tomography (CT) scans at L3 were analyzed to quantify SAT, VAT, and SMI, calculating percent changes (Δ%). A 3-month landmark approach was applied to survival analyses. Associations with overall survival (OS) were examined using Cox models; discrimination with receiver operating characteristic curves; and survival differences using Kaplan-Meier and log-rank tests. RESULTS: Sixty-nine patients were included (median age, 71 years; median OS, 12.0 months). Greater preservation of SAT Δ% was associated with reduced mortality risk (HR per tertile step, 0.64; 95% confidence interval, 0.44-0.94), whereas VAT and SMI changes were not significant. SAT Δ% achieved the highest AUC for classifying short- vs long-term survival (0.73) compared with VAT (0.65) and SMI (0.52). The Kaplan-Meier analysis showed significant separation between extreme SAT tertiles (p = 0.02). CONCLUSION: Early SAT loss was more strongly associated with poor prognosis than concurrent VAT or SMI changes. Serial assessment of SAT on routine CT may enhance early risk stratification in unresectable pancreatic cancer.