Stage-Specific Prognostic Impact of Longitudinal Body Composition Changes in Patients with Pancreatic Ductal Adenocarcinoma Treated with FOLFIRINOX: A Dual-Cohort Study

Background: Computed tomography (CT)-derived body composition has emerged as a promising prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). However, most previous studies have relied on baseline measurements and evaluated either resected or metastatic disease separately. We aimed to investigate the prognostic significance of both baseline and longitudinal CT-derived body composition changes in clinically distinct but therapeutically homogeneous cohorts of patients with PDAC receiving FOLFIRINOX. Methods: This retrospective single-center study included 98 consecutive patients with histologically confirmed PDAC treated with FOLFIRINOX between 2018 and 2025. Forty-seven patients underwent curative-intent resection followed by adjuvant modified FOLFIRINOX, whereas 51 patients with unresectable metastatic disease received first-line FOLFIRINOX. Skeletal muscle index (SMI) and visceral adipose tissue (VAT) were quantified on serial CT scans obtained at the third lumbar vertebral level before treatment and during therapy. Follow-up CT scans suitable for longitudinal body composition analysis were available for 46 of 51 patients (90.2%) in the metastatic cohort. Overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent prognostic factors. Results: Baseline CT-derived body composition parameters were not independently associated with survival in either cohort. In the resected cohort, preservation of visceral adiposity during treatment (follow-up VAT > 100 cm2) independently predicted improved OS in a multivariable model including three covariates (HR 0.460, 95% CI 0.220–0.960; p = 0.039). Median DFS and OS were 11.7 months (95% CI 6.5–16.9) and 20.9 months (95% CI 12.1–29.7), respectively. In the metastatic cohort, treatment-related skeletal muscle loss (ΔSMI) independently predicted inferior OS in a multivariable model including four covariates (HR 0.949, 95% CI 0.913–0.986; p = 0.008), while lung metastasis was also independently associated with worse survival (HR 5.792, 95% CI 1.880–17.841; p = 0.002). Median PFS and OS were 9.7 months (95% CI 8.0–11.4) and 12.7 months (95% CI 9.9–15.5), respectively. Conclusions: Longitudinal CT-derived body composition changes may provide additional prognostic information beyond baseline measurements in patients with PDAC receiving FOLFIRINOX. Preservation of visceral adiposity was associated with improved survival following curative-intent resection, whereas greater treatment-related skeletal muscle loss was associated with poorer survival in metastatic disease. These findings suggest that the prognostic relevance of body composition may vary according to disease stage and should be considered hypothesis-generating pending validation in larger prospective multicenter studies.