Impact of Sarcopenia on Prognosis, Treatment Toxicity and Surgical Complications in Locally Advanced Gastric Cancer

Background: Weight loss and skeletal muscle wasting are frequent in cancer and may influence treatment tolerance and outcomes. Computed tomography (CT) based body composition analysis at the third lumbar vertebra (L3) is an accurate method to quantify skeletal muscle in routine oncology care. Methods: We performed a multicenter retrospective cohort study including 202 adults with locally advanced (stage IB-III) gastric cancer treated in four Portuguese hospitals (January 2020-December 2022). Skeletal muscle area (SMA) was assessed on baseline CT at the L3 vertebral level, using Data Analysis Facilitation Suite (DAFS) software v3.11.2, and skeletal muscle index (SMI) was subsequently calculated. Patients with low muscle quantity were classified as sarcopenic (below sex-specific SMI mean). We evaluated associations with relapse-free survival (RFS), overall survival (OS), FLOT chemotherapy dose-limiting toxicities (DLTs), and postoperative complications after gastrectomy. Results: Mean age was 69 years, 65% had ECOG PS 0, 53% received FLOT chemotherapy protocol. Mean SMI was 49.6 cm²/m² in males and 40.9 cm²/m² in females and correlated positively, though moderately, with BMI (p < 0.01; r = 0.424). Sarcopenia was not significantly associated with RFS (p = 0.186) or OS (p = 0.168) at 30-month follow-up. Although numerical differences were observed (64% vs. 56% of patients did not relapse and 74% vs. 63% were alive, for non-sarcopenic vs. sarcopenic patients). Sarcopenia was associated with a higher risk of DLTs (p = 0.021; OR 2.56, 95% CI 1.15-5.73) and postoperative complications (p = 0.024; OR 2.16, 95% CI 1.11-4.21). Conclusions: Sarcopenia significantly increases the risk of chemotherapy toxicity and postoperative complications in locally advanced gastric cancer. However, its effect on OS and RFS was not statistically significant at 30-month follow-up. Standardization of CT-based sarcopenia cut-offs remains a major barrier to clinical implementation.