ASO Visual Abstract: Prognostic Impact of Sarcopenia and Surgical Timing in Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Chemoradiotherapy-TIMES Study

BackgroundOptimal timing for surgery after neoadjuvant chemoradiotherapy (NCRT) remains controversial, necessitating reliable preoperative indicators. This study examines how sarcopenia and surgical timing affect prognosis in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Patients and MethodsThis retrospective study analyzed patients with LA-ESCC who underwent NCRT and surgery at three institutions in China from 2014 to 2023. The skeletal muscle area at the third lumbar vertebra was measured to calculate the skeletal muscle index (SMI). Prognostic analysis was performed using Cox proportional hazards models and propensity score matching (PSM), with survival curves generated using the Kaplan-Meier method and statistical significance set at p<0.05. ResultsA total of 415 patients were analyzed, with a median follow-up of 39.1 months. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 59.3% and 53.1%, respectively. Malnutrition and time to surgery (TTS) were independent prognostic factors for both OS and PFS (p < 0.05). Patients with long TTS showed better OS [hazard ratio (HR) = 0.62, p = 0.01] and PFS (HR = 0.68, p = 0.02) compared with those with short TTS. Among patients with sarcopenia, long TTS significantly improved OS (HR = 0.56; p = 0.01) and PFS (HR = 0.62; p = 0.02), while no survival benefit was observed for TTS in patients who were nonsarcopenic (p > 0.05). ConclusionsSarcopenia does not independently impact OS or PFS. Patients with sarcopenia benefit from a longer surgical time interval after NCRT. In addition, preoperative evaluation of muscle quality may aid in optimizing surgical timing to improve outcomes.