Weight loss and longitudinal weight trajectories during neoadjuvant chemoradiotherapy predict survival after esophagectomy for locally advanced esophageal squamous cell carcinoma

Abstract Background Weight loss frequently occurs during neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, whether the prognostic significance of weight loss differs across treatment phases has not been well defined. Methods We retrospectively reviewed 377 patients with LA-ESCC who received NCRT followed by curative esophagectomy between 2017 and 2023. Body weight was collected at predefined milestones spanning treatment initiation to the early postoperative period. The associations between phase-specific weight loss and survival outcomes were examined using multivariable Cox regression models. Patterns of longitudinal weight change were characterized using latent class trajectory analysis. Results Over a median follow-up of 60.2 months. Weight loss during NCRT emerged as an independent predictor of both poorer OS (hazard ratio[HR] 2.21, 95%CI 1.39–3.51, P = 0.001) and PFS(HR 1.87, 95% CI 1.23–2.84, P = 0.003). Weight loss during the interval between NCRT completion and before surgery was also associated with inferior OS(HR 2.0, 95%CI 1.18–3.4, P = 0.01). In contrast, weight changes before treatment initiation and during the early postoperative period were not associated with survival. Four distinct weight trajectories were identified. Patients with a low gradual decrease trajectory had significantly worse outcomes compared with those whose weight remained stable or increased(HR 2.35, 95% CI 1.4–3.95, P = 0.001). Mortality risk increased progressively with greater weight loss during NCRT. The prognostic impact of weight loss was particularly evident among patients treated with paclitaxel–carboplatin and those with a higher baseline performance status. Conclusions Among patients with LA-ESCC undergoing trimodality treatment, weight loss during NCRT—but not at other treatment stages—was associated with survival after esophagectomy. Longitudinal weight trajectories provided complementary prognostic information beyond conventional assessments of weight change.