Abstract
IMPORTANCE: Indocyanine green (ICG)-guided lymphadenectomy has been increasingly used to treat gastric cancer. However, its oncologic impact remains unclear. OBJECTIVE: To investigate the effect of ICG tracing on long-term outcomes in patients diagnosed with locally advanced gastric cancer undergoing neoadjuvant chemotherapy (NAC) followed by laparoscopic radical gastrectomy. DESIGN, SETTINGS, AND PARTICIPANTS: This retrospective cohort study included patients diagnosed with cT2-4N0/+M0 gastric adenocarcinoma who underwent NAC and laparoscopic radical gastrectomy at 3 teaching hospitals in China between January 2015 and June 2021, with follow-up data examined until June 2024. Overlap weighting (OW) was used to compare outcomes between the ICG and non-ICG groups. Results were tested for robustness using propensity score matching (PSM) and instrumental variable analysis. EXPOSURE: ICG-guided lymphadenectomy during laparoscopic gastrectomy. MAIN OUTCOMES AND MEASURES: The primary end points were 3-year survival outcomes, including overall survival (OS) and recurrence-free survival (RFS). RESULTS: Data from 459 patients (338 men [73.6%] and 121 women [26.4%]; mean [SD] age, 60.8 [9.9] years), of whom 119 underwent ICG-guided lymphadenectomy, were included. After OW adjustment, the ICG group exhibited a higher number of lymph nodes harvested (47.4 vs 38.3; P < .001) and better 3-year OS (78.6% vs 66.6%; P = .04) and RFS (74.0% vs 57.0%; P = .03) compared with the non-ICG group. Multivariable Cox regression analysis revealed that ICG tracing was an independent prognostic factor for both OS (hazard ratio, 0.59; 95% CI, 0.39-0.90; P = .02) and RFS (hazard ratio, 0.59; 95% CI, 0.40-0.87; P = .01), with the results remaining significant in both doubly robust and instrumental variable-adjusted models. Furthermore, in the OW-adjusted population, the OS benefit of ICG tracing was more pronounced in subgroups with ypN2/3 gastric adenocarcinoma (70.3% vs 36.2%; P = .01) and those achieving major pathological response (97.7% vs 77.6%; P = .04) (both P for interaction = .04). Similar results were obtained after adjusting for PSM. CONCLUSION AND RELEVANCE: In this study, ICG tracing was associated with enhanced lymphadenectomy and improved survival outcomes in patients with locally advanced gastric cancer after NAC. A prospective randomized clinical trial is needed to verify these findings.