Letter to the Editor “Feasibility of sentinel basin mapping after non-curative endoscopic resection for early gastric cancer: a prospective multicenter cohort study (SENORITA 2 Trial)”

Dear Editor, A valuable study explored the feasibility of sentinel basin mapping following non-curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC)1. In this prospective multicenter cohort study (SENORITA 2 trial), Park et al evaluated two mapping techniques, dual tracer and indocyanine green (ICG) fluorescence imaging in 238 eligible patients. Their findings, published in the International Journal of Surgery, offer valuable data on the detection rate and sensitivity of sentinel basin mapping, contributing meaningful insights to guide clinical decision-making. Nevertheless, we suggest that further discussion and investigation are warranted to strengthen the reliability and clinical applicability of these conclusions. In contrast to previous studies, which, despite limitations such as relatively small sample sizes or retrospective designs, have consistently demonstrated the feasibility of sentinel node navigation surgery (SNNS) after endoscopic resection (ER)2–6. These studies encompass both multicenter and single-center clinical cohorts, as well as observations from animal models, conducted in Japan and South Korea. Both the ICG fluorescence and the dual-tracer methods have shown high detection rates along with favorable sensitivity and accuracy. Given these discrepancies, and considering the SENORITA 2 trial’s finding of a notably elevated false-negative rate, particularly in the early phase (2017–2020) and at non-lead centers, with odds ratios of 4.11 and 4.00, respectively, along with the reported absence of false-negative cases at the lead center since 2019, the high false-negative rate observed in the trial warrants cautious interpretation. As emphasized in the article, the prolonged recruitment period and intermittent enrollment may have compromised the study outcomes. Consequently, the findings and overall quality of this research are likely insufficient to serve as conclusive negative evidence. Based on these findings, further clarification of the factors contributing to the higher false-negative rate observed in the early phase and at non-lead centers would strengthen the study. Additional analyses could explore the impact of the learning curve and assess whether enhanced procedural quality control for non-lead participating centers might lower the false-negative rate and improve the reliability. As evidenced in the SENORITA 2 trial, although sentinel basin mapping missed lymph node metastases in a small subset of patients (3.0%, 7/231), it could have preserved the stomach in 90.0% (208/231) of patients without nodal involvement. The trial also reported two postoperative deaths (0.8%), highlighting the inherent risks of gastrectomy and reinforcing the potential value of a less invasive strategy to avoid surgery. Therefore, from the perspective of EGC management, the risks and benefits of SNNS in this patient subgroup should be carefully weighed. Therefore, rather than dismissing the role of SNNS following non-curative ESD, its application warrants careful consideration through a balanced evaluation that weighs the potential risk of a false-negative outcome which affects approximately 3% of patients against the stomach-preservation benefit for the majority of patients. Second, although this study incorporated both dual-tracer and ICG fluorescence imaging, ICG fluorescence mapping was applied in only a limited number of cases, which restricts a comprehensive evaluation of its performance in this specific clinical setting. By contrast, Roh et al4 reported 98 patients who underwent ICG fluorescence lymphography-guided lymphadenectomy after ESD and demonstrated that ICG fluorescence imaging maintained a reliable negative predictive value and sensitivity (100%) for detecting lymph node metastasis. Given the current lack of standardization in ICG injection concentration and timing across studies, it remains to be investigated whether ICG fluorescence imaging as a standalone modality for SNNS following non-curative ESD would yield comparable results to those reported by Roh et al, and whether variations in ICG concentration or injection timing influence the sentinel lymph node detection rate and false-negative rate. Third, considering the reportedly low probability of skip metastasis in small EGC lesions, we were wondering how the authors interpret the relatively frequent occurrence observed in false-negative cases in this study. Further investigation using advanced detection technologies might help clarify lymph node drainage patterns after ESD, which would be valuable for guiding future research. Finally, we commend the authors for their significant contribution to advancing the field of EGC management. The SENORITA trial series represents a seminal and landmark body of work in the development of SNNS for EGC, establishing a critical foundation for future clinical and investigative efforts. Further investigation aimed at addressing the remaining challenges will be essential to refining the safety and efficacy of sentinel lymph node mapping following non-curative ESD. Ethical approval Not applicable. Consent Not applicable. Conflicts of interest disclosure The authors declare that they have no conflicts of interest or financial ties to disclose. Sources of funding This research was supported by National Key Research and Development Program of China (No. 2023YFC2507406), National Natural Science Foundation of China (No. 82300646), Beijing Natural Science Foundation (No. 7232334), Beijing Municipal Administration of Hospitals Incubating Program (No. PX2024002, PX2020001), Capital Fund for Health Development Scientific Research (No. 2024-2-2028), Beijing Municipal Science & Technology Commission AI+ Health Collaborative Innovation Cultivation Project (No. Z241100007724004), Research Ward Excellence Program of Beijing Municipal Health Commission (No. BRWEP2024W162020100, BRWEP2024W162020112, BRWEP2024W162020114), Excellent Plan for Capital Medicine Scientific and Technological Innovation Achievement Transformation Promotion Plan (No. YC202401QX0824), and Clinical Scientific Research Fund of Beijing Integrated Medical Association No. ZHKY-2025-1869 (B012). Author contributions J.Z. and J.Y.: conceptualization. Z.M.W. and Y.Y.J.: writing-original draft. Z.Z.: writing-review & editing. P.L. and S.T.Z.: supervision. Research registration unique identifying number (UIN) Not applicable. Guarantor Not applicable. Provenance and peer review Not applicable. Data availability statement Not applicable.