Advanced image-identified extranodal extension of retropharyngeal lymph nodes in the refinement of N classification for nasopharyngeal carcinoma

Highlights•Anatomical factors of RLNs are positively correlated•Advanced RLN ENE is not an independent prognostic factor for NPC•N1/N2 NPC with advanced RLN ENE has a better prognosis than N3 diseaseSummaryAdvanced extranodal extension (ENE) in cervical lymph nodes (CLNs) increases the risk of distant metastasis in nasopharyngeal carcinoma (NPC). The 9th NPC staging system classifies N1/N2 patients with advanced CLN ENE as N3 due to similar outcomes. However, the prognostic impact of advanced ENE in retropharyngeal lymph nodes (RLNs) remains unclear. In this study of 4,485 patients with non-metastatic NPC, N1/N2 patients with advanced RLN ENE demonstrate better 5-year overall survival (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.38–0.93; HR: 0.57, 95% CI: 0.32–1.00) and failure-free survival (HR: 0.63, 95% CI: 0.44–0.92; HR: 0.52, 95% CI: 0.31–0.86) than N3 patients. Advanced RLN ENE shows a positive correlation with other RLN-related anatomical factors and is not identified as an independent prognostic factor. External validation in 3,849 patients from five centers supports these findings. Based on this evidence, upgrading advanced RLN ENE to N3 is not advised.Graphical abstract