Upper Versus Middle-Neck Involvement in TNM-9 Stage IB Nasopharyngeal Carcinoma: Implications for De-Escalation and Intensification Strategies.

BACKGROUND: TNM-9 Stage IB nasopharyngeal carcinoma (NPC) encompasses markedly heterogeneous risk profiles, yet lacks reliable biomarkers to guide the choice between de-escalation and intensification strategies. This study aimed to explore the prognostic significance of upper- and middle-neck nodal involvement (UNI and MNI) in this population and how it affects treatment outcomes and prognosis. METHODS: Patients with Stage IB NPC treated between June 2016 and December 2019 at our institution were included. Nodal levels were classified into UNI and MNI. Survival outcomes, including overall survival (OS), progression-free survival (PFS), distant control (DC), and regional control (RC), were analyzed. RESULTS: A total of 370 patients were analyzed, with 257 (69.5%) classified in the UNI group and 113 (30.5%) in the MNI group, respectively. MNI was found to be associated with significantly worse prognosis compared to UNI. Specifically, the MNI group had lower 5-year OS (91.1% vs. 98.8%, p < 0.001), PFS (78.6% vs. 95.6%, p < 0.001), DC (90.2% vs. 98.8%, p < 0.001), and RC (93.3% vs. 98.4%, p = 0.005) than the UNI group. Association analysis revealed that nodal level was significantly associated with other known adverse prognostic factors, including the maximum diameter of positive lymph nodes, matted nodes, and high EBV-DNA levels (all p < 0.001). Crucially, after multivariate adjustment, nodal level is the only independent prognostic factor. CONCLUSION: The nodal level was a critical factor in predicting patient outcomes in Stage IB NPC. These findings are hypothesis-generating: UNI patients may represent a candidate population for prospective de-escalation trials, whereas MNI patients may warrant evaluation of intensified or novel strategies in future studies. Prospective validation is required before any change in clinical management.