Defining optimal treatment strategies for nasopharyngeal carcinoma based on the ninth edition TNM staging system: insights from a multicenter cohort study in an endemic region
摘要
The ninth edition AJCC/UICC staging system (TNM-9) for nasopharyngeal carcinoma (NPC) was released in 2025, prompting a need to redefine evidence-based treatment regimens. This study aimed to identify optimal therapies under the new criteria.
MethodsIn this multicenter cohort, we enrolled patients from endemic Chinese regions (2016‑2017) with non‑metastatic (M0) or de novo metastatic (M1) NPC. Propensity score matching (1:1 or 1:M) and inverse probability of treatment weighting minimized selection bias. Survival was compared via Kaplan‑Meier and Cox models.
ResultsThe cohort comprised 6049 non-metastatic patients restaged by TNM-9 criteria, categorized into the following risk groups: low-risk (stage IA), intermediate-risk (stage IB and T3N0), high-intermediate-risk (T3N1), and high-risk (T1-3N2 and stage III). Additionally, 127 de novo metastatic patients were enrolled. Survival between concurrent chemoradiotherapy (CCRT) and intensity-modulated radiotherapy (IMRT) alone in the stage IA group was not significantly different (hazard ratio [HR]: 0.50; 95% CI: 0.05–5.50; P = 0.562). However, within the intermediate-risk group, CCRT demonstrated significantly improved 5-year OS (97.9% vs. 91.0%; P = 0.001). Among high-risk patients, induction chemotherapy (IC) followed by CCRT with or without adjuvant chemotherapy resulted in superior 5-year OS (83.9% vs. 78.6%; P = 0.003). Although reclassification under TNM-9 affected only a limited number of patients (n = 301), this subgroup exhibited a substantial survival benefit from the addition of IC (5-year OS: 83.2% vs. 66.4%; P = 0.001). A comprehensive treatment strategy combining systemic therapy, locoregional radiotherapy (LRRT), and maintenance therapy (MT) was associated with significantly prolonged survival (HR: 0.36; 95% CI: 0.23–0.55; and HR: 0.45, 95% CI: 0.25–0.79). Furthermore, local consolidation therapy of metastases (LCT) in M1a was associated with a non-significant trend longer median OS (89.0 vs. 62.4 months; P = 0.122).
ConclusionsUnder the TNM-9, management recommendations were as follows: radical IMRT alone for stage IA; CCRT for stage IB and T3N0; and high-intensity therapy for high-risk disease, including reclassified subsets. For metastatic disease, the addition of LRRT and MT to systemic therapy was associated with improved survival in both M1a and M1b patients, whereas a trend toward potential benefit from LCT was observed only in M1a subgroup.