Efficacy of immediate radiotherapy versus salvage radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma responsive to chemoimmunotherapy

BACKGROUND: Chemoimmunotherapy has become the standard first-line treatment for de novo metastatic nasopharyngeal carcinoma (dmNPC). However, the role and optimal timing of locoregional radiotherapy in dmNPC in the chemoimmunotherapy era remain unclear. This study aims to evaluate whether salvage locoregional radiotherapy (SLRRT), deferred until locoregional progression in patients with well-controlled distant metastases, compromises survival compared with immediate locoregional radiotherapy (ILRRT) in responders to first-line chemoimmunotherapy. PATIENTS AND METHODS: This retrospective cohort study included consecutive patients with dmNPC who achieved a complete or partial response after first-line platinum-based chemotherapy combined with anti-programmed cell death protein 1 therapy. The primary endpoint was overall survival (OS). Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline characteristics. Survival outcomes were assessed using Kaplan-Meier analyses and a multivariate Cox regression model. RESULTS: A total of 439 patients were included, with a median follow-up of 35.0 months (interquartile range, 24.0-45.2). Of these, 331 patients were assigned to the ILRRT cohort and 108 to the SLRRT cohort. After IPTW adjustment, SLRRT was not associated with inferior OS compared with ILRRT [2-year OS, 97.4% versus 90.1%; hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.54-1.59, P = 0.78]. SLRRT was associated with worse locoregional control (HR 4.78, 95% CI 2.98-7.66, P < 0.001) but better distant control (HR 0.62, 95% CI 0.41-0.95, P = 0.03). Radiotherapy-related adverse effects were substantially more frequent in the ILRRT cohort. CONCLUSIONS: Deferring SLRRT until locoregional progression did not compromise survival among responders to first-line chemoimmunotherapy. These findings support a response-adapted, de-escalated treatment strategy that may reduce treatment-related toxicities and improve quality of life without adversely affecting survival.