Defining the role of locoregional radiotherapy for de novo metastatic nasopharyngeal carcinoma in the immunotherapy era: A systematic review and meta-analysis.

6039 Background: In the pre-immunotherapy era, a phase 3 randomized controlled trial (NCT02111460) confirmed locoregional radiotherapy (LRRT) combined with palliative chemotherapy improved overall survival (OS) and progression-free survival (PFS) in de novo metastatic nasopharyngeal carcinoma (dmNPC). Consequently, this strategy has been adopted by major clinical practice guidelines, including NCCN, CSCO, and ESMO. However, with immunotherapy now integrated into first-line treatment, the contemporary role of LRRT and the definition of patients most likely to benefit from it are uncertain and necessitate further exploration. Methods: This meta-analysis was conducted in accordance with PRISMA guidelines. A comprehensive search was conducted in electronic databases including PubMed, Cochrane Library, and Web of Science from their inception to December 31, 2025, to identify eligible studies comparing immunochemotherapy with or without LRRT in dmNPC. The primary outcomes were PFS and OS. Meta-analysis was performed using OnlineMeta V1.1. Results: A total of six clinical trials were rated as high-quality and included in this meta-analysis. Our meta-analysis results showed that the palliative immunochemotherapy (PICT) plus LRRT group achieved significantly longer PFS (HRs: 0.560, 95%CIs: 0.431-0.727) and OS (HRs: 0.502, 95%CIs: 0.289-0.869) than the PICT alone group. Additionally, single-arm meta-analysis results demonstrated that the 1-year, 2-year, and 3-year PFS rates (with 95% CIs) in the PICT plus LRRT group were 80.5% (76.3%-84.2%), 56.3% (53.7%-58.9%), and 37.6% (28.6%-47.5%), compared with 62.7% (56.2%-68.8%), 26.3% (16.8%-38.7%), and 7.6% (2.4%-21.6%) in the PICT group. Regarding OS, the 1-year, 2-year, and 3-year rates (with 95% CIs) were 97.1% (95.3%-98.2%), 84.2% (72.3%-91.6%), and 76.0% (47.4%-91.7%) in the PICT plus LRRT group, whereas those in the PICT group were 76.9% (33.5%-95.7%), 55.8% (13.7%-90.9%), and 39.7% (1.7%-88.4%). Sensitivity analysis confirmed the stability of the results, and no significant publication bias was detected. Subgroup analyses indicated that dmNPC patients achieved greater PFS benefit from LRRT when they had partial or complete response to PICT (HRs: 0.509, 95%CIs: 0.368-0.704), undetectable post-treatment EBV DNA (HRs: 0.541, 95%CIs: 0.378-0.774), or oligometastatic disease (HRs: 0.349, 95%CIs: 0.193-0.634). Conclusions: In the immunotherapy era, LRRT combined with PICT confers significant and durable survival benefits for dmNPC patients, with pronounced efficacy among those achieving PR/CR to PICT, harboring undetectable post-treatment EBV DNA, or presenting with oligometastatic disease.