Local Consolidative Radiotherapy Combined With Immunochemotherapy for De Novo Metastatic Nasopharyngeal Carcinoma: A Meta‐Analysis

ABSTRACT Background Immunochemotherapy is the standard care of newly diagnosed metastatic nasopharyngeal carcinoma (NPC). Limited trials with small sample sizes reported the potential benefit of delivering radiotherapy in these patients. The purpose of our systematic review and meta‐analysis was to examine the efficacy and toxicity of local consolidative radiotherapy when combined with immunochemotherapy as the first‐line treatment in newly diagnosed metastatic NPC, providing a reference for clinicians to make the best choice in clinical practice. Methods A comprehensive search was conducted in PubMed, Embase, Cochrane Library, Medline, and CNKI to identify published literature between January 1, 2004 and June 30, 2025 to identify potential eligible studies, including patients with pathologically confirmed de novo metastatic NPC treated with radiotherapy and immunochemotherapy. Toxicity rates, progression‐free survival (PFS), and overall survival (OS) for the endpoints of interest were extracted from the articles, and the 95% confidence intervals (CIs) were estimated. The systematic review and meta‐analysis were conducted in accordance with the PRISMA 2020 Statement, and the study protocol was prospectively registered in PROSPERO (CRD42024607034). Results Seven studies with a total of 802 patients were analyzed to evaluate the efficacy and toxicity of first‐line local radiotherapy and immunochemotherapy in newly diagnosed metastatic NPC. The results showed that the addition of consolidative radiotherapy to immunochemotherapy significantly improved PFS in de novo metastatic NPC (HR = 0.48 [0.38, 0.60]) using a fixed‐effects model ( I 2 = 44%, p = 0.15). The random‐effects pooled result indicated that consolidative radiotherapy added to immunochemotherapy failed to improve OS (HR = 0.52, 95% CI: 0.18–1.61, I 2 = 59%, p = 0.12). The pooled event rates of toxicities are 62.52% (95% CI: 25.22%–92.73%, I 2 = 97.8%), 63.03% (95% CI: 29.6%–90.6%, I 2 = 97.2%), 57.54% (95% CI: 30.72%–82.15%, I 2 = 95.6%), 21.29% (95% CI: 8.08%–39.37%, I 2 = 91.2%), 7.12% (95% CI: 0.33%–21.55%, I 2 = 87.1%) for mucositis, dermatitis, xerostomia, ear toxicity, and trismus of all grades, respectively. Grade 3–4 mucositis, dermatitis, xerostomia, ear toxicity, and trismus were 9.57% (95% CI: 3.37%–18.49%, I 2 = 79.4%), 3.5% (95% CI: 1.87%–5.63%, I 2 = 19.3%), 0.39% (95% CI: 0.01%–1.29%, I 2 = 37.4%), 1.37% (95% CI: 0.01%–4.95%, I 2 = 69.3%), and 0.26% (95% CI: 0%–1.25%, I 2 = 0%), respectively. Conclusions Local consolidative radiotherapy combined with immunochemotherapy in de novo metastatic NPC may improve PFS, whereas no statistically significant OS benefit was observed. Of note, the OS finding should be interpreted cautiously given the limited studies available for pooled OS analysis. The pooled toxicity rate derived in this systematic review and meta‐analysis can be a guide for clinical decision‐making and patient management.