Treatment of Locally Advanced Layngohypopharyngeal Cancers: A Network Meta‐Analysis

OBJECTIVE: To compare the efficacy of non-surgical organ-preservation strategies for locally advanced or resectable laryngeal and hypopharyngeal squamous cell carcinoma (SCC). DATA SOURCES: Randomized controlled trials (RCTs) published through June 30, 2025, identified via systematic database and trial-registry searches and reference screening. REVIEW METHODS: We performed a systematic review and Bayesian random-effects network meta-analysis of RCTs enrolling adults with locally advanced/resectable laryngeal/hypopharyngeal SCC. Treatments included surgery plus postoperative radiotherapy (RT), RT alone, concurrent cisplatin-based chemoradiotherapy (CTRT), induction chemotherapy followed by RT/CTRT, altered-fractionation RT, dose-modified CTRT, and RT ± cetuximab. Effect estimates were synthesized as hazard ratios (HRs) and odds ratios (ORs). Treatments were ranked using surface under the cumulative ranking curve (SUCRA). RESULTS: Fifteen RCTs (n = 4395; 13 strategies) were included. For laryngeal preservation, cisplatin-based CTRT ranked highest (SUCRA 0.73), followed by induction TPF → RT (0.72) and RT + cetuximab (0.61). All non-surgical strategies outperformed surgery plus postoperative RT for laryngeal preservation (HR 0.34; 95% CI, 0.20-0.58). For overall survival, induction PF → RT showed the highest probability of benefit (SUCRA 0.68), with overlapping credible intervals across leading regimens. For locoregional control, induction TPF → RT ranked best (SUCRA 0.94). Sensitivity analyses supported robustness. CONCLUSION: Concurrent cisplatin-based CTRT remains the most consistent organ-preservation strategy. Induction PF → RT may offer modest overall survival benefit, whereas sequential TPF → RT appears superior for locoregional control. Treatment should be individualized by comorbidity, functional goals, and institutional expertise; head-to-head trials and incorporation of immunotherapy/targeted agents are needed. LEVEL OF EVIDENCE: N/A.