Comparison of induction chemotherapy followed by concurrent chemoradiotherapy versus neoadjuvant chemotherapy followed by surgery and (chemo)radiotherapy in locoregionally advanced hypopharyngeal carcinoma: a prospective cohort study.

内容摘要

The optimal strategy for laryngeal preservation in locally advanced hypopharyngeal carcinoma (LAHPC) remains undefined. This prospective observational study compared long-term outcomes between two primary treatment approaches: induction chemotherapy followed by concurrent chemoradiotherapy (IC-CCRT) and neoadjuvant chemotherapy followed by surgery and adjuvant (chemo)radiotherapy (NAC-Sur-RT). From December 2018 to December 2023, 199 patients with LAHPC were prospectively enrolled and treated with either IC-CCRT (n&#x2009;=&#x2009;124) or NAC-Sur-RT (n&#x2009;=&#x2009;75). The primary endpoints were survival with functional larynx (SFL), overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS). Prognostic factors were identified using multivariable Cox regression. In the matched cohort (median follow-up 49&#xa0;months), NAC-Sur-RT was associated with significantly superior 5-year OS (58.3% vs 46.2%; adjusted HR&#x2009;=&#x2009;0.60; 95% CI 0.38-0.95; P&#x2009;=&#x2009;0.031) and DMFS (56.2% vs 41.6%; adjusted HR&#x2009;=&#x2009;0.59; 95% CI 0.38-0.92; P&#x2009;=&#x2009;0.023), and PFS (52.2% vs 37.2%; adjusted HR&#x2009;=&#x2009;0.64; 95% CI 0.42-0.98; P&#x2009;=&#x2009;0.040). Conversely, NAC-Sur-RT was associated with a significantly higher risk of SFL failure (27.0% vs 43.1%; adjusted HR&#x2009;=&#x2009;2.18; 95% CI 1.45-3.27; P&#x2009;<&#x2009;0.001). No significant differences were found in LFFS or LRFFS. Failure pattern analysis indicated more isolated local recurrences with IC-CCRT (15.3% vs 5.3%) but higher regional recurrence with NAC-Sur-RT (1.6% vs 6.7%). Multivariable analysis confirmed NAC-Sur-RT as an independent predictor of improved OS (HR&#x2009;=&#x2009;0.60; P&#x2009;=&#x2009;0.031), PFS (HR&#x2009;=&#x2009;0.64; P&#x2009;=&#x2009;0.040), and DMFS (HR&#x2009;=&#x2009;0.59; P&#x2009;=&#x2009;0.023), but also of worse SFL (HR&#x2009;=&#x2009;2.18; P&#x2009;<&#x2009;0.001). AJCC stage IVB disease independently predicted inferior OS (HR&#x2009;=&#x2009;9.05; 95% CI 1.52-53.81; P&#x2009;=&#x2009;0.015) and DMFS (HR&#x2009;=&#x2009;8.49; 95% CI 1.53-47.23; P&#x2009;=&#x2009;0.015). Additionally, NAC-Sur-RT was associated with significantly higher rates of severe (grade 3-4) toxicities, including laryngeal/esophageal, mucosal, hematologic, and functional adverse events. In this non-randomized prospective comparison, the NAC-Sur-RT strategy was associated with superior survival outcomes (OS, PFS, DMFS) but at the cost of increased severe toxicity and a significantly lower rate of functional larynx preservation. IC-CCRT offers a higher probability of survival with a functional larynx despite a higher risk of local recurrence. Treatment selection should be individualized, balancing survival benefits, functional outcomes, and toxicity profiles. The study was approved by the ethics board of the Chinese PLA General Hospital and registered in the Chinese Clinical Trial Registry (registered number: ChiCTR2000039813).