Real‐World Insights Into cN3 Larynx and Hypopharynx Cancer: Treatment Modalities, Long‐Term Outcomes, and Prognostic Factors

ABSTRACT Objectives cN3 larynx and hypopharynx cancer is rare with a poor prognosis. This study evaluates treatment approaches, effectiveness, and prognosis for these patients in real‐world settings. It aims to offer targeted and practical clinical guidance to enhance their treatment results and quality of life. Methods This retrospective cohort study (2014–2021) included 192 cN3 larynx and hypopharynx cancer patients from Eye & ENT Hospital of Fudan University. We collected detailed information on demographics, tumor characteristics, and treatment outcomes. The study focused on overall survival (OS), cancer‐specific survival (CSS), and disease‐free survival (DFS), using Kaplan–Meier and Cox regression analyses for independent prognostic analysis. Results This study encompassed 192 cN3 larynx and hypopharynx cancer patients, revealing a five‐year overall survival rate of 40.60%. Treatment modalities analyzed included Surgery + CRT, ICT + Surgery + CRT, ICT + CRT, Surgery alone, and CRT alone. Patients receiving surgery followed by CRT demonstrated the most favorable prognosis ( p < 0.0001) and the longest DFS ( p < 0.0001), while those undergoing monotherapy had the poorest outcomes. Induction chemotherapy (ICT) achieved a 70% primary tumor response rate and a 48% neck lesion response rate, with patients showing a response to ICT exhibiting superior OS, CSS, and distant metastasis rate (DMR) ( p < 0.05). Pathological type and primary tumor surgery were identified as independent prognostic factors for cN3 larynx and hypopharynx cancer. Conclusion This study shows that combined treatments, especially surgery followed by chemoradiotherapy, improve survival and prognosis for cN3 larynx and hypopharynx cancer patients. It highlights the importance of tailored treatments and notes better outcomes for those responding to ICT. Level of Evidence 3.