The introduction of chemoradiation for advanced laryngeal cancer led to a major paradigm shift in treatment as an alternative to laryngectomy. Despite widespread adoption, survival rates have not improved and the original premise of matching neoadjuvant chemotherapy tumor response to determine subsequent treatment has not been followed. A unique approach incorporating a single cycle of neoadjuvant chemotherapy to select patients with advanced disease for either laryngectomy or concurrent chemoradiation was studied to determine if improved survival could be achieved. Design From 2002–2012, we treated an unselected cohort of 247 patients with laryngeal cancer in an academic institution. Interventions Limited disease patients (n=94) underwent endoscopic resection (n=33; 35%), radiation (n=50; 53%) or chemoradiation for deeply invasive T2 lesions (n=11; 12%). For advanced disease (n=153), neoadjuvant chemotherapy for treatment selection (n=71; 46%), concurrent chemoradiation (n=50; 33%) or primary surgery (n=32; 21%) was recommended. Outcomes Propensity for treatment selection in advanced patients was modeled using logistic regression. Overall (OS) and disease specific survival (DSS) were analyzed with Cox proportional hazards models stratified by propensity score. Median follow was 48 months. Results Five-year OS and DSS was 75% (95% C.I. 68–81%) and 83% (77–88%), respectively for the entire cohort. DSS was 92% (83–97%) for patients with Stage I, II and 78% (69–84%) for patients with Stage III, IV disease. For advanced disease patients, 5-year OS (and DSS) ranged from 78% (91%) for surgery to 76% (79%) for neoadjuvant bioselection and 61% (66%) for primary chemoradiation. Propensity-adjusted multivariable Cox models controlling for known prognostic factors showed DSS was significantly improved in the neoadjuvant group compared to definitive chemoradiation [Hazard ratio 0.48, 95%CI: (0.29, 0.80), p=0.005]. DSS for the definitive surgery group was significantly better compared to the neoadjuvant bioselection group, [Hazard ratio 0.34, 95%CI: (0.14, 0.82), p=0.02]. Larynx preservation was achieved in 65% of advanced patients. Conclusions Exceptional survival rates were achieved with a bioselective treatment approach utilizing a single cycle of neoadjuvant chemotherapy. Excellent survival rates were also achieved in patients selected for primary surgery and both were better than with concurrent chemoradiation suggesting that the optimal individualized treatment approach for patients with advanced laryngeal cancer has not yet been defined.

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