Objective Sinonasal undifferentiated carcinoma (SNUC) is a locally aggressive undifferentiated
               neuroendocrine tumor originating from nasal cavity or paranasal sinus epithelium.
               The value of adding induction chemotherapy to definitive treatment is unknown. This
               study aimed to assess the role of induction chemotherapy followed by concurrent chemoradiotherapy
               (CRT) compared with surgery for SNUC.
            
               Methods This study investigated 97 patients with stage II (N = 8), III (N = 13), and IV (n = 76) SNUC treated between 1995 and 2016 in MD Anderson Cancer Center. SNUC patients
               were treated with three cycles of cisplatin (60−80 mg/m2) and etoposide (100−120 mg/m2) every 21 days. The primary endpoint was disease-specific survival. Our secondary
               outpoints were overall and disease-free survival and organ (i.e., palate, eye, and
               brain) preservation.
            
               Results The median follow-up was 28 months (range: 2−281 months). Induction chemotherapy
               was administered to 69 (70%) patients. Of those, 41 (60%) had subsequent concurrent
               chemoradiotherapy and 11(16%) had surgery. Surgery (n = 20) or CRT (n = 8) were the primary therapy in 28 (30%) patients. The 5-year overall survival (OS)
               rates were 61 and 56% in the induction chemotherapy and surgery/CRT treatment groups,
               respectively (p = 0.52). The 5-year disease-specific survival (DSS) rates were 61 and 59% in induction
               chemotherapy and surgery/CRT treatment groups, respectively (p = 0.35). The 5-year disease-free survival (DFS) did not differ significantly between
               treatment groups (p = 0.76). Local recurrence was the most common form of treatment failure and occurred
               in 23 (24%) patients. Distant metastasis, most commonly to the lungs, occurred in
               20 (n = 21%) patients. The 5-year distant metastasis rates were similar in patients treated
               systemically with induction chemotherapy (73%) or surgery/CRT (73%, p = 0.88). The rate of organ preservation was 91 and 89% in the induction chemotherapy
               and surgery/RT treatment groups, respectively (p = 0.79). Multivariate analysis revealed that the patient's age and extent of disease
               were independent predictors of 5-year disease-specific survival.
            
               Conclusion In patients with SNUC, adding induction chemotherapy is noninferior to primary surgical
               resection or concurrent administration of chemoradiotherapy for disease-specific survival,
               local control, and distant metastasis free survival and organ preservation rates.
               Future studies are needed to compare induction chemotherapy followed by concurrent
               chemoradiotherapy and primary concurrent chemoradiotherapy.