Survival Outcomes in Sinonasal Poorly Differentiated Squamous Cell Carcinoma

Introduction: Primary sinonasal malignancies are rare with squamous cell carcinoma (SCC) representing the most common type. Histological differentiation of SCC has been shown to determine its biological behavior. Multimodality treatment is often employed in management of these tumors, though there is no consensus on treatment regimen and sequence of therapy. Our goal is to analyze treatment outcomes in poorly differentiated SCC (PDSCC) using a large national database.

Methods: The National Cancer Database (NCDB) was queried for sinonasal invasive SCC, grade 3 (poorly differentiated) from 2004 to 2014. Patient demographics (age, sex, and race), tumor characteristics (TNM stage, primary site, grade, and histological subtype), and treatment characteristics (year, treatment modalities, facility volume, and surgical margin status) were tabulated. Kaplan–Meier (KM) analysis was performed to compare overall survival (OS) between tumor histology subtype as well as primary tumor site. Multivariable Cox’s proportional hazards regression was performed for statistical analysis of treatment regimen on OS.

Results: A total of 1,074 patients were identified. Most patients were white (82%) males (67%) with a median age of 64 years. The maxillary sinus was the most common site (45%) and SCC, NOS the most common subtype (72%). T4 tumors were observed in 50% of patients with most patients treated at high volume facilities (77%) with radiation therapy alone (25.2%) followed by surgical resection with adjuvant radiation (24.4%). Among them, 626 patients underwent surgical resection as part of their treatment and in 63% of these cases, negative margins were obtained. In KM analysis, spindle cell SCC histological subtype was associated with worse OS (median OS: 15.1 months, p = 0.028) as were primary tumors of the maxillary sinus (median OS: 25 months, p < 0.001). In our Cox-PH model, higher T-stage (HR = 1.92, 2.61, and 3.60 for T2, T3 and T4 patients, respectively; p < 0.001) and age (HR = 1.02, p < 0.001) was associated with worse survival. Treatment at a high-volume facility (HR = 0.68, p = 0.01) and those who underwent surgical resection followed by adjuvant radiation (HR = 0.68, p = 0.01) had improved OS. Chemotherapy within the treatment regimen did not confer survival benefit overall (NS). In a model of only surgical patients, surgery plus adjuvant radiation when negative margins were obtained (HR = 0.71, p = 0.09), and surgery plus chemoradiation when positive margins were present (HR = 0.63, p = 0.08) trended toward improved survival.

Conclusion: Sinonasal PDSCC appears to be best treated at high-volume centers with surgical resection plus adjuvant radiation. Chemotherapy may have a role in patients with positive surgical margins along with adjuvant radiation. A prospective, multicenter, randomized controlled trial is necessary to confirm these findings.