Multi-institutional, International Evaluation of Practice Patterns and Outcomes for Recurrent and Metastatic Sinonasal Undifferentiated Carcinoma

Introduction: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive tumor of the sinonasal cavity and skull base. Much of the literature is limited to small case series centered on primary SNUC management, and as such, our understanding of practice patterns and outcomes for recurrent or metastatic cases remains undefined. Our objective was to perform the first study to specifically evaluate recurrent and metastatic SNUC to help guide treatment management for these patients.

Methods: Data was collected via a multi-institutional, international retrospective review of patients with documented diagnosis of recurrent or metastatic SNUC since 1983 at six tertiary treatment centers. Analysis of clinical demographics, treatment practices and outcomes was performed.

Results: Of 218 patients diagnosed with SNUC, 97 total patients with established recurrent or metastatic SNUC were identified, with a median [IQR] age of 52.1 [40.0–64.3] years at the time of their diagnosis. Of these patients, 15 presented with metastatic disease and 90 developed recurrence of their tumor following their initial treatment.

Patients with metastatic disease presented initially with disease localized to their ethmoid sinuses (6/13, 46.2%) and nasal cavity (3/13, 23.1%). This cohort demonstrated a 1-year survival rate [95% CI] of 33.3% [10.8–100%] ([Fig. 1]). Management was widely variable, with numerous regimens involving surgery, chemotherapy, and/or radiation observed across this patient population.

Recurrence was primarily observed in patients after treatment of primary disease in their nasal cavity (33/90, 36.7%), and ethmoid sinuses (22/90, 24.4%). The majority of patients with recurrence had previously been treated with chemoradiation alone (21/81, 25.9%), surgery followed by chemoradiation (14/81, 17.3%), or chemotherapy followed by chemoradiation (13/81, 16.0%). Their recurrent tumor was primarily treated with chemoradiation (15/73, 20.5%), chemotherapy alone (12/73, 16.4%), or surgery alone (11/73, 15.1%). Surgery was involved in some capacity for treating recurrence in 31/73 patients (42.5%). 1- and 5-year survival rates for this population were 45.7% [31.9–65.6%] and 8.6% [2.9–25.3%], respectively ([Fig. 2]). A multivariable cox proportional hazards regression analysis yielded no significant associations between disease specific survival for recurrent disease and various clinical and tumor characteristics including age, sex, orbital involvement, dural involvement, and primary tumor site.

Discussion: To our knowledge, this is the first study addressing metastatic and recurrent SNUC and included a very large number of patients for this rare population. Survival analysis of this dataset did not suggest any predictive characteristics associated with the prognosis of recurrent or metastatic SNUC, highlighting the degree of patient heterogeneity that exists in the presentation of this disease. A 1-year survival rate of 33.3% and 5-year survival rate of 8.6% for metastatic and recurrent disease, respectively, demonstrates the necessity for further evaluation of our current approaches to improve outcomes. However, the large variability across both patient characteristics and treatment modalities emphasizes the challenges in standardizing care for patients with recurrent or metastatic SNUC.

Fig. 1

Fig. 2