# Outcomes for Sinonasal Undifferentiated Carcinoma (SNUC): An International Multi-Center Retrospective Cohort Study

## TL;DR

This study analyzed 485 cases of a rare and aggressive nasal cancer to identify factors affecting patient survival and treatment outcomes.

## Contribution

The study presents the largest multi-center cohort of SNUC, identifying new independent risk factors for poor survival.

## Key findings

- Orbital involvement and distant metastases were independently linked to worse survival outcomes.
- Traditional staging methods were less predictive of survival in SNUC patients.
- Advanced age and higher T-stage were also associated with poorer outcomes.

## Abstract

Sinonasal undifferentiated carcinoma (SNUC) is a very rare and aggressive cancer that arises from the nasal cavity and paranasal sinuses. Due to its rarity, there are no established standards of treatment. Patients often present with a disease that has advanced into adjacent organs such as the eye and the brain, as well as distant spread into organs such as the liver or lung. This study collected information from 485 patients from multiple countries across three continents to examine treatment paradigms in several global centers of excellence, studying factors that may influence patient survival. This study found that involvement of the orbit and the presence of distant spread were associated with worse outcomes, and found that traditional tumor classification and staging measures were less predictive. These findings provide valuable insights into the need for redefining a staging system that may more accurately prognosticate and stratify treatment escalation strategies.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.