Survival and treatment selection in NUT carcinoma: a population-based study and propensity score-matched comparison with poorly differentiated head and neck squamous cell carcinoma.

Background: NUT carcinoma (NC) is a rare and highly aggressive malignancy that can arise in the head and neck, thorax, and other organs. Large population-based studies remain limited, and survival comparisons with poorly differentiated head and neck squamous cell carcinoma (HNSCC), a common histologic mimic, have not been adequately controlled for baseline clinical imbalance. This study aimed to characterize survival and prognostic factors in NC and to compare survival between head and neck NC and poorly differentiated HNSCC after balancing baseline characteristics. Methods: In this retrospective population-based cohort study, primary NC diagnosed from 2018 to 2023 was identified from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) was analyzed with Kaplan-Meier and Cox models. Landmark analyses and time-dependent Cox modeling assessed treatment-timing bias. Head and neck NC was compared with poorly differentiated HNSCC using propensity score matching (PSM). Results: There were 91 NC patients included, 39 with head and neck disease. After excluding cases with missing matching covariates, 36 head and neck NC cases and 7,633 HNSCC comparators were included in propensity-score analyses. In NC, 61 patients (67.0%) died and median OS was 8 months. Older age, non-head and neck site, distant stage, M1 disease, and larger tumor size were associated with worse OS. In conventional multivariable Cox models, surgery, chemotherapy, and radiotherapy were associated with improved OS. After incorporating landmark and time-dependent approaches, chemotherapy was no longer robust, whereas radiotherapy, surgery, overall treatment status, and stage remained relevant depending on the analytic framework. Before matching, head and neck NC had worse OS than HNSCC; this association was attenuated after balancing measured clinical variables. Conclusions: NC has poor population-based survival, with stage and treatment status as major survival-related factors. The observed survival disadvantage of head and neck NC relative to poorly differentiated HNSCC was attenuated after matching for measured clinical characteristics, but the imprecision of the matched estimates precludes conclusions of prognostic equivalence or exclusion of a clinically important difference.