Differentiation and stage as independent predictors of survival in laryngeal neuroendocrine carcinoma: A SEER analysis.

Abstract

e18149 Background: Laryngeal neuroendocrine carcinoma (LNEC) is rare and biologically heterogeneous. The independent prognostic roles of tumor differentiation and stage remain incompletely defined. Methods: Patients diagnosed with LNEC (2000–2022) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated using a Kaplan–Meier analysis. Tumor differentiation (Diff) was harmonized across SEER grade fields: legacy Grade Recode (through 2017) was used when available; otherwise, Grade Clinical/Pathological (2018+) codes (1=well, 2=moderate, 3=poor, 4=undifferentiated) defined Diff. Multivariable Cox regression adjusted for stage, Diff, age, and sex. Cases with missing survival time, stage, or Diff were excluded (n=97). Results: The cohort included 157 patients (median age 63 years; 63% male). Diff was well in 4%, moderate in 29%, poor in 34%, and undifferentiated in 12% of patients. At diagnosis, 22% of patients had localized, 27% had regional, and 28% had distant disease. Treatments included surgery in 31%, chemotherapy in 42%, and adjuvant radiation in 13% of patients. Median OS differed significantly by Diff, ranging from 52.5 months (mo) for well, 90 mo for moderate, 12 mo for poor, and 17 mo for undifferentiated (p<0.001). Five-year OS was 50%, 58%, 23%, and 37%, respectively, with a similar gradient for CSS (p=0.001). Survival remained differentiation-associated within surgical (p=0.004) and chemotherapeutic subgroups (p<0.001). Median OS by stage was 96 mo for localized disease, 30 mo for regional nodes only, 8.5–7.5 mo for regional direct extension ± nodes, and 11 mo for distant disease. On multivariable analysis, stage and differentiation—driven primarily by poorly differentiated tumors—were independently associated with OS. Conclusions: Both tumor differentiation and stage independently predicted survival in LNEC, indicating that tumor biology and anatomic extent each contribute to prognosis. Outcomes remain suboptimal in poorly differentiated and advanced-stage LNEC, underscoring the need for treatment optimization and clinical trial development. Variable HR (95% CI) p Differentiation (Diff) Moderate vs Well 1.76 (0.49–6.31) 0.39 Poor vs Well 6.11 (1.63–22.93) 0.007 Undifferentiated vs Well 2.28 (0.60–8.76) 0.23 Stage Nodes only vs Localized 2.21 (1.14–4.38) 0.023 Direct extension only vs Localized 14.04 (2.44–80.97) 0.003 Direct + nodes vs Localized 7.49 (3.19–17.63) <0.001 Distant vs Localized 3.34 (1.63–6.83) 0.001 Male vs Female 2.28 (1.34–3.89) 0.002