Histology-dependent survival and treatment benefit in primary tracheal cancer: A population-based analysis.

Abstract

e23386 Background: Primary tracheal cancer is a rare thoracic malignancy representing only 0.1-0.4% of all malignancies. Evidence is largely limited to small institutional series, leaving uncertainty regarding prognostic stratification and optimal treatment across histologic subtypes. We conducted a population-based analysis to evaluate histology-specific treatment patterns and survival outcomes. Methods: We utilized the SEER database to identify adults with primary tracheal cancer (ICD-O-3 C33.9) between 2000 and 2022. Histologies were categorized as squamous cell carcinoma (SCC), adenoid cystic carcinoma (ACC), small cell carcinoma, or other subtypes. Treatments included surgery, radiation therapy, and chemotherapy. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariable Cox proportional hazards models identified factors independently associated with OS. Sensitivity analyses included cancer-specific survival and interaction testing between histology and treatment modality. Results: Among 1,701 patients identified, the median age was 66 years, and 57.7% were male. Histologies included SCC (48.4%), ACC (16.9%), small cell carcinoma (4.4%), and other subtypes (30.3%). At diagnosis, 33.0% had localized disease, 27.1% regional disease, and 11.5% distant disease. Overall, 70.7% received radiation therapy, 27.9% chemotherapy, and approximately 20% underwent surgical resection. Median OS was 22 months, with a 5-year OS of 34.7%. Survival differed significantly by histology (p < 0.001), with a median OS of 130 months for ACC, 13 months for SCC, 7 months for small cell carcinoma, and 28 months for other histologies, demonstrating intermediate survival. In multivariable analysis, SCC (HR 2.49) and small cell carcinoma (HR 3.59) had higher mortality than ACC. Earlier stage was strongly associated with improved survival (localized vs distant: HR 0.38, 95% CI 0.30-0.47; p < 0.001). Surgical resection (HR 0.48, 95% CI 0.41-0.56; p < 0.001) and radiation therapy (HR 0.71, 95% CI 0.63-0.80; p < 0.001) were independently associated with improved OS, whereas chemotherapy was associated with worse survival (HR 1.29, 95% CI 1.15-1.45), consistent with confounding by indication. A significant histology radiation interaction was observed (p = 0.01), suggesting differential benefit across histologic subtypes. Results were consistent in cancer-specific survival analyses. Conclusions: Survival in primary tracheal cancer varies profoundly by histology and stage. ACC demonstrates markedly superior outcomes, and surgical resection, when feasible in appropriately selected individuals, is associated with improved survival. These findings support histology-driven risk stratification and strengthen the importance of referral to specialized centers for histology-informed multimodality care.