Defining the role of adjuvant therapy for early-stage large cell neuroendocrine carcinoma.

Introduction: Large cell neuroendocrine carcinoma is a rare, high-grade neuroendocrine tumor. The mainstay of treatment for early, node-negative disease is surgical resection, and optimal adjuvant treatment strategies are not well defined.

Methods: Patients with early, node-negative large cell neuroendocrine carcinoma were identified in the National Cancer Database from 2004 to 2014. Patient, tumor, treatment, and hospital characteristics were examined. Survival differences in patients receiving adjuvant chemotherapy (AC) were evaluated using Kaplan-Meier curves, and adjusted multivariate Cox models were constructed. A conditional landmark analysis was used to address immortal time bias. T-stage-specific propensity score matching was used to address covariate imbalances between groups.

Results: One thousand seven hundred seventy patients were identified, of whom 463 (26.2%) received AC. Patients receiving AC were younger, less comorbid, and more likely to have T2 tumors. AC was associated with significantly longer survival, which persisted after adjustment in Cox models, for patients overall (5-year overall survival, 59.2% vs 45.3%; hazard ratio, 0.69; 95% confidence interval, 0.58-0.82; P < .0001), T2 tumors (overall survival, 59.8% vs 42.1%; hazard ratio, 0.63; 95% confidence interval, 0.50-0.81; P < .0001), and tumors 2 to 3 cm (overall survival, 60.0% vs 42.6%; hazard ratio, 0.64; 95% confidence interval, 0.46-0.8; P = .002), but not tumors smaller than 2 cm. Adjuvant chest radiotherapy was not associated with longer survival. Sublobar resection was associated with worse overall survival compared with lobectomy (hazard ratio, 1.40; 95% confidence interval, 1.20-1.64; P < .0001). Propensity score matching confirmed these findings, but the association with survival for tumors 2 to 3 cm in size was not significant.

Conclusions: In this national study of early-stage large cell neuroendocrine carcinoma, AC was associated with significantly longer survival for tumors larger than 3 cm, and possibly for tumors 2 to 3 cm. Adjuvant radiation was not associated with prolonged survival.