Adjuvant chemotherapy and survival after resection for pulmonary large-cell neuroendocrine carcinoma: a dual-center time-dependent analysis.

BACKGROUND

For patients with resected large-cell neuroendocrine carcinoma, the role of adjuvant chemotherapy remains uncertain, and factors associated with greater benefit are not well defined. This study aimed to evaluate the association between adjuvant chemotherapy and survival outcomes while accounting for treatment timing and to identify clinicopathologic subgroups that may derive greater benefit.

METHODS

This dual-center retrospective study included 185 patients with resected large-cell neuroendocrine carcinoma. To reduce treatment-timing bias, a time-dependent multivariable Cox proportional hazards model was used, in which adjuvant chemotherapy was treated as a time-dependent exposure. Overall survival and disease-free survival were evaluated. Sensitivity analyses, including time-fixed and landmark approaches, were performed to assess the robustness of the findings. Subgroup analyses were conducted in selected clinically relevant strata.

RESULTS

In the primary time-dependent multivariable Cox model, adjuvant chemotherapy was associated with improved overall survival (hazard ratio, 0.54; 95% confidence interval, 0.33-0.88; P=0.01). In contrast, adjuvant chemotherapy was not significantly associated with improved disease-free survival (hazard ratio, 0.88; 95% confidence interval, 0.57-1.38; P=0.59). Subgroup analyses suggested that the overall survival association was more pronounced in clinically higher-risk subgroups, particularly in patients with stage II-III disease (hazard ratio, 0.37; 95% confidence interval, 0.19-0.71; P=0.003) and node-positive disease (hazard ratio, 0.27; 95% confidence interval, 0.12-0.63; P=0.002). Sensitivity analyses showed generally consistent effect directions across different analytic strategies.

CONCLUSIONS

In this dual-center retrospective cohort, postoperative adjuvant chemotherapy was associated with improved overall survival after resection for large-cell neuroendocrine carcinoma, whereas no significant association was observed for disease-free survival. The overall survival association appeared stronger in selected higher-risk subgroups, including patients with stage II-III disease and node-positive disease. Further studies are warranted to better define the patients most likely to benefit from adjuvant chemotherapy.