Prognostic Impact of Large Cell Neuroendocrine Histology in Patients with Pathologic Stage Ia Pulmonary Non-small Cell Carcinoma

Background: Most patients with pathologic stage Ia non-small cell lung carcinoma have a good prognosis, and adjuvant chemotherapy is currently not being used in the management of this stage of the disease. However, if significant negative prognostic factors become evident in patients with pathologic stage Ia non-small cell lung carcinoma, patients with negative prognostic factors should have adjuvant treatment after surgery.

Methods: We analyzed 335 cases of pathologic stage Ia non-small cell lung carcinoma treated between 1988 and 2003 by complete resection. The pathologic stage Ia non-small cell lung carcinomas comprised 259 adenocarcinomas, 65 squamous cell carcinomas, and 11 large cell neuroendocrine carcinomas. The prognostic impact of various clinical variables was investigated by the Cox proportional hazards multivariable regression model.

Results: Univariate analysis showed that large cell neuroendocrine carcinoma histology, old age, large tumor size, male gender, and smoking predicted poorer overall survival. Large cell neuroendocrine carcinoma had a significantly poorer prognosis than other non-small cell carcinomas. Multivariate analysis revealed that large cell neuroendocrine carcinoma was predictive of poorer overall survival (P = .0200, hazard ratio 2.787).

Conclusions: Large cell neuroendocrine histology has a significant adverse prognostic impact on pathologic stage Ia non-small cell carcinoma. Therefore, surgical resection alone represents insufficient treatment for large cell neuroendocrine carcinoma, even for pathologic stage Ia disease.