The impact of stage and cell type on the prognosis of pulmonary neuroendocrine tumors

Objective: In pulmonary neuroendocrine tumors the realization that the extent of nodal disease is related to cell type has led to a controversy as to which is the dominant prognostic factor, stage or morphology. To clarify this relationship, we studied patients treated at our institution over a 23-year period. Methods: This is a historical cohort study of patients with confirmed pulmonary neuroendocrine tumors who underwent lung resection from 1980 through 2003. Survivors were contacted by telephone, and recurrences were confirmed by means of histopathology. Cox proportional hazards regression was used to ascertain the joint influence of several risk factors on survival. Results: The mean age of the cohort was 54 years (standard deviation, 15 years), and 100 (57%) were men. The cell types for the 177 eligible patients were typical carcinoid in 89 (50%), atypical carcinoid in 15 (8%), large cell in 22 (13%), and small cell in 51 (29%). The median time to follow-up was 7 years (first to third quartile, 2-12 years), and overall 5- and 10-year survivals were 86% (79%-90%) and 81% (74%-87%), respectively. The univariable predictors of survival were age (P = .001), nodal stage (P = .01), and cell type (P < .001). In the final multivariable model only age (P = .04) and cell type (P < .001) remained as independent predictors. The hazard of death among patients with large cell or small cell lung cancer was highest in the first year and a half after diagnosis, reducing drastically thereafter. Conclusions: In pulmonary neuroendocrine tumors cell type is the predominant determinant of survival. The survival of patients with each cell type is sufficiently diverse to warrant different management strategies. Conservative resection is feasible for typical carcinoids, but the effects of adjuvant chemotherapy need to be evaluated for the other subgroups.