New Prognostic Frontiers for Lung Neuroendocrine Tumors

Background: Well-differentiated neuroendocrine tumors of the lung (Lung NET) are classified as typical (TC) and atypical (AC) carcinoids, on the basis of mitotic count and presence of necrosis. However, the identification of prognostic factors, other than TNM stage and histopathological diagnosis of AC versus TC, are still lacking. Methods: We assessed the association of clinical and pathological data with survival in a multicenter retrospective series of 200 surgically resected lung NET from 8 Italian & 1 Spanish Institutions. Patients data were collected and analysed by SPSS program. Results: The study population presented a median age of 60 years (13-86), 40.0% presented a male gender, 31.5% were smokers, 31.0% AC, 40.5% left-sided tumors, 36.5% with a peripheral location. I&II TNM stages at diagnosis were present in 84.5% of cases, with 25% nodal positive status. Mitotic count 2/10 HPF in 31%, necrosis in 17.5%, Ki67 >20% in 8 patients (4%). The population had a median OS of 49 months (0.6-323), and a median PFS of 36.0 months (0.5-323). At Cox univariate regression model, male gender (p¼0.0001, p¼0.001), left side (p¼0.001, p¼0.015), nodal positive status (p¼0.0001, p¼0.0001), advanced TNM stage (p<0.0001, p<0.0001), mitotic count 2/10 HPF (p¼0.001,p¼0.031), Ki67 >20% (p¼0.017, p¼0.001), presence of necrosis (p¼0.001, p¼0.04), and AC histotype (p¼0.0001, p¼0.006), correlated with shorter PFS and OS, respectively. Tumoral peripheral location (p¼0.038) correlated with shorter OS. At Cox multivariate regression analysis, gender (male vs female) (p¼0.0057), tumor side (left vs right) (p¼0.0118), advanced stage (p¼0.0206), a Ki67 >20% and/or a mitotic count >10/10 HPF (p¼0.0109), and the presence of necrosis (p¼0.0010) were confirmed as independent prognostic factors in terms of PFS. Gender (male vs female) (p¼0.0127), tumor side (left vs right) (p¼0.0669) and advanced stage (p¼0.0208) were independent negative prognostic factors for OS. Conclusions: This study confirm the prognostic relevance of TNM stage and of the diagnosis of AC, to stratify NET patients. Additionally, our analysis suggests a potential prognostic value for new clinical and pathological features, as male gender, left-sided primary tumor and high proliferation index