Smoking adversely affects survival of metastatic lung carcinoid patients: analysis of a large international audit and prognostic models for metastasis-free survival and overall survival.

Introduction: Among neuroendocrine lung cancers, lung carcinoids (LC, further divided into typical [TC] and atypical [AC]) are rare, representing only the 2% of all bronchopulmonary malignancies, and lack prognostic classification and stratification.

Methods: We audited two international cohorts of patients with a confirmed diagnosis of LC for prognostic analysis. We used data from The Christie Hospital (Manchester, UK; N=282) and validated our findings using the cohort of Vall d'Hebron Hospital patients (Barcelona, Spain, N=80). We analysed patient data to identify a prognostic model for metastasis-free survival (MFS) and stage IV overall survival (OS).

Results: Serum lactic dehydrogenase (LDH) concentration, stage, gender and tumour Ki-67% were significant at multivariable analysis (stratified for stage) for MFS after surgery (C-index=0.76, P<0.001), while histological subtype (TC vs AC) and other clinical variables were not. Independent prognostic factors for OS from onset of metastases included smoking history, along with known factors (patient age, proliferation index, FDG PET maximum SUV). The model C-index was 0.77 (P<0.001), with good concordance when applied to the external validation from Vall d'Hebron (C-index=0.94). Previously undescribed, patients with smoking history lived shorter (median OS=34 months vs not reached, P<0.0001), and the median OS could be shorter in current smokers (26.2 months) compared to ex-smokers (35.3 months).

Conclusion: We provide a novel prognostic tool to estimate patient risk, clinical trial stratification and assist clinical decisions in the rarest lung tumours. We also describe for the first time that smoking history is an independent prognostic factor for OS in stage IV.