Large-cell neuroendocrine carcinoma (LCNC) is a rare tumour characterized by aggressive biological behaviour and poor prognosis. Due to its rarity and the lack of randomized clinical trials, the best treatment is still under debate. Some recent reports indicate that adjuvant chemotherapy (CT) may have a beneficial effect on survival. Our goal was to evaluate this finding using a large series of patients with neuroendocrine tumours obtained from the European Society of Thoracic Surgeons database.

Data for 400 patients with LCNC operated on in 14 thoracic surgery institutions worldwide between 1992 and 2014 were collected retrospectively. Overall survival was the primary endpoint; we used a multivariable Cox regression model to evaluate which clinical variables may influence patient outcomes; we also focused on the possible prognostic role of adjuvant CT. A propensity score (PS) analysis using the inverse probability of treatment weighting was also carried out.

The 3- and 5-year survival rates were 54.1% and 45%, respectively. With the multivariable model, we found that increasing age, Eastern Cooperative Oncology Group Performance Status ≥2 and advanced TNM stage were indicators of poor prognosis. Weak evidence of a higher overall survival in patients receiving adjuvant CT (adjusted hazard ratio 0.73; 95% confidence interval: 0.56-0.96, P  = 0.022) was observed.

A trend towards benefit from adjuvant CT has been observed in patients with LCNC. Although surgical procedures remain the mainstay of curative options, combination with other treatments (e.g. neoadjuvant CT/radiotherapy) should be evaluated by future studies.