Abstract

Background and ObjectivesThis study aims to conduct an updated systematic analysis of patients with pulmonary large cell neuroendocrine carcinoma (PLCNC) in recent decades, concerning incidence and mortality trends, demographics, treatments, survival and death causes.MethodsPatients who were diagnosed with PLCNC at the Peking Union Medical College Hospital (PUMCH) between 2000 to 2020 were retrospectively analyzed. The population-based Surveillance, Epidemiology, and End Results (SEER) database were also retrieved. Frequencies and average annual age-adjusted rates (AAR) of PLCNC patients were calculated and analyzed by Joint-point regression. Univariate and multivariate Cox regression were used for identifying prognostic factors. Predictive nomograms for overall survival (OS) and cancer-specific survival (CSS) were developed and then validated by calculating C-index values and drawing calibration curves. Survival curves were plotted using the Kaplan-Meier method and compared by log-rank test. Causes of death were also analyzed by time latency.ResultsA total of 56 PLCNC patients of the PUMCH cohort were included. Additionally, the PLCNC patients in the SEER database were also identified from different subsets. The AAR from 2001 to 2017 were 3.21 (95%CI: 3.12-3.30) per million. Its incidence and mortality rates in PLCNC patients increased at first but seemed to decline in recent years. Besides TNM stage and treatments, older age and male gender were independently associated with poorer survival, while marital status only affected CSS other than OS. The nomograms for OS and CSS presented great predictive ability and calibration performance. Surgery gave significantly more survival benefits to PLCNC patients, and chemotherapy might add survival benefits to stage II-IV. However, radiation therapy seemed to only improve stage III patients’ survival.ConclusionsThis study supported some previous studies in terms of incidence, survival, and treatment options. The mortality rates seemed to decline recently, after an earlier increase. Among PLCNC patients, most of the deaths occurred within the first five years, while other non-PLCNC diseases increased after that. Thus, careful management and follow-up of other comorbidities are of equal importance. Our study may partly solve the dilemma caused by PLCNC’s rarity and inspire more insights in future researches.

Highlights

  • Lung cancer remains one of the most lethal cancers worldwide and causes countless deaths

  • The diagnosis of Pulmonary large cell neuroendocrine carcinoma (PLCNC) was confirmed by histology from aspiration biopsy or bronchoscopy or surgical specimen, which fulfilled the following criteria: 1) neuroendocrine morphology; 2) high ratio of cell division; 3) necrosis; 4) cytological characteristics of non-small cell lung cancer (NSCLC); 5) immunohistochemistry results: at least one positive biomarker of synaptophysin (Syn), chromogranin A and CD56, or neuroendocrine granules could be found under the electron microscope

  • PLCNC was classified as NSCLC subtypes in the latest version of WHO Classification, it presented genetic and clinical characteristics similar to small cell lung cancer (SCLC)

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Summary

Introduction

Lung cancer remains one of the most lethal cancers worldwide and causes countless deaths. Pulmonary large cell neuroendocrine carcinoma (PLCNC), one special rare subtype of non-small cell lung cancer (NSCLC), accounts for approximately 3% of pulmonary carcinomas throughout America [1]. Demonstrating differences from other NSCLC subtypes, such as lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), PLCNC demonstrated disappointing survival outcomes as small cell lung cancer (SCLC) [1, 2], both of which were classified as pulmonary neuroendocrine neoplasms in the 2015 World Health Organization tumor classification [3]. Systematically analyzing PLCNC patients could provide reference values for understanding the rare disease. This study aims to conduct an updated systematic analysis of patients with pulmonary large cell neuroendocrine carcinoma (PLCNC) in recent decades, concerning incidence and mortality trends, demographics, treatments, survival and death causes

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