Clinicopathological characteristics and prognostic factors of pulmonary large cell neuroendocrine carcinoma: A large population-based analysis

Abstract

Background: The study was conducted to compare the clinicopathological characteristics, survival outcomes, and metastatic patterns between pulmonary large cell neuroendocrine carcinoma (LCNEC) and other non-small cell lung cancer (ONSCLC), and to identify the prognostic factors of LCNEC.

Methods: Data of patients diagnosed with LCNEC and ONSCLC from 2004 to 2014 were obtained from the Surveillance, Epidemiology, and End Results dataset. Pearson's chi-square tests were used to compare differences in clinicopathological characteristics. The Kaplan-Meier method was used for survival analysis. A propensity score was used for matching and a Cox proportional hazards model was used for multivariate and subgroup analyses.

Results: A total of 2368 LCNEC cases and 231 672 ONSCLC cases were identified. LCNEC incidence increased slightly over time. Except for marital status, LCNEC patients had obviously different biological features to ONSCLC patients. Survival analysis showed that LCNEC had poorer outcomes than ONSCLC. Multivariate analysis revealed that female gender, black race, surgery, radiation, and chemotherapy were protective factors for LCNEC. Matched subgroup analysis further demonstrated that most subgroup factors favored ONSCLC, especially in early stage. Early-stage LCNEC patients had a higher risk of lung cancer-specific death than early-stage ONSCLC patients. Moreover, metastatic patterns were different between LCNEC and ONSCLC. LCNEC patients with isolated liver metastasis or combined invasion to other organs had poorer survival rates.

Conclusions: LCNEC has totally different clinicopathological characteristics and metastatic patterns to ONSCLC. LCNEC also has poorer survival outcomes, primarily because of isolated liver metastasis or combined invasion to other organs. Most subgroup factors are adverse factors for LCNEC.

Keywords: Clinicopathological characteristic; SEER; metastasis; prognostic factor; pulmonary large cell neuroendocrine carcinoma.

Figure 1

A flowchart of patient selection and study design. ADC, adenocarcinoma; ASC, adenosquamous carcinoma; ICD‐O‐3, International Classification of Diseases for Oncology, 3rd Edition; LCC, large cell carcinoma; LCNEC, large cell neuroendocrine carcinoma; NSCLC, non‐small cell lung cancer; ONSCLC, other non‐small cell lung cancer; PSC, pulmonary sarcomatoid carcinoma; SCC, squamous cell carcinoma; SEER, the Surveillance, Epidemiology, and End Results dataset.

Figure 2

Kaplan–Meier curves for survival outcomes: (a) lung cancer‐specific survival (LCSS) and (b) overall survival (OS). CI, confidence interval; LCNEC, large cell neuroendocrine carcinoma; m, median; ONSCLC, other non‐small cell lung cancer.

Figure 3

Kaplan–Meier curves for matched groups’ survival outcomes and forest plot of hazard ratios (HRs) for lung cancer‐specific survival (LCSS). Survival curves of (a) LCSS and (b) overall survival (OS) between matched groups. (c) Forest plot of HRs for large cell neuroendocrine carcinoma (LCNEC) versus matched other non‐small cell lung cancer (ONSCLC) in subgroup analysis. The circle and line segments represent the HRs and 95% confidence intervals (CIs) of each subgroup. HR > 1.000 indicates a higher risk of LCS death in patients with LCNEC.

Figure 4

Metastasis distribution and survival analysis for lung cancer‐specific survival (LCSS). (a) Lymph node and distant metastasis rates. () Lymph node metastasis and () Distant metastasis. (b) Isolated‐site metastatic rates. () Bone, () Brain, () Liver, and () Lung. (c) Two‐site metastatic rates. () Bone + Liver, () Bone + Brain, () Bone + Lung, () Brain + Liver, () Brain + Lung, and () Liver + Lung. (d) Three and four‐site metastatic rates. () Bone + Brain + Liver, () Bone + Brain + Lung, () Bone + Liver + Lung, () Brain + Liver + Lung, () Bone + Brain + Liver + Lung. (e) Survival curves for LCSS of large cell neuroendocrine carcinoma (LCNEC). () Bone, () Brain, () Liver, () Lung, and () MO and (f) other non‐small cell lung cancer (ONSCLC) with single organ and multiple organ (MO) metastases. () Bone, () Brain, () Liver, () Lung, and () MO.