Comparison of clinicopathologic features and prognosis between surgically resected pulmonary large-cell neuroendocrine carcinoma and small-cell lung cancer

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Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are classified as types of high-grade neuroendocrine carcinoma (HGNEC). The aim of this study was to determine the similarities and differences in clinical features and prognosis between LCNEC and SCLC. Methods: We retrospectively compared the clinical features and prognosis of LCNEC and SCLC, along with well as their two subtypes, including pure LCNEC (P-LCNEC) and combined LCNEC (C-LCNEC) and SCLC combined with LCNEC and SCLC combined with non-LCNEC, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: We included 341 patients with LCNEC and 580 patients with SCLC who underwent surgical treatment. Significant differences in smoking history, primary site, tumor location, pathological (p) N stage, pTNM stage, and visceral pleural invasion (VPI) were observed between LCNEC and SCLC groups (all P values <0.05). The subgroups of LCNEC (P-LCNEC and C-LCNEC) and SCLC (SCLC/LCNEC and SCLC/non-LCNEC) displayed differences in smoking history, primary site, tumor location, pT stage, pN stage, pTNM stage, VPI, adjuvant chemotherapy, and postoperative adjuvant radiotherapy. LCNEC and its subtypes P-LCNEC and C-LCNEC were associated with superior DFS and OS than were SCLC and its subtypes SCLC/LCNEC and SCLC/non-LCNEC (DFS: P=0.008, P=0.001, P=0.049; OS: P=0.005, P=0.005, P=0.006). Compared to patients who did not receive adjuvant chemotherapy, those with stage I SCLC or LCNEC who underwent adjuvant chemotherapy demonstrated a significantly improved DFS (P=0.005 and P=0.048) and OS (P=0.004 and P=0.03). Conclusions: LCNEC and SCLC, as well as their subtypes, have distinct clinical features and survival outcomes. SCLC exhibited more malignant biological behavior and was associated with a worse prognosis compared to LCNEC. Postoperative chemotherapy is recommended for patients with stage I HGNEC.

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