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. 2025 Apr 30;17(4):2394-2410.
doi: 10.21037/jtd-2025-345. Epub 2025 Apr 27.

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

Yuke Mao #  1 , Hao Chang #  1 , Lu Wang #  1 , Jinlong Teng  2 , Tianjun Li  1 , Luca Ampollini  3 , Yoshinobu Ichiki  4 , Robert A Ramirez  5 , Hong Liu  1 , Baohui Han  6 , Jing Wang  1 , Yanan Wang  1
Affiliations

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

Yuke Mao et al. J Thorac Dis. .

Abstract

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.

Keywords: Pulmonary high-grade neuroendocrine carcinoma (pulmonary HGNEC); large-cell neuroendocrine carcinoma (LCNEC); pure and combined subtypes; small-cell lung cancer (SCLC).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-345/coif). R.A.R. has received consulting fees from ITM Radiopharma, Regeneron, TerSera Therapeutics, Exelixis, Novartis, and Lantheus, serves on the speakers bureau for AstraZeneca, and is an unpaid Board of Directors member for the North American Neuroendocrine Tumor Society. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Comparison of (A,C) DFS and (B,D) OS before and after PSM between the LCNEC and SCLC groups. DFS, disease-free survival; LCNEC, large cell neuroendocrine carcinoma; OS, overall survival; PSM, propensity score matching; SCLC, small-cell lung cancer.
Figure 2
Figure 2
Comparison of DFS and OS between the LCNEC and SCLC groups according to TNM stage (A,B: stage I; C,D: stage II; E,F: stage III). DFS, disease-free survival; LCNEC, large cell neuroendocrine carcinoma; OS, overall survival; SCLC, small-cell lung cancer; TNM, tumor-node-metastasis.
Figure 3
Figure 3
Comparative analysis of DFS and OS between LCNEC and SCLC subtypes. (A,C) Comparison of DFS and (B,D) OS among the LCNEC and SCLC subtypes. (A) The DFS and (B) OS among the P-LCNEC and SCLC/LCNEC groups. The (C) DFS and (D) OS among the C-LCNEC and SCLC/non-LCNEC groups. C-LCNEC, combined large cell neuroendocrine carcinoma; DFS, disease-free survival; OS, overall survival; P-LCNEC, pure large cell neuroendocrine carcinoma; SCLC, small-cell lung cancer.
Figure 4
Figure 4
Kaplan-Meier survival curves of DFS and OS among patients with stage I LCNEC and SCLC treated with adjuvant chemotherapy and those not treated with adjuvant therapy (A: LCNEC; B: SCLC). DFS, disease-free survival; LCNEC, large cell neuroendocrine carcinoma; OS, overall survival; SCLC, small-cell lung cancer.
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