Pulmonary Large-Cell Neuroendocrine Carcinoma: Molecular Heterogeneity, Current Treatment and the Emerging Precision-Oncology Paradigm
5 affiliations
- 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Gangshan Hospital, Kaohsiung Medical University, Kaohsiung 820011, Taiwan
- 3Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 80708, Taiwan
- 4Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- 5School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Abstract
Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive malignancy with substantial biological heterogeneity. Genomic studies identify SCLC-like and NSCLC-like spectra, but genomic categories overlap incompletely with transcriptional states. Morphology remains essential: neither neuroendocrine marker positivity nor RB1 status alone distinguishes LCNEC from small-cell lung cancer (SCLC). This narrative review integrates diagnostic limitations, stage-based management, and the clinical implications of profiling. Surgery with systematic nodal assessment is central for resectable disease; postoperative platinum chemotherapy has greater support than perioperative immunotherapy. In advanced disease, platinum-etoposide is a commonly used reference regimen. Retrospective associations involving platinum-gemcitabine or platinum-taxanes in RB1-wild-type tumors remain hypothesis-generating and should not be extended to pemetrexed. LANCE, a durvalumab phase II trial, and preliminary NEJ044 findings provide prospective chemo-immunotherapy observations, although randomized LCNEC-specific evidence remains absent. No standard second-line regimen is established. Rare actionable drivers may support matched treatment, whereas DLL3-directed approaches and FGL1/SPINK1-associated strategies require clinical validation. We propose an evidence-qualified framework separating stage-based care, individualized molecular considerations, and clinical-trial strategies.
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BibTeX
@article{lee2026pulmonary,
title = {{Pulmonary Large-Cell Neuroendocrine Carcinoma: Molecular Heterogeneity, Current Treatment and the Emerging Precision-Oncology Paradigm}},
author = {Tai-Huang Lee and Juei-Yang Ma and Huei-Yang Hung and Chia-Yu Kuo and Chin-Ling Chen and Pei-Chi Tsai and Cheng-Hao Chuang and Chih-Jen Yang},
journal = {Cancers},
year = {2026},
month = nov,
doi = {10.3390/cancers18213585},
url = {https://www.mdpi.com/2072-6694/18/21/3585},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pulmonary Large-Cell Neuroendocrine Carcinoma: Molecular Heterogeneity, Current Treatment and the Emerging Precision-Oncology Paradigm
AU - Tai-Huang Lee
AU - Juei-Yang Ma
AU - Huei-Yang Hung
AU - Chia-Yu Kuo
AU - Chin-Ling Chen
AU - Pei-Chi Tsai
AU - Cheng-Hao Chuang
AU - Chih-Jen Yang
PY - 2026
DA - 2026/11/07
JO - Cancers
DO - 10.3390/cancers18213585
UR - https://www.mdpi.com/2072-6694/18/21/3585
AB - Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive malignancy with substantial biological heterogeneity. Genomic studies identify SCLC-like and NSCLC-like spectra, but genomic categories overlap incompletely with transcriptional states. Morphology remains essential: neither neuroendocrine marker positivity nor RB1 status alone distinguishes LCNEC from small-cell lung cancer (SCLC). This narrative review integrates diagnostic limitations, stage-based management, and the clinical implications of profiling. Surgery with systematic nodal assessment is central for resectable disease; postoperative platinum chemotherapy has greater support than perioperative immunotherapy. In advanced disease, platinum-etoposide is a commonly used reference regimen. Retrospective associations involving platinum-gemcitabine or platinum-taxanes in RB1-wild-type tumors remain hypothesis-generating and should not be extended to pemetrexed. LANCE, a durvalumab phase II trial, and preliminary NEJ044 findings provide prospective chemo-immunotherapy observations, although randomized LCNEC-specific evidence remains absent. No standard second-line regimen is established. Rare actionable drivers may support matched treatment, whereas DLL3-directed approaches and FGL1/SPINK1-associated strategies require clinical validation. We propose an evidence-qualified framework separating stage-based care, individualized molecular considerations, and clinical-trial strategies.
SN - 2072-6694
ER -