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For stage I–III LCNEC, surgery is preferred, but high recurrence often makes surgery alone insufficient. Platinum-based adjuvant chemotherapy can improve survival, and for unresectable or metastatic disease chemotherapy is the first line, commonly cisplatin or carboplatin with etoposide or irinotecan. Response and survival remain limited, motivating investigation of immunotherapy, BiTEs, CAR-T cells, and oncolytic viruses. Overall 5-year survival is about 35.5% with 5-year recurrence-free survival of 27.4%. The review summarizes current literature on systemic treatment for LCNEC.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/clinical-practice-review-of-systemic-treatment-in-large-cell-neuroendocrine-carcinoma/355861/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/clinical-practice-review-of-systemic-treatment-in-large-cell-neuroendocrine-carcinoma/355861.png","ImageObject",300,407,{"name":92,"@type":93},"McGucket","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How is LCNEC of the lung treated when it is stage I–III?","Question",{"text":112,"@type":113},"Surgery is the preferred first-line treatment. Because recurrence rates are high, surgery alone is often not sufficient.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What chemotherapy regimens are commonly used for unresectable or metastatic LCNEC?",{"text":117,"@type":113},"Chemotherapy is generally the first line. It often combines either cisplatin or carboplatin with etoposide or irinotecan.",{"name":119,"@type":110,"acceptedAnswer":120},"Which emerging systemic therapies are discussed for LCNEC?",{"text":121,"@type":113},"The review discusses immunotherapy (not yet officially defined for LCNEC), bispecific T-cell engagers (BiTEs), and novel approaches including CAR-T cells and oncolytic viruses.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},355861,1790168183,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},1236954412713,"https://us-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Review Article  \nClinical practice review of systemic treatment in large cell neuroendocrine carcinoma  \nAmanda S. Cass1^, Isabella C. Luckage2, Albert G. Linden1, Robert A. Ramirez1^  \n1Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 2Vanderbilt University, Nashville, TN, USA  \nContributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final  \napproval of manuscript: All authors.  \nCorrespondence to: Amanda S. Cass, PharmD. Vanderbilt-Ingram Cancer Center, 2220 Pierce Ave Suite 1710, Nashville, TN 37232, USA.  \nEmail: [amanda.s.cass@vumc.org](amanda.s.cass@vumc.org).  \nAbstract: Large cell neuroendocrine carcinomas (LCNECs) of the lung make up only 3.1% of all primary lung cancers, making them highly uncommon when compared to other primary lung cancers. For patients with stage I, II, or III LCNEC of the lung, surgery is the preferred first-line treatment. However, due to high recurrence rates, surgery alone is often insufficient to fully treat patients’ disease. Adjuvant therapy utilizing platinum-based chemotherapy has been shown to improve survival in patients with LCNEC. For patients with unresectable or metastatic disease, chemotherapy is generally the first line of treatment, often a combination of either cisplatin or carboplatin with etoposide or irinotecan. However, the low response and survival rates leave room for advancement. There are several other treatments currently being investigated, which will be discussed in this review. Immunotherapy, which is often used to treat small-cell lung cancers, is yet to officially be defined as a treatment for LCNEC of the lung. Additionally, bispecific T-cell engagers (BiTEs) are also being explored in current trials as potential treatments and show promise as a potential treatment. Novel therapies such as chimeric antigen receptor T (CAR-T) cells and oncolytic viruses are being investigated. These studies are critical as patients with large cell neuroendocrine cancers tend to demonstrate poor 5-year survival rates at 35.5%, and even worse rates of 5-year recurrence-free survival at 27.4% . Given the aggressive nature and poor prognosis, further research into this disease is critical. We aim  \nto review and summarize the current literature on systemic treatment in LCNEC.  \nKeywords: Large cell neuroendocrine carcinoma (LCNEC); systemic treatment; neuroendocrine tumor  \nSubmitted Dec 05, 2025. Accepted for publication Apr 10, 2026. Published online May 26, 2026.  \ndoi: 10.21037/tlcr-2025-1-1394  \nView this article at: [https://dx.doi.org/10.21037/tlcr-2025-1-1394](https://dx.doi.org/10.21037/tlcr-2025-1-1394)  \nIntroduction  \nNeuroendocrine tumors (NETs) of the lung comprise a heterogeneous group of malignancies that arise from pulmonary neuroendocrine cells. These can be classified into four groups: typical carcinoid (TC), atypical carcinoid (AC), small-cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC). LCNEC of the lung  \nwas first described in 1991 as a pulmonary NET consisting of cells with large size, high mitotic rate, and with aneuroendocrine appearance both by light microscopy and either immunohistochemistry (IHC) or electron microscopy (EM) (1). The definition of LCNECs was further refined by the 2015 World Health Organization (WHO) Classification of Lung Tumors, and later by the 2021 classification (2,3) . According to the 2021 WHO criteria, lung neuroendocrine  \n^ ORCID: Amanda S Cass, 0000-0003-1761-4642; Robert A. Ramirez, 0000-0001-8762-5852.  \n© AME Publishing Company. Transl Lung Cancer Res 2026;15(5):147 | [https://dx.doi.org/10.21037/tlcr-2025-1-1394](https://dx.doi.org/10.21037/tlcr-2025-1-1394)  \nPage 2 of 9 Cass et al. Review of systemic treatment in LCNEC  \nTable 1 Key characteristics of 2021 WHO classifi","cbCaieseffhO9vHZ","https://ap.wps.com/l/cbCaieseffhO9vHZ","pdf",223961,"English","# Introduction\n## Classification and background of LCNEC\n# Systemic treatment overview\n## Surgery and recurrence risk\n## Platinum-based chemotherapy in different stages\n## Emerging therapies and clinical trials\n# Conclusion\n## Prognosis and need for further research","[{\"question\":\"How is LCNEC of the lung treated when it is stage I–III?\",\"answer\":\"Surgery is the preferred first-line treatment. Because recurrence rates are high, surgery alone is often not sufficient.\"},{\"question\":\"What chemotherapy regimens are commonly used for unresectable or metastatic LCNEC?\",\"answer\":\"Chemotherapy is generally the first line. It often combines either cisplatin or carboplatin with etoposide or irinotecan.\"},{\"question\":\"Which emerging systemic therapies are discussed for LCNEC?\",\"answer\":\"The review discusses immunotherapy (not yet officially defined for LCNEC), bispecific T-cell engagers (BiTEs), and novel approaches including CAR-T cells and oncolytic viruses.\"}]","Clinical practice review of systemic treatment in large cell neuroendocrine carcinoma | PDF",1790121362,23]