Small cell lung cancer: a therapeutic update in the era of immunotherapy and beyond—a narrative review

BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with frequent relapse and poor long-term survival. We review current and emerging therapeutic strategies across disease stages, emphasizing multimodal treatment and novel systemic agents. METHODS: We performed a narrative review based on a comprehensive literature search in PubMed, Embase and the Cochrane Library for studies published up to 1 April 2025, with late-breaking abstracts considered through July 2025. Medical Subject Headings (MeSH) and free-text terms related to small cell lung cancer, chemotherapy, immunotherapy, radiotherapy, surgery and emerging agents were combined with Boolean operators. No language restrictions were applied. KEY CONTENT AND FINDINGS: For limited-stage disease, concurrent platinum-etoposide chemoradiotherapy remains the backbone, and durvalumab consolidation after definitive chemoradiotherapy has become a new standard based on the ADRIATIC trial. For extensive-stage disease, first-line chemoimmunotherapy with atezolizumab or durvalumab combined with platinum-etoposide is the current standard of care, and emerging data support selected maintenance strategies. In relapsed disease, outcomes remain poor, but lurbinectedin, DLL3-directed bispecific T-cell engagers such as tarlatamab, and antibody-drug conjugates targeting B7-H3 or TROP-2 show early activity. Transcriptional plasticity and intratumor heterogeneity are increasingly recognized as key drivers of treatment resistance. CONCLUSIONS: While immunotherapy has improved outcomes, most patients ultimately relapse. Integrating molecular subtyping, optimizing multimodality care, and accelerating clinical trial enrollment are key to further progress in SCLC.