Update 2026: Management of Small Cell Lung Cancer.

Abstract

Small cell lung cancer (SCLC) remains a biologically aggressive neuroendocrine carcinoma characterized by early metastatic spread, frequent relapse, and poor long-term survival. After several decades of limited progress, recent therapeutic advances have begun to reshape management across disease stages. In limited-stage SCLC, concurrent platinum-etoposide chemoradiotherapy remains the backbone of curative-intent treatment, while consolidation durvalumab after chemoradiotherapy has established a new standard for patients without disease progression. In extensive-stage SCLC, platinum-etoposide plus a PD-L1 inhibitor remains the preferred first-line approach. For selected patients, maintenance lurbinectedin plus atezolizumab and second-line tarlatamab have expanded treatment options beyond conventional cytotoxic chemotherapy. Intracranial management is also evolving, with greater emphasis on baseline brain magnetic resonance imaging, longitudinal surveillance, selective use of prophylactic cranial irradiation, stereotactic radiosurgery in appropriate patients, and neuroprotective strategies during whole-brain radiotherapy. Biologically, SCLC is increasingly recognized as a heterogeneous disease. Transcriptional subtypes, DLL3, B7-H3, SEZ6, SLFN11, and circulating tumor DNA are informing clinical trial design and may help refine future treatment selection. This review provides a clinically oriented overview of current standards and emerging therapeutic strategies in SCLC, with attention to evidence quality, toxicity, sequencing, and clinical applicability. It also discusses key unresolved questions that must be addressed before biomarker-directed and subtype-informed treatment can be integrated into routine practice.