Advances in Systemic Therapy for Small Cell Lung Cancer

Small cell lung cancer (SCLC) represents approximately 15% of lung cancer cases and is strongly associated with tobacco use. Despite initial responsiveness to chemotherapy and radiotherapy, rapid recurrence and treatment resistance lead to poor long-term survival outcomes. This review outlines recent advancements in systemic therapy for SCLC, focusing on the evolving roles of personalized medicine and novel treatment strategies. Limited-stage SCLC (LS-SCLC) still relies on concurrent chemoradiotherapy, with recent and ongoing randomized trials evaluating the optimal dose and fractionation schedule. Technological refinements in radiation planning and delivery have reduced toxicity. Emerging evidence supports the addition of consolidation immunotherapy, specifically durvalumab, to improve progression-free survival. For extensive-stage SCLC (ES-SCLC), integrating immune checkpoint inhibitors like atezolizumab or durvalumab with chemotherapy has become the new standard, showing significant survival benefits. Personalized approaches leveraging molecular biomarkers such as Schlafen 11 (SLFN11) and delta-like ligand 3 (DLL3) offer promise for optimizing treatment responses. Emerging molecular subtypes based on transcription factor expression (e.g., ASCL1, NEUROD1) present opportunities for tailored therapies. Antibody-drug conjugates and novel targeted therapies, including PARP inhibitors, are under investigation to overcome resistance mechanisms. Smoking cessation and supportive care remain critical components of comprehensive management to enhance treatment efficacy and quality of life. Future research should focus on biomarker development, innovative therapies, and strategies for overcoming drug resistance to improve long-term outcomes. Ongoing clinical trials are essential for validating and integrating these strategies into clinical practice, ultimately aiming to transform SCLC treatment and improve patient survival.