Small Cell Lung Cancer in the Era of Immunotherapy

Small cell lung cancer, accounting for approximately 14% of lung cancer cases, remains one of the most aggressive malignancies. Despite its lower incidence compared to non-small cell lung cancer, its early metastasis and rapid progression make small cell lung cancer a major public health concern due to poor survival outcomes. Five-year survival rates remain below 7% for extensive-stage disease, highlighting the urgent need for improved diagnostic and therapeutic strategies. Although epidemiologically small cell lung cancer is considered less hazardous than in previous decades, it continues to pose a substantial global public health burden. Changes in epidemiology include a narrowing of the historical male predominance, regional variations, and higher age-standardized incidence rates in Eastern Asia, Micronesia, Polynesia, Northern Europe, and North America. Although long-term survival remains limited, significant improvements with modern treatment options have been reported. Platinum-based chemotherapy combined with etoposide remains the first-line standard for both limited-stage and extensive-stage small cell lung cancer. Thoracic radiotherapy, prophylactic cranial irradiation to reduce the risk of brain metastases, and surgery for highly selected early-stage patients are among current treatment modalities, alongside second-line therapies such as topotecan. In parallel, novel therapeutic approaches primarily immunotherapies and patient-specific targeted therapies are showing substantial promise. The use of immune checkpoint inhibitors in combination with chemotherapy has been shown to improve survival in extensive-stage small cell lung cancer. Furthermore, integration of bispecific T-cell engagers targeting delta-like canonical Notch ligand 3, antibody-drug conjugates, poly-adenosine diphosphate ribose polymerase inhibitors, and epigenetic modulators with existing treatment strategies represents a promising direction for future therapy. Despite challenges including small trial sizes, resistance mechanisms, and treatment-related toxicity, these approaches may become more widely used in clinical practice. Overall, small cell lung cancer remains a serious clinical challenge that requires continued development of novel treatment strategies. These emerging approaches hold significant potential for providing more patient-specific therapeutic options. Ongoing and future clinical trials will be critical for establishing effective treatment algorithms and improving long-term outcomes in patients with this aggressive cancer. In this context, immunotherapy has emerged as a cornerstone of modern small cell lung cancer management, particularly in extensive-stage disease. Understanding the biological basis of immunotherapy responsiveness and resistance is therefore essential for optimizing current and future treatment strategies.