Limited-Stage Small-Cell Lung Cancer: Current Progress and the Next Frontier

Limited-stage (LS) small-cell lung cancer (SCLC) is defined as disease confined to a tolerable radiation portal without extrathoracic metastases. Despite clinical research over two decades, the prognosis of LS-SCLC patients remains poor. The current standard of care for LS-SCLC patients is concurrent platinum-based chemotherapy with thoracic radiotherapy (RT). Widespread heterogeneity on the optimal radiation dose and fractionation regimen among physicians highlights the logistical challenges of administering BID regimens. Prophylactic cranial irradiation (PCI) is recommended to patients following a good initial response to chemoradiation due to improved overall survival from historical trials and the propensity for LS-SCLC to recur with brain metastases. However, PCI utilization is being debated due to the greater availability of magnetic resonance imaging (MRI) and data in extensive-stage SCLC regarding close MRI surveillance in lieu of PCI while spurring novel RT techniques, such as hippocampal-avoidance PCI. Additionally, novel treatment combinations incorporating targeted small molecule therapies and immunotherapies with or following radiation for LS-SCLC have seen recent interest and some concepts are being investigated in clinical trials. Here, we review the landscape of progress, limitations, and challenges for LS-SCLC including current standard of care, novel radiation techniques, and the integration of novel therapeutic strategies for LS-SCLC.