Radiation for Oligometastatic Lung Cancer in the Era of Immunotherapy: What Do We (Need to) Know?

SIMPLE SUMMARY: The historical standard treatment of metastatic non-small cell lung cancer (NSCLC) consisted of palliative chemotherapy, with limited influence on survival. With the introduction of immuno- and targeted therapy, the prognosis improved largely. A subset of NSCLC patients with limited metastatic disease, called oligometastatic, might obtain long-term survival by adding a local ablative treatment on all visible disease sites, in addition to the standard systemic treatment. The evidence for this combined treatment is still scarce and comes mainly from the pre-immunotherapy era. As radiotherapy might stimulate the immune system making immunotherapy more efficient, here we review the evidence before and in the era of immunotherapy, and discuss the challenges and prospects of the combined treatment. ABSTRACT: Oligometastatic cancer is recognized as a separate entity within the spectrum of metastatic disease. It was suggested that patients with oligometastatic disease can obtain long-term survival by giving local ablative therapy (LAT) to all visible disease locations. However, the true extent from which metastatic cancer should be called “oligometastatic” is unknown, although a consensus definition for oligometastatic disease is proposed by research organizations, such as the EORTC (maximum of five metastases in three organs). Different states of the oligometastatic disease are defined, such as synchronous vs. metachronous, oligopersistent vs. oligoprogressive disease. All clinical trials including patients with non-small cell lung cancer (NSCLC) are small and most are not randomized. Two small randomized phase II trials on synchronous disease showed an improvement in progression free survival, with the addition of LAT, and one also demonstrated an overall survival benefit. Immune checkpoint inhibitors (ICI) were not part of the treatment in these trials, while ICI significantly improved long-term outcomes of patients with metastatic NSCLC. Radiotherapy might improve the prognosis of patients treated with ICI because of its immunostimulatory effects and the possibility to eradicate metastatic deposits. Here, we summarize the data for adding ablative radiotherapy to the treatment of oligometastatic NSCLC, especially in the ICI era, and discuss the challenges of combined treatment.