Changing equipoise in the landscape of radiation for oligometastatic lung cancer

There is growing interest in exploring use of local therapies in the management of oligometastatic non-small cell lung cancer (NSCLC) to provide durable local and distant disease control. Prospective phase II studies have incorporated local therapy (predominantly stereotactic ablative radiotherapy or SABR) to both primary and metastatic sites. For patients who received these treatments, median progression-free survival (PFS) and overall survival (OS) exceeded that of historical controls treated with systemic therapy alone (9.7-23.5 and 13.5-41.2 months, respectively). Additionally, three trials randomized oligometastatic NSCLC patients to standard of care systemic therapy regimens vs. local consolidative therapy (LCT) plus standard of care systemic therapy (or observation) and all demonstrated a significant improvement in PFS, with two showing OS benefits to date. Notably, a majority of these trials selected patients with at least stable disease after completion of systemic therapy for local therapy and defined the oligometastatic state as one with no more than five metastatic sites spread across three organs. For patients with oligometastatic NSCLC, there are many important factors that should drive use and timing of local therapy, including metastatic presentation sequence (synchronous vs. metachronous), extent of disease (number and distribution of sites), and quality of life goals. The referenced clinical trials accrued patients prior to the approval of immunotherapy for metastatic NSCLC, so the benefits of any local therapy in this setting remain uncertain. To ultimately clarify the role of local therapy in oligometastatic NSCLC in the era of improving systemic therapy efficacy (i.e., immunotherapy and targeted therapy combinations with cytotoxics), we recommend enrollment in in phase III studies with OS endpoints (i.e., NRG LU 002 and SARON) whenever possible. These and other important issues associated with local therapy for oligometastatic NSCLC are reviewed in this paper.