Local consolidative therapy for oligometastatic patients with stage IV non-small cell lung cancer may improve survival, but unanswered questions remain

Oligometastatic disease refers to a limited number of metastatic sites that are either “synchronous” when presenting at the time of initial diagnosis or “metachronous” when arising following therapy of the primary tumor. It is hypothesized that the biology of oligometastatic tumors may be different than that of tumors with more widespread metastases (1-3). As such, treatment of oligometastatic sites with local consolidative therapy (LCT) is a topic of interest, and has been increasingly offered in clinical practice. While there is no single definition of this state, it is commonly defined as up to 3–5 sites of metastases (excluding the primary lesion) following induction systemic therapy (1-6). In patients receiving chemotherapy for non-small cell lung cancer (NSCLC), it has been observed that the most common sites of progression are within the original disease sites (1-3,6). Patients with oligometastatic disease remaining after induction systemic therapy are believed to harbor treatment resistant clones in these sites which may not be effectively managed with subsequent systemic agents (7). In these cases, there is a widow of opportunity to eradicate radiographically visible disease sites with LCT and delay further progressive disease, and perhaps even help patients live longer (1,8,9). Initially, highly select patients with limited metastases were treated off trial with LCT to all visible disease sites, including to the primary tumor (10). Later, retrospective observational studies and single arm prospective trials suggested a potential survival benefit with this approach (11-14). In a meta-analysis of 757 NSCLC patients with or without prior chemotherapy, and having 1-5 sites of metastases, the delivery of LCT to all visible disease sites (62% surgery and 38% radiation) was associated with a 5-year overall survival (OS) rate of 29.4% (15). When considering the historical 5-year OS rate of 2% in stage IV NSCLC patients, this approach received widespread attention (16). However, this meta-analysis was subject to selection bias as it did not include randomized prospective data. Additionally, the historical rates included patients with any number of metastatic sites, and as such the patients treated with LCT for oligometastatic disease may have simply done better because their disease burden was lower. Subsequently, randomized clinical trials were initiated to more rigorously evaluate the role of LCT vs. standard systemic therapy/observation in patients with oligometastatic disease following induction chemotherapy (4-6).