Managing Patients With Oligometastatic Non-Small-Cell Lung Cancer

Abstract

Metastatic lung cancer has long been considered incurable, with the goal of treatment being palliation. However, a clinically meaningful number of these patients with limited metastases (approximately 25%) are living long term after definitive treatment to all sites of active disease. These patients with so-called oligometastatic disease likely represent a distinct clinical group who may possess a more indolent biology compared with their more widely metastatic counterparts. Hellman and Weichselbaum proposed the existence of the oligometastatic state, on the basis of the spectrum theory of cancer spread. The literature suggests that an oligometastatic state exists in patients with non-small-cell lung cancer (NSCLC). This observation in the setting of rapidly evolving systemic therapies, including immune checkpoint inhibitors and an increasing number of targeted therapies, represents a unique clinical opportunity. Metastasis-directed therapies to address sites of disease include surgery (metastasectomy) and/or radiation therapy. Available evidence suggests that treating patients with limited or oligometastases may improve outcomes in a meaningful way; however, the majority of the randomized data includes patients with intracranial metastatic disease, and there are limited robust, randomized data available in the setting of NSCLC with only extracranial sites of metastatic disease. Ongoing randomized trials, including NRG-LU002 and the UK Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases trial, are aimed at evaluating this question further. One of the current limitations of aggressive treatment of oligometastatic NSCLC is the inability to accurately identify these patients before therapy, yet molecular markers, including microRNA profiles, are being investigated as a promising way to identify these patients.