Optimize Local Therapy for Oligometastatic and Oligoprogressive Non–Small Cell Lung Cancer to Enhance Survival

Authors: Joe Y. Chang MD, PhD1 and Vivek Verma MD1
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  • 1 Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.

Metastatic non–small cell lung cancer (NSCLC) is highly heterogeneous, and there are patients with limited areas of metastases (oligometastases) or progression (oligoprogression) whose natural history and prognosis can be considerably more favorable. As a result, local therapy may offer these patients a chance at clinically meaningful disease control and/or cure. This review begins by describing the current status of the existing prospective data, including evidence of overall survival improvements from multiple randomized trials. Given the nascence of this realm, the review then examines ongoing controversies and unresolved issues regarding local therapy for oligometastatic and oligoprogression. First, the role of local therapy in the setting of targeted therapies and immunotherapy is discussed, because most published randomized trials of local therapy have been performed in the context of chemotherapy, which is no longer the standard of care for most patients with metastatic NSCLC. Refining patient selection for local therapy is then reviewed, including clinical factors (such as control of the primary and regional lymph node sites, the heterogeneous definitions of oligometastases/oligoprogression, and the underrepresentation of brain metastases in existing randomized data) and novel pathologic/molecular biomarkers. Next, because there also remains no consensus regarding the optimal modality of local therapy, the advantages and disadvantages of stereotactic radiotherapy, surgery, and other ablative techniques are discussed. Subsequently, methods to optimize radiotherapy are examined, including controversies regarding the optimal dose/fractionation and timing/sequencing scheme. A discussion regarding potentially extending the existing data to polymetastatic NSCLC follows. The review concludes with remarks regarding prudently designing randomized trials of local therapy going forward, including the benefits and drawbacks of specific endpoints meriting further testing in this unique population.

Submitted September 28, 2021; final revision received November 15, 2021; accepted for publication November 30, 2021.

Disclosures: The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Correspondence: Joe Y. Chang, MD, PhD, Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Email: jychang@mdanderson.org
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