expert roundtables

Oligometastatic Non–Small Cell Lung Cancer: Definitions and Treatment Principles

by Roy S. Herbst, MD, PhD; Bruce E. Johnson, MD; and Gregory J. Riely, MD, PhD

Overview

There is growing interest in the treatment of oligometastatic non–small cell lung cancer (NSCLC), where local therapy (eg, surgery, radiotherapy) is applied to locally confined disease and systemic therapy is applied to distant metastatic disease. Still, issues of case definition persist, and practitioners are cautious about seemingly oligometastatic presentations that are actually heralding events of widespread metastasis.

Q:

How is oligometastatic NSCLC  best defined, and what are some reasonable treatment approaches for differing oligometastatic presentations?

Gregory J. Riely, MD, PhD

Vice Chair, Clinical Research
Department of Medicine
Memorial Sloan Kettering Cancer Center
New York, NY

“For treatment of oligometastatic disease, the traditional treatment approach has been the same as with other types of metastatic disease; however, 2 recent developments are changing that.” 

Gregory J. Riely, MD, PhD

Although the notion of oligometastatic disease  has been around for a long time, beginning with early descriptions by Ralph R. Weichselbaum, MD, unfortunately, there is still no real consensus on its definition today. In clinical trials, definitions have ranged from as few as 3 metastases to as many as 10; and some definitions are based on the number of organs involved rather than the number of metastases (eg, you could have 3 spots in the lung that might be counted as a single area). A slightly different concept, that of oligoprogressive disease, refers to the development of a single site of disease that becomes resistant to targeted therapy or immunotherapy while other sites remain controlled. For patients with oligoprogressive disease, I definitely explore the use of local therapies for that single site of progression.

For treatment of oligometastatic disease, the traditional treatment approach has been the same as with other types of metastatic disease; however, 2 recent developments are changing that. The first is our improved ability to treat individual sites of disease with more advanced radiation therapy technology. The second is our improved ability to control systemic disease. There are numerous interesting investigational approaches for oligometastatic disease, and there are reports of effective treatment approaches for oligometastasis, often combining effective systemic therapies with focused radiation therapy. When I see a patient with oligometastatic disease today, I largely treat them with systemic therapy alone; except, perhaps, if they have brain metastases. For these patients, I may treat the brain metastases with radiation therapy and then begin systemic therapy. 

However, it should be stressed that, before we start considering such approaches, whether up front or in the oligoprogressive setting, we need a thorough staging evaluation. Going forward, in conducting clinical trials, there needs to be a consensus on the definition of oligometastatic and on the best primary outcome to assess in clinical trials. Most of us agree that improving overall survival remains the critical objective of treatment. 

Roy S. Herbst, MD, PhD

Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology
Chief of Medical Oncology
Director, Thoracic Oncology Research Program
Associate Director for Translational Research
Yale Cancer Center
Yale School of Medicine
Smilow Cancer Hospital
New Haven, CT

I tend to favor the approach of treating systemically first, realizing that, in metastatic disease, there are usually—although not always—multiple sites of involvement. Then, if there is a certain area that is not responding, you still have that option to use radiation therapy or surgery to remove the metastasis.” 

Roy S. Herbst, MD, PhD

Oligometastatic disease is definitely a challenge. I agree with Dr Riely in that, although some patients with stage IV NSCLC may have a metastasis in only a single site (eg, the brain, the adrenal gland), other metastases may already be present at that point. Systemic therapy with chemotherapy, targeted therapy, or immunotherapy would oftentimes be an appropriate starting point in that situation. If a patient has already been in consultation for surgery, there might be an inclination to perform an aggressive resection right away. I tend to favor the approach of treating systemically first, realizing that, in metastatic disease, there are usually—although not always—multiple sites of involvement. Then, if there is a certain area that is not responding, you still have that option to use radiation therapy or surgery to remove the metastasis. We have done this on a number of occasions with adrenal metastases and with small brain metastases, where the tumor continues to grow after immunotherapy.

You want the patient to be as disease free as possible, but when you realize that you are dealing with a systemic problem, and the patient is asymptomatic, you might not be as eager to recommend an invasive local approach. You really want to have certainty that the patient is truly oligometastatic and that you are not missing other sites of metastasis. You want to avoid the scenario where a radical surgery or risky brain procedure is performed, only to be followed very soon thereafter by widespread metastatic disease.

Bruce E. Johnson, MD

Institute Physician
Dana-Farber Cancer Institute
Professor of Medicine
Harvard Medical School
Boston, MA

“It remains to be determined definitively whether LCT with radiation therapy or surgery improves outcomes in patients with oligometastatic NSCLC, but data thus far suggest that LCT improves not only progression-free survival but also overall survival.” 

Bruce E. Johnson, MD

Those of us who have treated patients with lung cancer for quite a while have seen patients who have either a single lesion or up to 3 metastatic lesions, and the question of whether they would be helped by localized radiation or surgery resection arises. It remains to be determined definitively whether local consolidative therapy (LCT) with radiation therapy or surgery improves outcomes in patients with oligometastatic NSCLC (NCT02170181), but data reported by Gomez et al suggest that LCT improves not only progression-free survival but also overall survival.

Oligometastatic disease is definitely one of the things that I think about, for instance, when I see someone with a single dominant residual mass with other complete responses. Consider a patient who, at initial presentation, is found to have EGFR-mutated NSCLC and is treated with a tyrosine kinase inhibitor. Then, approximately 1 year later, it recurs locally in a single hilar lymph node; no other sites are identified on positron emission tomography/computed tomography at the time of recurrence. In that scenario, it is worth consulting radiation oncology to see if that lymph node can be easily irradiated. Although we do not have a clinical trial open at this time, I will think about using radiation or even exploring the possibility of surgical resection of the local area in that situation. There can be synchronous and metachronous manifestations of oligometastatic NSCLC. The scenario just described would be considered metachronous. In a synchronous presentation, the patient may have 2 sites at the same time (eg, a primary tumor in the left lung, no nodal involvement, and a contralateral lesion in the area of the clavicle and first rib). The question then becomes: Do you treat both synchronous oligometastases locally?

References

Ashworth A, Rodrigues G, Boldt G, Palma D. Is there an oligometastatic state in non-small cell lung cancer? A systematic review of the literature. Lung Cancer. 2013;82(2):197-203.

ClinicalTrials.gov. Clinical registry for oligometastatic disease, consolidation therapy, debulking prior to chemotherapy, or re-irradiation. Accessed May 10, 2020. https://clinicaltrials.gov/ct2/show/NCT02170181

Giraud N, Abdiche S, Trouette R. Stereotactic radiotherapy in targeted therapy treated oligo-metastatic oncogene-addicted (non-small-cell) lung cancer. Cancer Radiother. 2019;23(4):346-354.

Gomez DR, Tang C, Zhang J, et al. Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study. J Clin Oncol. 2019;37(18):1558-1565.

Ning MS, Gomez DR, Heymach JV, Swisher SG. Stereotactic ablative body radiation for oligometastatic and oligoprogressive disease. Transl Lung Cancer Res. 2019;8(1):97-106.

Schroeder SR, Leenders M, Iyengar P, de Ruysscher D. Changing equipoise in the landscape of radiation for oligometastatic lung cancer. Transl Lung Cancer Res. 2019;8(suppl 2):S184-S191.

Torok JA, Gu L, Tandberg DJ, et al. Patterns of distant metastases after surgical management of non-small-cell lung cancer. Clin Lung Cancer. 2017;18(1):e57-e70.

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