Surgery Remains Imperative in Biomarker-Driven NSCLC Era

David Mason, MD

Amid the ongoing explosion of immunotherapy and targeted agents in non—small cell lung cancer (NSCLC), surgery remains a key component of the armamentarium.

Surgery may be less of an option for patients with metastatic disease, but for those with NSCLC that is oligometastatic or who may benefit from a neoadjuvant or adjuvant systemic agent, removing tumors is now more essential than ever to the landscape, according to David Mason, MD.

“There are multiple areas where surgeons can be involved [that] we might not necessarily think of immediately,” Mason said. “[As with] the oligometastatic setting, patients in the induction setting may potentially have an added benefit to surgery, along with some of the other therapies that are [emerging]. Surgery for oligometastatic disease and surgery in the induction therapy setting are the 2 biggest areas I would focus on.”

OncLive^®: Please provide an overview of your discussion.

Can you expand on how the 2 have comingled and the impact on surgery?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Non—Small Cell Lung Cancer, Mason, chief of thoracic oncology and lung transplantation at Baylor University Medical Center, addressed the evolving role of surgery for patients with NSCLC.Mason: The main topics that I wanted to cover were how biomarkers have impacted the practice of surgery and where the 2 intersect, as well as where the future of surgical resection might be in light of what we are learning today regarding biomarkers. They have intermingled in several areas. One is to obtain tissue [from surgery] and put people on trials to generate more knowledge about the general genomics of lung cancer. Two, we are really looking at where biomarker therapies are intersecting with lung cancer. Those primarily are in the adjuvant setting, or treatment after lung cancer resection.

On the induction side of things, patients would get treatment prior to surgery based on the genetic evaluation of their tumors, and it would be directed therapy related to those biomarkers. [Patients may get treatment] in the adjuvant setting and in the induction setting prior to surgery.

Can you share insight on a scenario of neoadjuvant treatment?

There are settings that are more unusual, where a patient may have been treated for a more advanced cancer—potentially, a metastatic cancer—and have good response to treatment; their disease has stabilized; and, if they have a single residual focus of disease, surgical removal of that tumor might benefit them in the future. [At the meeting,] I gave a case presentation that really highlighted the metastatic setting. I had a patient who was relatively young, in her late 50s, who presented with a tumor that was metastatic to the brain. She was treated on a trial with a PD-L1 inhibitor that controlled her disease for 2 years. At the end of that therapy in that trial over the course of 2 years, she had a single residual area of tumor in her right lung and right upper lobe. The decision was to go ahead and take that out, given the fact that it might be her only site of disease. Her lung and surgical resection demonstrated no evidence of residual disease, and that patient is doing well right now.

What other types of patients with NSCLC would benefit from having surgical resection?

There is a setting of oligometastatic disease for biomarker-driven therapy, based on the findings that she had PD-L1 high expression and had PD-L1 treatment for 2 years on a trial, followed by surgical resection. That is a nice example of where those might intersect. It is an area we don’t know the answers to. Did surgery really benefit her? Are there other patients who might benefit? Is the treatment in that trial enough? Specifically, in the metastatic setting, these will be people who have oligometastatic disease or very few sites of metastatic foci, had a good response, and clearly respond to treatment. Obviously, nonresponders whose disease has progressed don’t seem likely to benefit from that. The patients who have very minimal disease—1 or 2 sites—might benefit. That is not a traditional approach for the use of surgery in cancer. Typically, we don’t operate in the metastatic setting, but that rarity might decrease over time.

Another area where there is value is in the adjuvant setting. That might be a larger subpopulation of patients, or patients receiving treatments in addition to surgery to try to improve long-term outcomes and diminish the likelihood of recurrence.

Following the progression of these therapeutic advancements, will surgery ever not be used for NSCLC?

There are some very interesting studies coming out now where induction has been used in other settings—not necessarily in the surgical setting but in the induction setting—showing very high efficacy for treatments of locally advanced tumors. This is particularly for stage III patients who are not getting surgery; in those patients, we’re learning that because of the effectiveness of those treatments, perhaps we could bring PD-L1 therapy to the surgical arena to further improve their outcomes. People have been talking about the future of oncology and the future of lung cancer without surgery. I don’t think that is ever going to happen. There is something about the biology of tumors where surgical removal will always be needed. It is something that provides job security to thoracic surgeons. In my lifetime, I don’t think that’s going to happen. Do I hope it happens for patients? I do. Do I think that’s likely to be the case? I don’t. Surgery will be an important mainstay of therapy when cure is entertained.