Surgery Stakes Claim in Lung Cancer Despite Evolution of Systemic Therapy

Surgical resection should be a standard of care for patients with stage I to IIIA lung cancer, according to Benjamin E. Lee, MD, who recommended probing for subclinical stage III disease with endobronchial ultrasound guided biopsy or mediastinoscopy to determine whether surgery should be performed prior to or after systemic therapy.

“For patients with known stage IIIA disease, I do believe in systemic therapy prior to surgery,” said Lee. “So, I will readily get a medical oncologist involved, unless for some reason the patient has a demand or preference that they don’t want chemotherapy.”

In an interview with OncLive®, Lee, chief of Thoracic Surgery and an assistant professor of Clinical Cardiothoracic Surgery in the Department of Cardiothoracic Surgery at NewYork-Presbyterian/Queens, discussed current considerations for surgical resection in early-stage lung cancer and potential palliative benefits in the metastatic setting.

OncLive®: How collaborative is the working relationship between pathologists, radiation oncologists, medical oncologists, and surgeons in the treatment of patients with lung cancer?

Lee: Ideally, it would be a very collaborative one. It really varies from practice setting to practice setting. I currently practice in somewhat of an academic environment. There are [National Comprehensive Cancer Network] guidelines on how to treat [patients with] lung cancer, and a lot of it is stage specific, but it involves more than just 1 person, especially when you get into the middle and upper stages of disease. A single doctor is not going to go at the treatment of lung cancer alone.

From that perspective, we have our colleagues that we work with, whether it be in medical oncology, radiation oncology, pathology, and whatnot. Recently, I spoke with a pathologist regarding specific testing. [The care of patients with lung cancer] involves reaching out to people, but you have to be available to let people reach out to you as well. There’s always an open level of communication between providers. In this day and age, it really is important that there is a team aspect when you are trying to treat lung cancer.

How common are referrals to surgery because of incidental findings on imaging?

As a surgeon, we predominantly will see patients with early-stage disease. Frequently, we will be referred patients without a diagnosis of lung cancer, and instead just have a suspicion of lung cancer, either based on a screening CT scan or an incidental finding in a workup another problem. A patient [may have] an X-ray or a CT scan preoperatively, and they just happen to pick [a lesion up]. We frequently even see patients that are having cardiac CT scans to look at calcifications of their heart, and they just happen to pick up a nodule in the lung. A lot of the patients with stage I disease that we see [are referred to us because of] incidental findings, or [findings from] screening scans for those that are at risk. Our role will then be to make a decision regarding the likelihood of [that lesion] being cancer, and what the potential treatment options are going to be, whether biopsy, surgery, or things like that.

What factors are you using to determine if a patient can undergo surgery, and which type?

If you have a patient without a diagnosis, and they just have a solitary lung nodule, the discussion, a lot of times, will revolve around whether or not to do a biopsy of that nodule, first and foremost, versus simply removing the nodule. A lot of things do go into that consideration, such as the patient themselves and their risk factors. [Additionally,] are they a smoker, and how old are they? Those become important details. Change over time [also has to be taken into consideration]. Is this a patient who had multiple CT scans that you can document growth over time, or change in density of the lesion over time?

When it comes to procedures, location of the lesion also becomes important. Some nodules are very deep seated within the lung, and some are very peripheral. When we talk about doing a needle biopsy, the conversation always brings up part of the risks of needle biopsies and the negative diagnostic rate of a needle biopsy, given the smaller amount of tissue that’s obtained. Somewhere between 10% and 15% of those biopsies may not be diagnostic.

We also talk about that with surgical procedures. If a nodule is in a particular location that may be amenable to an initial diagnostic wedge resection, that doesn’t involve removal of a lot of the normal lung tissue, where we can get an initial frozen section and get an intraoperative diagnosis before doing a more anatomic or planned resection.

Our standard operation for patients with lung cancer––this being a pretty big generalization––is a lobectomy where the lobe of the lung that has the lung cancer is removed. However, more and more, we have a lot of other circumstances that may demand a lesser operation, which we call a sublobar resection and would be a wedge resection or a segmental resection, especially in patients with diminished pulmonary function status, or very small tumors that are less aggressive [and are] part solid in their appearance. A lot of factors, both imaging and patient wise, [help us decide] what type of operation a patient may or may not need.

Should radiation be reserved for patients who are not eligible for surgery?

One of the discussions that always goes on when we’re talking about someone with a known diagnosed lung cancer is going to be treatment options that are both surgical and non-surgical. Some patients who come to see us may already have a known diagnosis; they already underwent a biopsy. It is important that patients know that they have options. Generally speaking, radiation or non-surgical treatment for early-stage lung cancer is very effective, and it’s most effective when the tumors are smaller.

However, it is also a treatment that isn’t without side effects, and it also isn’t without failure. We do talk about the fact that, generally speaking, surgery is preferred to radiation as the long-term results have been shown to be better.

Radiation is generally a modality that’s reserved for patients who either can’t have lung surgery, because their pulmonary status is too poor, or their cardiac status is too poor, or they just don’t want to have surgery. Therefore, it ends up being more of a second option—but it’s not a terrible option. It actually has very good long-term results. It’s just when compared with a defined surgical resection, most of the studies that have been done do not show clinical equipoise, and surgery does [lead to] better long-term results.

What are your thoughts on the evolution of immunotherapy in the early-stage setting?

The role of PD-1/PD-L1 therapy is being investigated by a number of different sites and centers, and how that can be used in the neoadjuvant setting and adjuvant setting. That’s going to be interesting, because the ADAURA study targeted EGFR mutations, but that’s not the majority of lung cancer. That is actually a minority of patients with lung cancer. Those kind of data will be coming out at some point and will be very interesting.

Should patients with early-stage disease be referred to surgeons before medical oncologists?

It varies [depending on] how people practice. I would like to think that the way I practice is close to the standard of care. I would say that the traditional [approach is] that stage I and II lung cancers are operated on when possible, with the caveat that if I suspect someone has stage II lung cancer, I would push to invasively biopsy the mediastinum to really make sure that they don’t have stage III disease by endobronchial ultrasound guided biopsy or mediastinoscopy. A small percentage of those patients do have subclinical disease and truly do have stage III disease. For patients with known stage IIIA disease, I do believe in systemic therapy prior to surgery. Therefore, I will readily get a medical oncologist involved, unless for some reason the patient has a demand or preference that they don’t want chemotherapy. Every now and then, we run into those circumstances, but most of time, most patients are pretty reasonable. We try to provide an explanation of the research behind the use of induction therapies in stage IIIA disease.

Patients with higher stages, such as IIIB and above, generally speaking, are not ones that we generally would offer surgical therapies to, and would push them more towards non-surgical treatment, with combined chemoradiation, for example. In this day and age, a lot of new things are coming out, especially with targeted treatments. That also adds a couple of new wrinkles, especially in patients that do have actionable mutations.

How have the ADAURA data affected treatment approaches in the adjuvant setting?

Osimertinib [Tagrisso] is approved [as an adjuvant therapy for patients with EGFR mutations]. ADAURA is one study that was published and presented, but the data are remarkably good. I don’t personally prescribe osimertinib, but I have had a conversation with multiple oncologists who do feel very excited about the data, and they’re the folks that have been prescribing these EGFR-targeted drugs for years now. Oncologists probably have had some level of yearning or excitement to use these drugs in the adjuvant setting, but just never had the data to support their use. Therefore, a trial like ADAURA gives them that option.

One of the issues that I have with the study, which is not so cut and dry, is that a portion of the patients had chemotherapy and osimertinib, and a portion of the patients didn’t. It also leaves open the question of: What is the role of radiation therapy in these patients? It’s a good first study that probably needs additional follow-up studies that are more defined that also might help validate the data as well. However, the study was well run, and the data do show a very significant improvement in patients with EGFR mutations. That likely does correlate to some of the data that follows patients with metastatic disease that have been receiving the same drugs.

What would you like to emphasize about the way lung cancer treatment is evolving?

For the longest period of time, all we really had was platinum-based doublet chemotherapy. We’ve always had some kind of radiation therapy, and we’ve always had some kind of surgery, whether it be very invasive, open surgery, or more minimally invasive surgery nowadays. But that’s it. That has kind of been the lung cancer story for 3 decades, but really in the last 10 to 15 years or so, we’re seeing so much more research going on. There are a lot of new exciting treatments that are showing a lot of therapeutic benefit. We’re finally going to start having an impact on lung cancer survival. For the longest time, lung cancer survival has always just been dismal. There’s a lot of hope with these new therapies, especially as we get more data and more studies done, not only in patients with stage IV disease, but with stage III, II and even late stage I disease.