Surgical Planning in Early-Stage NSCLC Grows More Complex in the Biomarker Era

Surgical decision-making in early-stage non–small cell lung cancer (NSCLC) is becoming increasingly complex as biomarker-directed therapy moves into earlier lines of care. What was once a relatively streamlined process centered on staging and operative fitness now requires surgeons to incorporate molecular data, coordinate additional testing, and navigate longer timelines before intervention. These shifts are not only changing how surgeons plan resections but also how they collaborate across specialties to determine the optimal treatment sequence, according to Jessica Donington, MD, MSCR.

“For the past 20 years, medical oncologists have tackled biomarkers and biomarker-directed therapy. It is exciting that [targeted therapy has] made it to the surgical space, but that does complicate what we do. There is no doubt about it. My patient evaluation used to be entirely about staging and physiologic evaluation. [I would ask] what surgery they need and whether they were strong enough for it. Now, I’ve added this whole additional [element to] the workup, [so I can consider] what their tumor tells me,” Donington said in an interview with OncLive®.

In the interview, Donington, a professor of surgery and chief of the Section of Thoracic Surgery at UChicago Medicine in Illinois, discussed some of the logistical challenges that accompany the integration of biomarker testing into early-stage workflows and how it has redefined the role of multidisciplinary care in guiding patients from diagnosis to treatment.

OncLive: From a surgical perspective, how has the emergence of biomarker-directed therapy affected surgical planning within early-stage NSCLC?

Donington: Having to get biomarker testing [changes] what we do. The frustration for surgeons [is that] it adds a bit more delay [to the process] than we are used to. We’re used to being able to move very quickly, but now not only do more of our patients require an invasive biopsy, but also the testing [that is required] after that. In the surgical world, all the biopsies are going to be small––they’re all needle biopsies––and there’s always a push and pull between making the most of the tissue, which is probably going to be next-generation sequencing [NGS]. NGS tends to take a bit longer as opposed to point of care testing, which saves time but requires more tissue. Every surgeon is now in the middle of that argument with their pathologist and their institutions.

When a patient presents with suspected lung cancer, what other specialists are involved to help with the diagnosis and treatment planning?

For patients who have early to locally advanced lung cancer, the team providing care has gotten a bit bigger. With the introduction of navigational bronchoscopy and the refinement of endobronchial ultrasound [EBUS], the interventional pulmonologists have a bigger role than they ever had before. We still use interventional radiology in many of our tumor boards, but they may be getting slightly less [involved] because EBUS plus navigational bronchoscopy should provide a one stop shop for patients to get diagnosed and staged, and receive adequate biomarker testing prior to treatment. With respect to biomarker testing, [which now includes PD-L1, EGFR, and ALK], the pathologist is front and center in the treatment decision. The molecular pathologist is part of the [decision-making team] more than ever before.

Within your institution, what are some of the strategies that you and your colleagues use to ensure patients are being processed with expediency?

I am fortunate that I work in a large academic institution, and we ensure that a team is always available for anyone who has clinic on campus. If a surgeon is in clinic, there should be a medical oncologist, interventional pulmonologist, and a radiation oncology in clinic as well. Although we don’t all share the same space, we know who is on our team and our patients [benefit from] an open-door policy to see any one of those doctors on any given day. That has made a huge difference in getting people through the system.

That way, the patients don’t have to wait a week or two for a multidisciplinary clinic to find out whether they’ll need induction therapy and resection or chemoradiation and some type of immunotherapy. I do find that a little more challenging when I’m at my smaller outreach clinics, but we’ve tried to set that network up each day, and everyone has been supportive of making that happen.

Is there a notable example you can share illustrating the benefits of such an approach?

We had a patient who was screened who I saw at one of our smaller outreach clinics, not at the university campus. She showed up from her primary care doctor, and we were her first [touchpoint]. She said she was told she had a nodule. She had more than a nodule, and that was one of those days when I had to go down and negotiate with a busy medical oncologist to see her and get her started [on her treatment journey]. I had to get on the phone and talk to my pulmonologist [because I felt] she needed to be seen immediately. We had to perform some of the labs and anesthesia work in my clinic, but within 3 weeks we had her seen by everyone. We had her biopsied, and we had her molecular analysis, and suddenly we were ready to start treatment.

She just completed everything, including her surgery. She got induction chemoimmunotherapy, and she ended up having a pathologic complete response [pCR], but it’s a long road. You have to get them set for that and try to get as many of those things to happen in the beginning as possible. I also tell my patients who look like they have stage II or III disease that it’s going to take probably a month to have a plan. You have to set that expectation [with them] that you’re not going to start treatment at the end of the week. There are too many things that have to happen. You also want to warn them that their surgery is going to be 3 to 4 months from [the time they’re being seen]. We also try hard to keep having touch points during their induction therapy, so they don’t forget about us. But, if they’re starting to struggle, [it’s always good to have] another set of eyes to say whether something has to change or [suggest] a different plan.

How do you try to ease patient anxiety during that waiting period?

I explain what all the steps are, and I write it all down. [I tell them], ‘you’re going to need a biopsy and it’s going to have to get mutational testing. We’re going to [attend a] tumor board, and then we’re going to see [how everyone feels we should proceed], and this is what you and I can do in the meantime.’

How do you see the role of surgery continuing to evolve with advances in systemic therapy?

Better systemic therapy may open the door to more surgical care. We’re seeing that a little bit with the chemoimmunotherapy protocols, where we are seeing dramatic shrinkage of tumors. We’re seeing more pCRs, and suddenly the question of whether we can make the disease resectable is very real. [Systemic therapy is] opening more opportunities in the oligometastatic space. It’s one thing to kill micrometastatic disease, but sometimes, killing a 5 or 6 cm mass is harder. That combination of good local therapy with good systemic therapy is increasing [the number of people we’re] curing.

As much as I love my radiation oncologists, people love tissue. We’ve realized how informative tissue is in telling us what our next step can be, so that in an otherwise relatively healthy patient, if the choice was to radiate vs resect, a lot of oncologists might favor resection.