Clinical Cases in Lung Cancer - Episode 13

Case 3: 63-Year-Old Man With Unresectable Stage IIIA NSCLC

Brendon M. Stiles, MD: This is case 3. This is a 63-year-old gentleman who presented to his internist with intermittent cough and some dyspnea on exertion. He has hyperlipidemia, hypothyroidism. His main comorbidity is COPD, which is managed with inhalers. He recently quit smoking, although he has a 40-pack-year history. He presented with intermittent wheezing and the shortness of breath as I mentioned, but otherwise negative. His performance status is a 1 based largely upon the pulmonary disease. The patient’s laboratory test results were normal. A chest CT scan was obtained, which demonstrated a suspicious 3.1-cm spiculated right upper lobe mass. There were also 2 enlarged right mediastinal lymph nodes, measuring 2.5 cm and 1.7 cm, the suggestion of relatively bulky disease, as well as moderate emphysema. The PET scan confirmed the lung lesion is PET avid and also the mediastinal lymphadenopathy, but was without evidence of distant metastases or other lymph node disease. A brain MRI was obtained, which was negative. The patient’s pulmonary function was fairly poor with an FEV1 of 1.2 liters and a DLCO of just 35%.

Mark Socinski, MD: Brendon, give us your thoughts in terms of an initial staging approach in this patient. You reviewed the radiographic findings. Let’s assume you’re seeing this patient in your clinic for the first time, how do you go about getting a diagnosis and combine that with the right staging? Would you favor one procedure over another, or how do you think about this?

Brendon M. Stiles, MD: Good question. We probably, like most of you, like to go after what we think is the highest stage disease first. Rather than doing a lung biopsy, I would start with staging of the mediastinal nodes. I think it’s dealer’s choice in terms of EBUS versus mediastinoscopy, but I think most have moved away from mediastinoscopy and would prefer EBUS, particularly here in this setting of bulky mediastinal nodal disease. Mediastinoscopy may have an advantage of being better at checking the N3 disease, and I do think it’s an important point for somebody with bulky N2 disease, if you’re considering resection, to rule out N3 disease. I try to make a good effort to get not only the N2 stations, whether there’s 1 N2 station or multiple stations, but also to check some of the N3 nodes.

Mark Socinski, MD: In the setting with very bulky nodes, I assume the false negative rate of EBUS is fairly low, correct?

Brendon M. Stiles, MD: Right, it should be less than 10%. Typically we can get enough for diagnosis and for molecular from there if people thought that was important as well.

Mark Socinski, MD: In knowing that EBUS does have some operator dependency aspects to it, if you came up negative on an EBUS, is this a patient you would do a mediastinoscopy on following that?

Brendon M. Stiles, MD: Yes, that’s a great point. This is the classic case where I would not accept a negative EBUS, nor should anyone else in the community. He’s got pretty clear-cut evidence of regional lymph node disease or mediastinal lymph node disease, so a negative EBUS here should be followed with a mediastinoscopy.

Mark Socinski, MD: Let me ask, what I think, and I’m not a surgeon, but what I think is difficult to answer is what are the criteria for resectability? Then, more importantly, this term unresectable. Does unresectable mean they’re technically not resectable, or there is not sufficient evidence that they should be resected?

Brendon M. Stiles, MD: I think the latter is true, and I think you and I have talked about this before. Probably anything can be resected, and the real question to surgeons is should you or should you not. It’s a tough question. I think bulky N2 disease should give people pause. Yes, I’ve resected the occasional patient with bulky N2 disease, and particularly if we think we can do a lobectomy rather than a pneumonectomy. But that’s often the equivalent, as you all know, of systemic disease. So bulky N2 disease, multistation N2 disease, disease requiring a pneumonectomy, for me often fall into the I-probably-shouldn’t-resect side, even if I thought it was resectable disease.

Mark Socinski, MD: My training was in this group of patients, and again to your point, there’s a great deal of heterogeneity in this population of stage III patients. The surgeon’s stage IIIA may be different than a radiation or a medical oncologist’s stage IIIA. I’ve always been taught that the decision about surgery should be made up front, and that this strategy of saying, “Well, let’s give them some induction therapy, see how they do, reassess for surgery down the road,” is kind of a treacherous path to take because we really don’t have necessarily a good way to assess people that way. Is that your thinking, or educate me on that.

Brendon M. Stiles, MD: I totally agree with you. I think it’s a hard decision to make after the fact, and this should be made up front based on the discussion with the multidisciplinary team, what your radiation oncologist thinks, what your oncologist thinks, what the patient thinks, because there’s multiple reasonable ways to approach this. It’s a little bit of a fallacy to think that chemotherapy can take an unresectable patient and make him or her resectable. When you can make this decision up front, I always think it’s an easier course for the patient.

Mark Socinski, MD: I think that’s a good point. I have seen a number of patients seeking second opinions who have started on therapy, and the assumption is that some sort of induction therapy with standard chemotherapy is going to take a patient who clearly unresectable disease and they’re going to make them all of a sudden resectable. Or if you really think you need a pneumonectomy to start with, you’re going to downstage them so much that you can do a lobectomy, and I don’t know that we have any evidence to support that that would be the right thing to do.

Brendon M. Stiles, MD: Yes, I agree, it’s pretty unlikely that you would have that kind of response with chemotherapy.

Mark Socinski, MD: Yes. And then, we’ll talk a little bit about this when we get further along in the case, but obviously we’ve had a change in the standard of care with the incorporation of immunotherapy as we alluded to before. Anything in that data set that changes, say, what your thinking was 5 years ago? Has it changed given the PACIFIC data in your mind in any way?

Brendon M. Stiles, MD: It’s a great question. We’ve got great options for stage IIIA that we’re not going to resect now, and in the past that might not have looked as good as the PACIFIC arms. I think if you’re in a place where the surgery, where you’re worried about it, I think it’s perfectly good for III and IIIA patients to get chemoradiation and then durvalumab. For me, as immunotherapy keeps creeping earlier and earlier, I think that might be competitive. Certainly to roll the dice for the IIIB or IIIC days, I think should be largely behind us.

Mark Socinski, MD: Institutions tend to be either more aggressive or less aggressive in stage III disease. I want to ask Ed and Tim, what’s it like at Levine Cancer Institute? Are the surgeons particularly aggressive in this stage III setting or less aggressive? And then the same question to Tim.

Edward Kim, MD: I’ve actually found our surgical colleagues to be extremely reasonable, even when I was at The University of Texas MD Anderson Cancer Center with Steve Swisher, and that group. They liked induction, but just as Brendon said, I don’t believe in downstaging in lung cancer. It just doesn’t happen. You’re either resectable and you’re given the chemotherapy up front, or you’re unresectable.

Mark Socinski, MD: I think that’s an important message to our audience. Tim, your situation there at your institution?

Tim Kruser, MD: I would echo a lot of Brendon’s points, and I think my surgeons follow a lot of the paradigms he outlined in that it’s not whether they can be resected, it’s whether they should. When you’re getting to the point where you’re trying to convince yourself that downstaging with chemotherapy is going to turn someone from unresectable into resectable, you’re probably talking about the patient who has such a high risk of distant metastatic disease, that you probably shouldn’t be operating. And our surgeons are very thoughtful and reasonable men in that same way.

Transcript edited for clarity.