Physicians Discuss Up-Front Options for Unresectable Stage III NSCLC

Garrett B. Sherwood, MD (Moderator)

Medical Oncologist

Novant Health Cancer Institute - Forsyth

Winston-Salem, NC

CASE SUMMARY

A 63-year-old man presented to his physician with intermittent cough and difficulty breathing on exertion. He had a history of hypothyroidism, which was managed on levothyroxine; and chronic obstructive pulmonary disease (COPD), which was managed on inhalers. He recently quit smoking and has a 40-pack-year history. His ECOG performance status was 1. Complete blood count, chemistries, and creatinine were within normal limits.

A chest CT scan showed a 3.1-cm spiculated left upper lobe (LUL) mass and 2 enlarged left mediastinal lymph nodes (stations 4L and 7), measuring 2.5 cm and 1.7 cm, as well as moderate emphysema. A PET scan confirmed lung lesion and mediastinal lymphadenopathy without evidence of distant metastases. His brain MRI was negative. Pulmonary function tests showed a forced expiratory volume of 1.2 and a diffusing capacity of the lungs for carbon monoxide of 35%.

Bronchoscopy with transbronchial lung biopsy of LUL mass and lymph node sampling via endobronchial ultrasound revealed adenocarcinoma at primary site, with positive nodes in stations 4L and 7. His cancer staging was T2aN2M0, stage IIIA.

DISCUSSION QUESTION

• What approach to biopsy is appropriate for a patient like this?

GARRETT B. SHERWOOD, MD: What do you think about the choice of biopsy? What would you do if this patient had no sufficient sampling from the lymph nodes at the time of bronchoscopy?

JONATHAN KRAUT, MD: Because of the location of the lymph nodes, navigational bronchoscopy or endobronchial ultrasound [EBUS] are completely suitable. It’s been demonstrated by enough data that it is equal to a traditional mediastinoscopy. It’s a reasonable approach. We would refer to the pulmonary department for an EBUS, traditional bronchoscopy, or even a navigational one.

SHERWOOD: If you’re practicing in a situation where access to EBUS is limited or the primary care physician worked this up and did a CT-guided biopsy of the primary mass for lymph nodes that haven’t been pathologically confirmed to be malignant, what criteria do you use to decide when to go back and recommend another biopsy? Or in the interest of simplifying the patient’s evaluation, when to not send them back for another biopsy but just clinically stage them as stage III.

KRAUT: Mediastinoscopy is a great tool, and we still use it often. If they couldn’t get to it with bronchoscopy, then traditional mediastinoscopy is a very useful tool to stage the patient.

SHERWOOD: What do you do in your practice if you happen upon a patient who you suspect has pathologic involvement of lymph nodes but that wasn’t proven with their biopsy?

MAURIZIO BENDANDI, MD: This would be discussed in the tumor board…and maybe a collegial decision would be made. Sometimes patients have different outcomes based on the feelings of the group.

ARUN BHANDARI, MD: In our hospital, we have a multidisciplinary tumor board, and most of the EBUS and bronchoscopies are done by the thoracic surgeon, especially in such an area where it’s stage III or stage II. Our thoracic surgeon will decide. They’re pretty good with EBUS and bronchoscopy.

SUKHMANI GILL, MD: I work at Pardee Hospital in Hendersonville, [North Carolina], so we don’t have our own thoracic surgeon, but we will send patients to Greenville [Memorial Hospital in South Carolina]. Our pulmonologists are good, but if they can’t get to it, they will refer the patient. So by the time they come to me, we’ve already had this definitively handled. Even though we don’t have our own thoracic surgeon, there is usually cohesive and good communication.

SHERWOOD: Great, thanks for sharing. As medical oncologists…we [usually] want more tissue for biomarker testing.

DISCUSSION QUESTION:

• What was your reasoning for the up-front option you would choose?

SHERWOOD: I selected concurrent chemotherapy with radiation. I am very intrigued by some of the neoadjuvant chemoimmunotherapy data, and I believe they are going to be a paradigm-shifting option down the road. I want to see a little more of the [disease-free survival and overall survival] data mature. But as I work very closely with my surgical colleagues, I’ve learned that these cases do [have] an element of trickiness to them. Can someone who selected neoadjuvant chemoimmunotherapy talk us through their thought process?

BHANDARI: In the tumor board, it’s a decision between the medical oncologist, radiation oncologist, and the surgeon. The surgeon can say, “I’m comfortable taking it out,” or “I don’t think it’s resectable.” Then concurrent chemoradiation is given. But it is a discussion had by the multidisciplinary tumor board. I picked neoadjuvant chemotherapy and immunotherapy because I’m confident the thoracic surgeon will probably agree with my opinion.

BENDANDI: I reluctantly picked neoadjuvant chemotherapy with or without immunotherapy, followed by surgery. I would say it should not be followed by surgery because the patient is deemed not to be a good surgical candidate. [At my hospital], we don’t have [radiation therapy], so concurrent is rarely feasible. As for sequential, I hope that the future will be neoadjuvant chemotherapy plus immunotherapy, followed by surgery, [though] probably not in this case.

CHARLES KUZMA, MD: I don’t think this patient has macroscopic N2 disease. That’s usually not the ideal candidate for surgery. We identified that this patient, based on his pulmonary function, was never going to be a surgical candidate. For all those reasons, I chose concurrent chemoradiotherapy.

SHERWOOD: Those are all great points. N2 disease is a subgroup I’m going to be paying a lot of attention to when I’m looking at the CheckMate 816 study [NCT02998528]. There’s a whole host of neoadjuvant immunotherapy alone and chemoimmunotherapy studies, which will be a lot for medical oncologists, surgeons, and radiation oncologists to sift through over the next few years.

KUZMA: I don’t think a patient like this would have been eligible for CheckMate 816.

SHERWOOD: You’re probably correct, based on those [pulmonary function tests]. I would imagine they would say that even if the patient had a complete response on imaging, that would be someone who would not do well with an operation. Dr Kraut, you’re the only one here with experience operating after neoadjuvant chemoimmunotherapy. What’s been your experience?

KRAUT: We’ve had very good outcomes with our patients. It’s been a little more challenging in the interval from completion of treatment to surgery. Those patients have more desmoplastic changes, particularly around the lymph nodes, and the lymph nodes are around arteries and the bronchus. It’s more [time] from a dissection standpoint, but it has not added a lot more time. If you look at some of the data that are out there, [it can be] anywhere between 30 to 45 minutes more due to the surgical complexity, but we’ve not [seen] that. Most of our patients have done very well. We [perform] them robotically; I think we’ve done all but 8 or 9 robotically. It’s a little more complex because of the scarring and the desmoplastic changes, but overall, it’s not been anything like when we used to see patients who had chemoradiation to the hilum.

SHERWOOD: Great, thanks for sharing.

CASE UPDATE

In this patient, the results of molecular testing show negative results for driver oncogenes in EGFR, ROS1, BRAF, ALK, RET, MET, ERBB2, NTRK, and KRAS. His PD-L1 expression level is 1%.

SHERWOOD: Does this change anyone’s thoughts about what they would do for this patient? Not so much for me. I would probably still be recommending concurrent chemoradiotherapy.

BENDANDI: I would switch to chemotherapy plus sequential radiotherapy unless I can obtain it concomitantly. But the radiotherapy must be outside the VA [Veterans Affairs hospital].

SHERWOOD: Yes. I trained at a VA facility, and it was always a little problematic to refer someone outside the VA for radiation therapy, and to time concurrent chemotherapy with that, too. I recognize that conundrum.