12 hours ago
It's Complicated: Surgery and Lung Cancer Care
This transcript has been edited for clarity.
Hello. It's Mark Kris from Memorial Sloan Kettering, continuing my little series on the initial treatment of patients with lung cancers. In the earlier discussions, we talked about people with metastatic disease. I'd like to switch today to talking about people who are candidates for surgery.
The two operant terms here are operable and resectable. Operable means that the patient is medically fit to have an operation and to undergo the extent of surgery needed for a complete resection. Resectable means that, in the opinion of the thoracic surgeon who will be performing the surgery, R0 resection is likely to be achieved.
Again, these things are not perfect. Experience guides many of our decisions here, and the operative decision is made by many different folks. The surgery decision really needs to be made by a surgeon. The truth is that the question of resectability comes from the surgeon at your institution, in your multidisciplinary tumor board.
What are the stages we're talking about? Looking at the trials of perioperative therapies, the stages looked at are IB (tumors greater than 4 cm, regardless of nodal status) up to IIIB (larger primary tumors with N2 nodes). N3 nodes are a different discussion, which we'll hopefully have later on.
I think I personally am unbelievably struck by the amount of data and the absolute consistency of data about the use of neoadjuvant therapy in patients who do not have a driver. That's the first group I'd like to address.
It is critical to get sufficient tissue to make sure that there are no drivers present. If you have a driver, particularly EGFR and ALK , it sends you in a different direction for decision making. Also, if you're following the package insert, for example, you need to show that the patients are EGFR and ALK negative. To do that, you really should do next-generation sequencing in 2025. It has to be done on tissue.
The data from using blood in these situations show that less than [about] one in five of the mutations are detected in blood in these earlier-stage patients. You must have tissue. Obviously, if you have a positive blood test, that's great. You can use it. If it's negative, though, you must have tissue. You have to get the tissue, you have to get the answer, and you have to get it quickly. It's not an easy situation, and we can talk about that.
I think the data are very, very clear in the nine trials now. There are nine randomized trials that have been reported, and every single one shows an improvement in disease-free survival by giving neoadjuvant therapy with chemotherapy and a checkpoint inhibitor.
I'm struck by the consistency of the trials, by the huge amount of data, and I think that makes this the standard of care today in patients that are both operable and resectable.
What about the discussions that go on at our tumor boards about the need for immediate surgery, particularly for sick patients with IB and II disease?
Well, I have to say that there are virtually no data for the patient sitting in your office, saying that immediate surgery followed by adjuvant therapy is as good, or better than, the neoadjuvant approach. Frankly, there probably is never going to be a trial that answers that.
When you look at the trials of where people have proposed to do adjuvant therapy, up to one-third of the patients, or more, never get the adjuvant therapy. It's really an apples-and-oranges comparison here. The data just do not exist and I think are unlikely to exist just by the nature of the problems.
For people who have neoadjuvant therapy, there are two groups now as well. There are patients who have a major response, particularly a pathologic complete response or no pathologic response, and there are patients who don't.
I think for those who don't, the way forward is clear. You need an alternative therapy. I personally would advise not to give a component of the neoadjuvant program that was truly unsuccessful, particularly for folks who have a large amount of remaining disease in the resection specimen.
For people with no pathologic response or a pathologic complete response, the question there comes whether to give perioperative therapy, generally the checkpoint inhibitor, after or not. The data here are, again, not going to give you the answer.
The trial of nivolumab — not followed by a year of nivolumab after surgery — showed very, very good results and really comparable to those results. The FDA has clearly pointed out that the data supporting the use of the additional year of therapy with the checkpoint inhibitor are not proven. There is toxicity. In adjuvant situations, the data are not particularly impressive.
I do want to point out the need for consideration of postoperative therapy with radiation if you have N2 disease. When you look at the recurrences noted in the neoadjuvant and adjuvant trials, now with better systemic therapy, the recurrences are in the chest.
We must think about improving control in the chest. Frankly, the only modality we have today to do that is radiation, and it's most proven for N2 disease. I do think it's very, very important for people with N2 disease to get a radiation oncologist in the treatment planning group to see if there is a role for radiation in those patients.
To summarize, I think for patients who don't have a driver and are operable and resectable, neoadjuvant is the way to go. What you do afterward is difficult for people with a major pathologic response. You can make a good case for not giving any additional therapy. There are FDA-approved regimens to give additional therapy of the same drugs.
For people who clearly progress, you need to think about what other alternatives there are, both local and systemic.
