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Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)

 

The Great Debate: Should Surgery be the "Standard of Care" for Stage IIIA NSCLC with Mediastinal Nodes?
Author
Howard (Jack) West, MD

It's over, and I won (did you doubt me?). As I mentioned in a recent prior post, today I spoke at the Eighth International Lung Cancer Congress, where I was assigned the topic of speaking in favor of chemo/radiation as the more appropriate standard of care, with the opposing view, that surgery is the standard, taken by the esteemed Dr. Stephen Swisher, thoracic surgeon (and actually Chair of the Department) at the MD Anderson Cancer Center in Houston.

Now in truth, we didn't differ very much in our perspectives. One key point we agreed on completely is that the stage of IIIA N2 NSCLC is a very heterogeneous group, ranging from some patients with just microscopic involvement of a single lymph node in the mediastinum (mid-chest, between the lungs) to multiple lymph nodes at multiple areas of the mediastinum that are enlarged and even bulky (more than about 2 or definitely 3 cm). In fact, within that range, outcomes are very different, with the group who have a single area of non-enlarged lymph nodes that have cancer involvement just at the microscopic level having a much better prognosis than those with enlarged nodes or with more than one mediastinal area involved:

Andre figure range of IIIA (Click to enlarge)

Because this stage covers a huge range of tumor bulk and extent of nodes involved, it really doesn't make sense to expect that there should be a "one size fits all" treatment approach for IIIA N2 NSCLC, the group most on the cusp of surgery or not. Dr. Swisher focused on the point that some patients with non-bulky disease and a very good performance status (good health, few other medical problems) are probably best served by an aggressive treatment approach that includes surgery. His focus was on a clinical trial, Intergroup 0139, that I've described in a prior post (abstract here). In this trial, 439 patients with stage IIIA N2 NSCLC were randomized to receive chemo and radiation as either pre-surgical induction therapy, sometimes followed by more chemo, or full chemo and radiation with no surgery:

ALbain Int 0139 schema

Essentially, this trial showed that both groups had the same survival. In the surgical group, they had more early deaths from treatment-related adverse effects, but if you got through the early part, there was a good hint that you might do better than chemo/RT alone after several years. The group getting chemoradiation followed by surgery had a higher progression-free survival, but the overall survival benefit that might have been seen by surgery was eradicated by an increased risk of dying from treatment, particularly early on:

INT 0139 curves

In fact, after sifting through the data, the investigators found that much of the problem was that about 1/4 of the people who had pneumonectomies (entire lung removed at surgery) died within a few weeks of surgery. In contrast, the people who just had a lobectomy tended to do well. This led them to do a fancy analysis where they tried to match patients on the surgery arm to similar patients (matched by age, sex, performance status, and tumor stage, but not nodal stage, which is a real shortcoming) on the chemoradiation arm. When they did that and compared the groups, it looks like the patients who needed a lobectomy did better with surgery, and the patients who needed a pneumonectomy did better with chemoradiation:

INT0139 lobe INT 0139 pneumonectomy

Well, that's pretty impressive. I'll say that there are some flaws in the analysis, but it's hard to argue against the view that there are patients with stage IIIA N2 disease who are likely best served by a very aggressive approach that includes surgery. So I didn't -- I conceded that point. But I still won the debate, and that was because my conclusion on all of this was a little different. I need to close now, but tomorrow I'll give the counterpoint against surgery, which in truth agreed closely with Dr. Swisher's perspective, but it just emphasized the other side of the coin. I'll provide that perspective tomorrow. Right now, I'm in Hawaii, and I'm working on a computer, and it's time to go.

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