SLIDES & TRANSCRIPTS
Tuesday, June 19

SURGERY SECTION - HISTORICAL PERSPECTIVE OF TRIALS EVALUATING LIMITED VS. EXTENSIVE RESECTION OF NSCLC

Valerie Rusch, MD

DR. RUSCH: Thank you, Scott.

So continuing on the theme of the afternoon here, I had received neither the slides nor the text, however, these are my slides, and I'll try and fill in what I think Bob wanted to say had he been here.
The purpose of this initial brief presentation is just to provide the historical background which will serve as a platform for the other presenters to describe what is more recent work with respect to the pros and cons of limited resection for early stage lung cancer. Of course this is extremely familiar material to all of the surgeons who are here today, so I'll try to be mercifully brief about it.
What are the issues in terms of limited resection versus what has become the standard of care for small lung cancers, T1 lung cancers? Well, they are the morbidity and mortality of resection; the risk of local recurrence; and whether or not there is adifference in overall survival between limited resection and lobectomy.

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Now there are a number of retrospective studies going back over the past 20 years which I have tried to list here briefly. As you can see, they really evaluate relatively small numbers of patients in a retrospective manner, and the endpoints of the studies or the analyses involve a variety of issues, some focusing on survival, and some focusing on local recurrence, some of them finding no differences in those endpoints, and some of them suggesting that there might be either worse survival or increased recurrence for a limited resection.

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To go back to some older information from the late 1980s, from my own institution at Memorial, this is reported by Nile Martini. He reviewed the experience with almost 600 cases, which were fairly equally divided between T1 and T2 lesions.

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Most of these patients did have a lobectomy, and the patients who had limited resection, either a wedge resection or a segmentectomy probably had that done based on their pulmonary risk for a standard resection.

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You can see that the survival was related to tumor size. So really almost 100% survival for patients who had less than a centimeter size lesions. A significant difference in survival was noted between those lesions and the somewhat larger T1 and then T2 lesions.

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There was a higher recurrence rate, and I believe this is by multivariate analysis if I remember correctly, recurrence rate according to whether there was a limited resection or a lobectomy performed.

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There also appeared to be a difference in survival.

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Well, the deficiencies of course of these various studies, including the one that I have shown you from Memorial is that they are retrospective studies. Relatively small numbers of patients were evaluated in these studies. And there are marked differences in the parameters that are measured, in some cases recurrence, in some cases survival. In some reports all deaths are analyzed, and in others cancer-related deaths are analyzed, and so forth.

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Now as far as I know, the only prospective trial which has really examined this issue of whether we should be doing lesser resections, as opposed to lobectomies for earlier stage lesions is the lung cancer study group trial, LCSG Trial 821. And in this trial, patients who were either known or thought to have lung cancer, and thought clinically to have a T1 N0 lesion were taken to the operating room. They did not need to have a preoperative pathology diagnosis. They were then diagnosed, or the diagnosis was confirmed in the operating room, and they underwent careful intraoperative staging. Once it had been determined that they were in fact N0 based on frozen sections, those patients were randomized to undergo either a limited resection, wedge or segment, or a lobectomy. In addition to the endpoints of survival and recurrence, patients were also assessed for the impact of the resection on their pulmonary function.

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Because there was no absolute need to obtain a pathological diagnosis preoperatively, there were 771 patients registered to this trial, but only 276 randomized. You can see here the reasons for non-randomization. Either the patients turned out not to have a true T1 N0 lesion, or they had other diagnoses intraoperatively.

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So in the net result, there are 125 patients randomized to undergo lobectomy, 122 to a limited resection. Most of those limited resections, but by no means all of them were segmentectomies. There was no difference in the stratification variables. And there was no difference between the two arms of the trial in morbidity and mortality.

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There was a significant difference in local regional recurrence and death, as shown here, although it was really death with cancer, as opposed to death of all causes. But certainly a higher local recurrence rate with the limited resection.

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There was a difference in pulmonary function in the early post-operative period, within the first six months, but that became less significant as time went on. So that as patients got out to a year or a year and a half post-operatively the differences, as measured by spirometry at least, were not appreciable.

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So the conclusions from this trial were that wedge or segmentectomy were acceptable operations for individuals who would be considered high risk from the standpoint of their overall medical condition. One has to be very careful about the selection of these patients, and again, we are not talking predominantly about the patients who are under discussion today. These patients are the 2-3-centimeter types of lesions. Lobectomy, at least for the standard T1 N0 remains the standard operation.

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Now I just wanted to finish up by pointing out a couple of things. The LCSG had a natural history registry for T1 N0s. That was distinct from the study that I have just presented. This was really quite a nice registry in that there were 907 patients. So a very large number of patients who were carefully staged intraoperatively, and then followed for more than five years. One of the things that we learned from this registry was the frequency of new, non-pulmonary cancers. These developed at a constant rate of 5.2%, and new pulmonary cancers were most common after five years.

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This has also been true in our institutional data for Memorial, as shown here. Again, the same study that I showed you earlier, reported by Nile Martini, showing that there is a very significant risk of second primary cancers, which are mostly second primary lung cancers as time goes on.
So I think as we go forth with our discussions this afternoon about how to manage these patients, particularly these very early lesions that have a very high chance of cure with whatever local modality we choose to offer them, we have to bear this mind. We are talking about not only the immediate management, but what we can do for these patients long-term.
Because if we potentially offer them some kind of intervention up front that is likely to limit their options later on, these are patients who are potentially cured from their very small tumors, and will have second primary tumors. And we need to consider leaving options open for them in terms of treatment at a later date.
This has been less of an issue when most patients are diagnosed with larger or more locally advanced tumors, and don't live as long. But I think that we have to look at what will be possible, what is the future for these patients, not just five years down the pike, but 10, 15, or 20?
So I think I'll stop at that point, and let you go on to the other speakers.

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