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No Evidence of Disease—No Need for the Knife?
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Released: May 12, 2025

Expiration: May 11, 2026

John Marshall
John Marshall, MD
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No Evidence of Disease—No Need for the Knife?

 

John Marshall, MD: John Marshall for Oncology Unscripted. Let's talk a little science and cancer medicine. I’m gonna come at you from a little bit of a different angle. Yep. A GI cancer angle, but a little bit different.

 

We have long felt in order to cure GI cancers, we had to do surgery, that it was the only way to ultimately cure people. But we all know that when we do neoadjuvant something could be chemo chemoradiation. we operate. A certain sub portion of the patients have no evidence of disease in their pathology specimen, and we sort of say, we just put somebody through a big operation gastrectomy, esophagectomy, could be a Whipple, could be a rectal surgery that they actually didn't probably need or benefit from, but we had no way of determining that until we did surgery. And so, as you know as well, there's increasingly neoadjuvant therapies for a bunch of different cancers. People are having good clinical responses where after the neoadjuvant treatment, by scope or by scan, and now by new blood testing, we can't find evidence of disease. We're torn about whether we can simply watch and wait that patient and see their cancer comes back, or do we have to operate anyway.

 

And there's a new paper that just came out, that I used actually in last week's tumor board here at Georgetown about watchful waiting in esophageal cancer versus surgery. So basic story, neoadjuvant treatment, everybody got it. If you had a complete clinical response, you were randomized, so not done in the United States. We'd never pull it off here, were observed for clinical recurrence and not operated on unless they had a recurrence. The other half were operated on, and then they looked for survival. And believe it or not, there was no difference survival outcome. So, some of those people avoided a surgery that they didn't need in the end and no impact on the survival. Now we still need to do better because it's still pretty crummy survival in this group of patients whether you had surgery or not, but still no difference.

 

 In rectal cancers, we are increasingly not doing surgery. I've got a 35-year-old woman who had a very good initial response, a very good response to chemoradiation, no clinical evidence of disease. Doesn't want a colon surgery and a permanent ostomy, as you might imagine, at 35 years of age. And we've been doing watchful waiting, including doing MRD testing, and so far, nine months with no evidence of disease. And I'm sure all of you have patients like that.

 

We are also, of course, doing this in pancreatic cancer. And the reason for obvious reasons is that it's a difficult operation. A lot of people don't want the operation. More often, it's because of where the tumor is. It might be grabbing onto a blood vessel that the surgeon doesn't really think they can get around. Or it might be that the risk of the surgery is just too great for that individual patient. So, we are doing neoadjuvant treatment. We are doing radiation, sometimes maintenance after, sometimes not, and observing. And you, like me, have had over your career some patients whose tumors never regrew and maybe just maybe got out of the need for surgery. So, this then brings up. What are the right treatments? How do you pick which patients should have surgery, which you're not. The current neoadjuvant study that's in the cooperative groups here in the United States is surgery first versus chemoradiation first, followed by surgery. Should we begin thinking about a no surgical arm in this group of patients? As our drugs are getting better, as we are learning more about targeting RAS and BRCA and the other molecular targets that we have. Will we get to a place where we can actually increasingly avoid what is fairly morbid surgery? Let's particularly think about pancreas cancer, in this regard, because remember. It's very good at sowing early seeds. It's very good at metastasizing early, and in fact, only one out of 10 is found with resectable pancreatic cancer at initial diagnosis most have already spread. So, the value of that resection, don't get me wrong, it is the way we cure people, but the relative value of that resection in the global scope of pancreatic cancer is increasingly in question. So, as we pick therapies, highest response rate, three drug combinations, 5-FU, irinotecan, liposomal irinotecan, and oxaliplatin. Highest response rate, highest survival in the books for metastatic disease. As we use regimens like that in the neoadjuvant setting, as we add to those regimens with new targeted therapies, I do think what we will see is more and more opportunities for observation in that patient population.

 

We held a think tank here at Georgetown back in the fall where we invited people from all over the country who were experts in this field to think about this issue and the consensus among, what I think are some of the smartest people in the world around this subject was, that yes, indeed, the improvement of chemotherapy, the advent of precision medicine, the increasing role of immunotherapy in this space will get us to a place where, in fact, we are curing more and more people with pancreatic cancer. We need to get there. We need to make the progress. We need enrollment in clinical trials, but I believe we are going to see it. I believe we're going to see progress in 2025 and 2026. So, stay tuned for more positive papers, more positive data in the world of GI cancers and in pancreatic cancer, specifically.

 

John Marshall for Oncology Unscripted.