How Neoadjuvant Therapy Beats Postoperative Chemotherapy

Dr Mark Kris discusses the history of and considerations for using neoadjuvant therapy.
https://www.medscape.com/viewarticle/how-neoadjuvant-therapy-beats-postoperative-chemotherapy-2025a10001oy?src=soc_yt

--TRANSCRIPT--
Hello. It's Mark Kris, from Memorial Sloan Kettering. I recently returned from a meeting of thoracic oncology physicians in California, and there was a large amount of discussion about perioperative therapy.

I have to say that, of all the areas of uncertainty right now, it is probably in that area. It is a time, though, of growing consensus that neoadjuvant therapy has so many advantages that it really makes sense and needs to be on the table for everybody. I think there's agreement on that.

What I'd like to do is talk a little bit about the history here. Why do you give neoadjuvant therapy? The history here at my institution is that our very talented surgeons would do complete resections of patients with bulky mediastinal disease. They would accomplish a complete resection; however, patients would succumb to metastatic disease.

The reason for the chemotherapy or other systemic therapy would be to control systemic disease. When you look at all the results of neoadjuvant therapy, you see that's where the advantage of it is. It improves progression-free and overall survival by controlling metastatic disease.

There's really no proof that chemotherapy facilitates surgery, allows fewer surgeries, or somehow improves the control. It probably doesn't do that. It controls metastatic disease.

What got me thinking about this after that discussion was a paper in The New England Journal of Medicine about the use of perioperative chemotherapy and radiation in patients with locally advanced gastric cancer. They saw that adding radiation did not improve either progression-free or overall survival, while it did improve both pathologic complete response rate and downstaging.

Years ago, these issues had been looked at in lung cancer. In truth, what you would expect is that giving another local modality would not improve those important outcomes of survival, but it would change some other outcomes, such as the pathologic complete response rate and the downstaging.

My colleague, Matt Hellmann, reviewed the literature many years ago, and he saw that when you add radiation, yes — you increase the pathologic complete response rate, but you don't increase overall survival or event-free survival. To me, it's obvious because you can't expect a local modality to improve the control of micrometastatic disease. A complete resection completely controls local disease, so you don't need radiation on top of it. It's two local modalities.

Downstaging is very tricky. To be honest, you can't be sure that somebody is truly downstaged unless you know for sure that the lymph node that you're examining had cancer before the neoadjuvant therapy and didn't afterward. Not having it afterward, you can't be sure that it was there in the first place. That, too, has never been shown in lung cancer and is not shown here in gastric cancer either.

Some points. First, in lung cancer, there is a huge role for neoadjuvant therapy. There's every reason to give it. It's easier for the patient; you know if it's working; and it gives you, at the time of surgery, really important information about that outcome of the patient.

Information from pathologic complete response is the information that comes after a systemic therapy. It's systemic therapy that has been associated with overall improvements and overall and event-free survival, not necessarily the pathologic complete response if indeed you've added in a second modality.

Now, with the accompanying literature, particularly for melanoma, that the use of neoadjuvant therapy provides added benefits over the same drug therapy given postoperatively, I think there is more and more evidence that neoadjuvant therapy is the way to go.

I urge you to carefully look at the papers, and please carefully consider neoadjuvant therapy in any patient with locally advanced disease. Always have it on the table. Again, it's not perfect for every patient, and there are always individual choices that need to be made. For the first therapy to turn to in patients who are driver-negative, neoadjuvant chemotherapy or chemoradiotherapy is the way to go.

Transcript in its entirety can be found by clicking here:
https://www.medscape.com/viewarticle/how-neoadjuvant-therapy-beats-postoperative-chemotherapy-2025a10001oy?src=soc_yt