Place for Surgery and Poor Prognosis

Transcript; Kohei Shitara, MD: The important aspect of this ARTIST-II study is to confirm in the impact of the combination with S-1 [tegafur-gimeracil-oteracil-potassium]. Previously, we had [only] a capecitabine-oxaliplatin trial, but this is a comparison with a surgery…. We also have a trial suggesting the benefit of S-1 [tegafur-gimeracil-oteracil-potassium] as adjuvant therapy. But now we also have this ARTIST-II trial suggesting that S-1 [tegafur-gimeracil-oteracil-potassium] plus oxaliplatin is better than S-1 [tegafur-gimeracil-oteracil-potassium].

As David mentioned, we also have data [that suggest] that S-1 [tegafur-gimeracil-oteracil-potassium] plus docetaxel improved disease-free survival. So in Japanese guidelines, maybe in the future, S-1 [tegafur-gimeracil-oteracil-potassium] plus docetaxel is recommended. But maybe we should also recommend S-1 [tegafur-gimeracil-oteracil-potassium] plus oxaliplatin based on this ARTIST-II study. This is a very good trial. It was very well controlled. And a D2 gastrectomy. So it’s very similar to the trial in Japan.

Johanna C. Bendell, MD: Does anybody in Japan do FLOT [fluorouracil, leucovorin, oxaliplatin, docetaxel]?

Kohei Shitara, MD: Actually, no.

Johanna C. Bendell, MD: So mostly surgery up front followed by adjuvant...?

Kohei Shitara, MD: Surgery up front. But still, we are very interested in neoadjuvant treatment because to do intensive chemotherapy after a D2 gastrectomy, especially in the older patient, is not so easy. So more by clinical trials, we are going to investigate neoadjuvant maybe in Japan. We are waiting for the PRODIGY trial, which evaluates a neoadjuvant treatment regimen compared with up-front surgery. Also, in Japan, we have a trial to evaluate S-1 [tegafur-gimeracil-oteracil-potassium] plus oxaliplatin as a neoadjuvant treatment compared with up-front surgery in stage III disease.

Johanna C. Bendell, MD: I think those are really important take-home messages here, right? So the esophageal, the proximal GE [gastroesophageal] junction probably have to have radiation incorporated as the component of their treatment. And the high importance of a multidisciplinary specialty center approach for these patients to not necessarily take them straight to surgery but have a discussion around the possibility of neoadjuvant therapy, making sure that these patients are having adequate surgery in a specialty center. And if they’re not having adequate surgery, to make sure that we incorporate some kind of local control into their adjuvant treatment. But certainly FLOT [fluorouracil, leucovorin, oxaliplatin, docetaxel], in my mind—at least in the West—has taken over a lot of the approaches, particularly for the gastric and lower-GE junctional cancers.

Manish A. Shah, MD: Just to add to that, even if you’re HER2-positive, we don’t have the data for trastuzumab in the localized setting.

Johanna C. Bendell, MD: Yes.

Manish A. Shah, MD: We reserve that for metastatic disease. But those studies are ongoing, and that may change practice.

Johanna C. Bendell, MD: I have 1 tricky question that comes up rarely but is interesting. David, let’s say you have a patient with linitis plastica. A young patient, 40 years old, with 3 children has linitis plastica. The patient gets a staging laparoscopy and has no peritoneal disease. What’s your take on surgery there?

David H. Ilson, MD, PhD: Just to make it a little more complicated, if there is a positive cytology, that’s stage IV disease.

Johanna C. Bendell, MD: Yeah.

David H. Ilson, MD, PhD: That patient should not undergo surgery. It’s a whole separate discussion about surgery later, but patients with positive peritoneal cytologies behave like stage IV disease and they should be treated with chemotherapy. So linitis plastica—the problem is getting a negative margin. These patients have a very poor prognosis. Now the paradigm in the US is to give preoperative chemotherapy with FLOT [fluorouracil, leucovorin, oxaliplatin, docetaxel]. The hope would be to achieve a response. We always try to attempt surgery in these patients. The problem is getting a negative margin.

Personally, aside from the patient who has inadequate surgery with poor lymph node harvesting, I would consider that patient for postoperative radiation. But also for patients who have a positive margin after gastrectomy, we would consider postoperative radiation because we can salvage some of those patients. So linitis plastica is a tough call. I think we individualize the treatment. These are patients who we would give up-front chemotherapy to. Those patients are also rarely HER2-positive. They’re bordering on metastatic disease. If I had a HER2-positive linitis plastica patient, I would probably include trastuzumab as part of the chemotherapy. Then I would really individualize the decision about whether surgery could be accomplished. If surgery is done and they have a positive margin, then I would consider postoperative radiation in that patient.

Transcript Edited for Clarity