Transcript: Johanna C. Bendell, MD: Thinking about locally advanced gastric cancer, thinking about potential surgery options, I get so many questions. How do you treat an esophageal patient versus a GE [gastroesophageal] junctional patient versus a gastric cancer patient? Should I be giving chemotherapy? Should I be giving chemoradiotherapy? Should it be neoadjuvant? Should it be adjuvant? How do we make sense of all this? David, what is your approach?

David H. Ilson, MD, PhD: I think the take-home message is that adjuvant or neoadjuvant treatment improves outcomes. We know that surgery alone for T3 or node-positive disease is no longer acceptable. I think systemic therapy plays a role in all these diseases, and the issue is, what’s the contribution of radiation therapy? For tumors of the esophagus and the more proximal GE junction, we have anatomic considerations. We know historically and even from data from randomized trials that patients who undergo surgery have fairly high rates of inability to operate. The curative resection rates are in the 60% range, even some contemporary surgical arms. We saw 1600 patients in 2 recent large British studies that reported R0 resection rates in the 60s.

To me systemic therapy and chemotherapy are important for tumors of the esophagus and GE junction, given the risk of inability to operate and also the fairly high rates of local recurrence. To me, those patients should get chemotherapy plus radiation. The standard was really defined by the CROSS trial in the Netherlands, which gave a relatively simple chemotherapy regimen, weekly carboplatin-paclitaxel, and radiation, followed by surgery. This trial achieved R0 resection rates in the high-80%-to-90% range and reduced local recurrence. Even a brief exposure to chemotherapy reduced metastatic disease and improved survival. I think that for esophagus and the more proximal GE junction tumors, that’s the approach we endorse in the United States.

In terms of neoadjuvant chemotherapy, that was really established as a standard of care in Britain. The MAGIC trial looking at perioperative ECF [epirubicin, cisplatin, fluorouracil] versus surgery alone improved survival. That really became the standard in the United Kingdom and the West—to give perioperative chemotherapy with ECF [epirubicin, cisplatin, fluorouracil] with surgery. Even in that trial, with chemotherapy alone, you didn’t get enhanced rates of resection, and the role of radiation in the gastric cancers was not well defined.

Recent studies have looked at whether adding radiation to perioperative chemotherapy improves outcomes. The CRITICS trial of over 700 patients treated in the Netherlands, Sweden, and Denmark randomized patients to perioperative chemotherapy alone with or without the addition of radiation and showed no survival benefit. So for GE junction gastric cancers, getting perioperative chemotherapy and adding radiation postoperatively did not show a benefit. Kohei can comment on this. You see mostly gastric cancers, and given the screening and potentially earlier stage, up-front surgery is the preferred approach, and adjuvant chemotherapy is the preferred approach in Japan.

Kohei Shitara, MD: Yeah. Actually, D2 gastrectomy is a standard procedure from the older days, but the surgical procedure has not changed. They did the D3 gastrectomy, but it did not improve outcomes. D2 gastrectomy is still the standard.

Johanna C. Bendell, MD: Can you tell us what a D2 resection is? This is actually very important. When you go way back to when we looked at the Intergroup 0116 study, we saw that the surgeries were very variable depending on the surgeon. Tell us a little about, especially with the Japanese experience, those different surgeries?

Kohei Shitara, MD: Actually, it is very difficult to explain. It was defined in the Japanese guideline because D2 gastrectomy is different in each region. If the patient had a proximal tumor, this should be dissected different from distant tumors. This kind of lymph node should be removed as defined in the guideline. Again, the D3 gastrectomy and splenectomy did not improve outcomes.

Transcript Edited for Clarity