Practical Perspectives on Treatment of Advanced Gastric/GEJ Cancers - Episode 7
David Ilson, MD, PhD: We identify high-risk patients for neoadjuvant treatment with staging techniques, endoscopic ultrasound being the most important, and making sure we have CT [computed tomography] and PET [positron emission tomography] scans to rule out metastatic disease. Occasionally, we do understage patients. We think we have an early T1- or T2-stage tumor in gastric cancer, but let’s say the pathology comes back T3N1. That is a high-risk patient. Then we extrapolate from Asian data, where there is clear evidence in gastric cancer from thousands of patients treated with D2 gastrectomy that 6 months to a year of adjuvant chemotherapy also improves survival. So in a patient who has undergone an up-front surgery, as long as they’ve had a good resection—D2 resection with negative margins or if they’re node-positive, we would occasionally treat T3N0—we would consider adjuvant chemotherapy, which translates into very similar survival benefits that we see with perioperative chemotherapy.
If you look across the board, the risk reduction is about a 25% to 30% reduction in the risk of recurrence, which typically translates into about a 10% to 15% survival benefit at 5 years. If a patient has had up-front surgery, we would consider adjuvant chemotherapy. The exception would be the American trial in gastric cancer, where the quality of surgery was poor with low lymph node retrieval. For that patient, if they have positive nodes and the surgeon retrieved fewer than 10 to 15 nodes, I might consider the addition of postoperative radiation.
Now, for esophagus and GE [gastroesophageal] junction cancers, it’s very hard to give postoperative radiation. The field is huge, and it’s poorly tolerated. So if we have an understated esophagus GE junction tumor that’s stage T3 or node-positive, if the surgery was appropriate and margins were negative, we might also consider adjuvant chemotherapy. But that’s a rare patient. We advocate for neoadjuvant treatment in these patients if possible, as it’s better tolerated and we get survival benefits.
Minaxi Jhawer, MD: With the advent of a perioperative chemotherapy being the standard of care, most of the patients who have disease beyond stage T3, all nodal positivity, should definitely be getting perioperative chemotherapy up front.
We occasionally come across patients who have had surgery up front. What do we do for those patients? The standard approach is based on the 0116 study, which was a United States Intergroup trial from years ago that has validated adjuvant chemoradiation as the standard of care in these patients. The only difference is that we don’t use the bolus 5-FU [fluorouracil], as it was used concurrently with radiation in the original arm. I tend to change it to an infusional 5-FU arm with the radiation and then give 5-FU cycles before the chemoradiotherapy is started and then after the chemoradiotherapy is completed.
What’s interesting is that the data really showed that patients who had inadequate surgery, less than a D2 dissection, were the ones who benefited with the radiation. That was the reason that the radiation worked and helped them in the adjuvant arm. But with our patients’ getting better surgery, better D2 dissections, the question is what the role of radiation is in these patients. I tend to resort to perioperative chemotherapy as a standard, in which case, because we have a multidisciplinary clinic, we discuss it with the patients up front. They don’t generally go to surgery if they have stage T3 or higher disease, and so we give them chemotherapy before and after. If, for some reason, they’ve had a D1 or lower level of dissection, those patients we tend to address with adjuvant radiation.
Transcript Edited for Clarity