Practical Perspectives on Treatment of Advanced Gastric/GEJ Cancers - Episode 5
Minaxi Jhawer, MD: Patients with gastric cancer or GE [gastroesophageal] cancer that is type III in the Siewert classification system fall into 1 category of being treated with a perioperative approach. The standard perioperative approach started in the United Kingdom with the MAGIC trial more than a decade ago, where they compared surgery versus epirubicin/cisplatin/5-FU [fluorouracil] chemotherapy, 3 cycles before surgery and 3 cycles after surgery, and saw a significant improvement in overall survival and reduced risk of recurrence by almost 30%. That’s become the standard of care. The overall goals of perioperative chemotherapy aim at reducing and downstaging the tumor, resulting in a higher level of R0 resection and an actual assessment of the biology of the tumor.
Patients who have more advanced disease or microscopic disease, don’t do well with chemotherapy, and after 3 months have recurrence of disease should not be taken for morbid gastrectomy. So you are actually able to prevent those patients from going through a surgery because they can declare their biology in that period of time. Those are the overall goals of perioperative chemotherapy.
David Ilson, MD, PhD: For both esophageal and gastric cancer, surgery is obviously the mainstay curative treatment, and the patient needs to be managed by a skilled surgical oncologist who knows the appropriate surgery. Adding chemotherapy to surgery has a positive impact in both of these diseases. The distinction is the role of radiation therapy. Radiation therapy is typically given to enhance the ability to operate, get a curative negative margin resection, and reduce local recurrence. Radiation therapy plays more of a role in tumors of the esophagus and GE junction, where it’s critical to get that surgical margin and reduce the risk of local recurrence. It’s a very different anatomy from what we see in the stomach. The stomach is lined with peritoneum, so there’s more room to get a negative margin. Typically, for gastric cancer management, there would be perioperative chemotherapy and a very selective application of radiation because randomized trials looking at the addition of radiation to perioperative chemotherapy show no survival benefit.
Trials from Asia show that in surgery followed by adjuvant chemotherapy, adding radiation does not impart a survival benefit. The American trial where patients got surgery, postoperative chemotherapy, and radiation only reduced local recurrence. The American trial had very poor-quality surgery. So the argument that many of us make is that in gastric cancer, if the quality of the surgery is not good—if enough lymph nodes aren’t retrieved—then you need to think about radiation to reduce the risk of local recurrence. When you perform what’s called a D2 resection and get negative margins, contemporary randomized trials do not show a survival benefit for the addition of radiation to either perioperative or postoperative chemotherapy in gastric cancer.
Now, in esophagus and GE junction cancer, there are large contemporary randomized trials: Most tellingly from Britain, 2 trials collectively treated 1900 patients. If you look at the surgical outcome with chemotherapy alone given preoperatively, curative resection rates were in the 60% range, which is unacceptable. In one study, where they treated both esophagus GE junction and gastric cancers, patients with gastric cancer who got preoperative chemotherapy had a curative resection rate of 87%. For patients with esophagus or Siewert I disease, it was 60%. Clearly, location of the tumor anatomy dictates whether or not you need to give radiation. In the United States, for esophagus and GE junction cancer, NCCN [National Comprehensive Cancer Network] guidelines endorse preoperative chemoradiation. For distal gastric cancers, we support perioperative chemotherapy with a less clear role of radiation.
Transcript Edited for Clarity