Multiple Subgroups Needed to Properly Treat Patients With GEJ Cancers

Richard J. Bold, MD

Categorizing subgroups of patients with gastroesophageal junction (GEJ) cancers, particularly proximal GEJ cancers, is key in the proper management of patients, explains Richard J. Bold, MD, professor, chief of Surgical Oncology at the UC Davis Comprehensive Cancer Center.

“We had traditionally rolled all of the gastroesophageal junction cancers into one group, and the treatment was left up to sometimes personal expertise, sometimes personal experience with regimens, or sometimes just regional preferences,” says Bold. “The development, and more, the adaptation of the Siewert classification systems that subdivide GEJ cancers, really in the field of adjuvant therapy, has really made a difference. Because the surgeon is ultimately the one that is going to end up with these patients on our hands, this matters to us.”

OncLive: Why is it important for GEJ cancers to be properly classified?

In an interview with OncLive, Bold discusses the reasoning to break GEJ cancers into multiple subgroups and why it is important for treatment and surgical decisions. He also sheds light on the challenges that come with treating patients with gastric cancer, due to the low incidence of the disease.Bold: For those cancers that are considered more the proximal gastroesophageal junction cancers, we group them more into esophageal cancer, even though there may be some gastric component, and we will often treat those preoperatively with chemotherapy and radiation. If we move to Siewert-I, maybe even the same extent of disease, but more on the gastric side than the esophageal, those patents were getting treated with chemotherapy, omitting the radiation therapy. That will ultimately link into our surgical therapy, and this is where that preoperative and pretreatment multidisciplinary planning is critical.

What prompted this subdivision?

We need to determine if we consider a patient more esophageal, where the operation is going to be an esophagectomy for definitive surgical therapy, or if it is more of a Siewert-III, where we think we can just do a total gastrectomy for their surgical therapy. That is really important because if those 2 treatment plans aren’t aligned at the beginning, we often end up in some kind of ambiguity as to what the true extent of the disease was, and what the right therapy was.For cancers that have more extent of disease in the stomach, the biology of disease behaved a little bit more like gastric cancer. Their nodal spread was usually along the stomach and an intra-abdominal metastasis, whereas those who were more esophageal, their nodal spread was into the mediastinum with a different pattern of metastasis. Even though it is really the same organ—gastroesophageal junction—the biology of disease dictating where the dominant fraction of the disease is, is important in terms of us beginning to separate those out for both treatment surgically, as well as treatment with preoperative therapy.

Does this approach require more of a multidisciplinary treatment plan?

The other thing that has really compounded this in my mind, is that the esophageal cancer that we were seeing in the distal esophagus really was not the same esophageal cancer that people were seeing 20 years ago related to smoking. There is a lot more adenocarcinoma related to reflux. That kind of predisposition was not really the same as the gastric cancer that we saw that was extending to the esophagus. The precipitating biology seemed to be different in terms of these 2 entities and so did the biologic behavior in terms of disease risk.Yes, absolutely. Those things are really critical in terms of a team-based pre-treatment; it’s not just pre-operative planning or pre-chemotherapy. All 3 people—the radiation oncologist, if he or she is needed, the medical oncologist, and the surgical oncologist—really need to decide upfront and define what is the cancer type, and therefore, that will really dictate what the appropriate therapy is.

What are the biggest challenges in the treatment of gastric cancer?

What are the biggest barriers to making these quality-of-life improvements?

What do you see on the horizon in gastric cancer?

If all parties are not participating in that discussion, it leads to some confusion, because each party might feel that something else might be done or have planned for something else to be done. That sort of pre-treatment disease staging will dictate the disease strategy, and it really does have to be uniform.Quality of life for the patients is a troubling point for a lot of us surgically. These operations do have a significant impact on a patient’s quality of life, which is really lifelong. We’ve been looking at different ways to alter the operation and minimize those, and I don’t think even the laparoscopic or robotic techniques have addressed those long-term consequences. There has been some penetration of technologic advances in gastric cancer, more so for the distal, but we are still not to the point of widespread utilization. We are still often troubled with the long-term consequences in quality of life.I think some of it is experience. Surgical treatment of gastric cancer is not nearly as common in terms of its incidence to other gastrointestinal malignancies. Unless you are in a large center of excellence, the volume is really hard to justify the resource expenses for these new technologies and also the expertise development that goes along with that. If we are seeing one, or two gastric cancers a year that we are going to work on, it’s really hard to develop that technologic expertise and implement it safely. That is coupled with some technology barriers. It is a lot easier for technology companies to develop laparoscopic or minimally invasive techniques, instruments, or apparatuses that will impact colon cancer because colon cancer is so much more common.The concept of personalized or targeted therapy in all cancer is really what is exciting. I think when we first saw that impact of differentiating HER2-positve versus negative gastric cancer, opening up to therapy with trastuzumab, that was out first big glimmer that we were going to get to some targeted therapy. With the lower incidence of gastric cancer, it is sometimes harder to collect patient information and do the genomic analysis so we can begin to do that molecular subtyping of cancer so we can target it. That has been a little more difficult to get a large group of patients and data together. Certainly, the national effort through the genomic studies to collect this data is an important step in that. We are going to have to continue to investigate the genomics and examine and identify the targets, and then move into clinical trials.