State of Stomach Cancer Research and Care: Q+A with Drs. Ryan Moy and Sam Yoon
Stomach cancer, or gastric cancer, is considered an uncommon cancer type in the U.S. An estimated 26,000 new cases of stomach cancer are diagnosed each year, a stark contrast to high rates in countries like China, Korea, and Japan, making it one of the leading causes of cancer-related deaths in the world. Korea and Japan currently have established national screening guidelines to catch the disease early.
With stomach cancer mortality and incidence rates gradually decreasing, the U.S. currently does not have a national screening program for stomach cancer. Still, the main challenges of stomach cancer, particularly in the U.S., are disease prevention and early diagnosis. Stomach cancer is curable but a delay in diagnosis could lead to advanced local disease and metastasis.
Physician-scientists Ryan Moy, MD, PhD, and Sam Yoon, MD, members of the Herbert Irving Comprehensive Cancer Center (HICCC) who were recruited to Columbia University Irving Medical Center (CUIMC) in the summer, specialize in stomach cancer, and share insights about the disease and the state of the field today in terms of advancement in research and treatment.
Dr. Moy, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons (VP&S) focuses on esophageal and gastric cancers and understanding the biology by which these cancers spread to distant organs as well as developing new treatment strategies for these cancers. Dr. Yoon, chief of Columbia’s new Division of Surgical Oncology and professor of surgery in the Department of Surgery, is a leading expert in the treatment of patients gastric, gastroesophageal cancers, and gastrointestinal stromal tumors. Dr. Yoon’s main research interests are in cancer stem cells and targeted biological agents in combination with chemotherapy and radiation therapy.
What are common risk factors of stomach cancer?
RM: Stomach cancer is a rare cancer in the United States but worldwide, it’s actually one of the most common cancers with about a million people diagnosed each year. It's the fifth most common cancer in the world. One of the most common risk factors is infection with Helicobacter pylori , or H. pylori, along with dietary factors like a high-salt diet or a diet high in smoked foods, smoking, having a family history of stomach cancer, and obesity.
SY: People who have H. pylori infection often get it in childhood or at an early age. The bacteria colonizes your stomach, causing chronic inflammation that over decades leads to cancer. H. pylori infection rates correlate very well with gastric cancer incidence rates throughout various countries. Japan, Korea, and China all have very high H. pylori infection rates, which is why they have such high gastric cancer rates. Similarly, increased levels of H. pylori infection are found in Russia, the former Soviet countries, Mediterranean countries, and parts of Central and South America.
Some of those countries have established stomach cancer screening programs to detect the disease early. Why don’t we screen for stomach cancer in the U.S.? What is involved in a screening?
RM: We don't screen for stomach cancer in the U.S. like we do for colon cancer with regular colonoscopies because it isn’t that common in the United States. So unfortunately, many people who develop stomach cancer aren’t diagnosed until their cancer is more advanced, either locally advanced disease involving deeper layers of the stomach or the surrounding lymph nodes, or stage four metastatic disease where the cancer has spread to other organs.
Oftentimes these cancers grow quickly where we might not necessarily find them on a regular upper endoscopy [how we screen for stomach cancer]. Sometimes patients will develop symptoms related to stomach cancer, such as abdominal pain, weight loss, difficulty eating, and at that time, that may prompt them to see a gastroenterologist and get an endoscopy and only then, after they already have significant symptoms, we will find the cancer.
Is stomach cancer curable? How is it treated?
RM: Stomach cancer is curable when the stomach cancer is localized to the stomach or surrounding lymph nodes. The standard treatment for patients with locally advanced gastric cancer is to give perioperative chemotherapy before and after surgery. Stomach cancers that are more advanced (i.e. metastatic) are treatable with systemic therapies that go throughout the whole body, but not generally curable. For advanced stomach cancer, it is important to get biomarker testing (including PD-L1, HER2, and MSI status) to determine the best treatment regimens and personalize therapy to the patient’s individual tumor.
What are some recent surgical advances for stomach cancer?
SY: A significant improvement in stomach cancer treatments is the improved staging of patients. We treat patients differently based on their clinical stage or how advanced their disease is. One of the big advances is endoscopic ultrasound, which can evaluate the depth of the tumor. Ten years ago, while it was probably available, physicians weren’t very good at it; the technology is very operator-dependent. There are a select number of gastroenterologists who have become very skilled at endoscopic ultrasound. For very superficial tumors, early-stage tumors, some of these gastroenterologists can perform a technique called endoscopic submucosal dissection, where they can actually remove the tumor curatively, just endoscopically. We have Amrita Sethi, MD, here who is an expert in this technique. And if the tumor is deeper, an expert like Dr. Sethi can tell us how deep it is.
If the tumor is relatively early but not amenable to endoscopic resection, we generally operate up front. For more locally advanced tumors, we give chemotherapy first and then operate.
There’s also been a move toward laparoscopic and robotic surgery. There have been a lot of studies out of Korea, Japan, and China showing that laparoscopic surgery can reduce blood loss, post-operative pain, and hospital stay and have equivalent oncologic outcomes. The main problem with that is that in countries where gastric cancer is uncommon, like in the U.S., surgeons are less experienced, both in gastric cancer surgery and in laparoscopic surgery, as opposed to surgeons in countries like Japan, Korea, and China where the incidence of gastric cancers are much, much higher. It can be challenging for surgeons who aren’t doing a significant volume of these surgeries. There is a steep learning curve, especially for the lymph node dissection. Some inexperienced surgeons will do an inadequate lymph node dissection, and may leave cancer-containing lymph nodes behind.
How has treatment changed for stomach cancer?
RM: Surgery is still the primary component of treatment but we know that there's a high risk for cancer to recur, and that's why we often use multi-modality therapies. For instance, we give patients chemotherapy before and after surgery to target micro-metastatic cancer and reduce the risk of cancer recurrence.
There's a lot of interesting research now trying to understand how we can approve on our current standards of therapy. One thing that I'm excited about is the use of immunotherapy, which works differently than chemotherapy. Immunotherapy drugs work by enabling the body's own T cells to recognize and kill cancer cells. This is quite exciting because, as we know, the body's immune system builds memory against things like infection, that this could potentially lead to more durable long lasting responses against cancer and can decrease the chance that the cancer will spread, or allow patients to live longer without having their cancer cause any future problems. We know that the combination of chemotherapy and immunotherapy in the metastatic setting [when disease spreads] improves outcomes for patients, and there are many ongoing clinical trials now seeing whether adding immunotherapy to perioperative chemotherapy can similarly improve outcomes and increase the chance of a cure.
What does the future hold for stomach cancer research?
SY: Similar to many other cancers, we're learning that it's not just one monolithic entity, one big entity; there are classes of gastric cancer that may behave differently and respond differently to treatments. I think the biggest advance within the past five or 10 years in that regard was a study by Adam Bass, MD, (recruited to Columbia last year) on the molecular classification of gastric cancer into four categories: CIN, short for chromosomal instability; GS which stands for genomically stable; MSI, which is microsatellite instability; lastly, Epstein-Barr Virus (EBV)- associated gastric cancer. Those four gastric cancer types have different genetics, different prognosis, and also different responses to chemotherapy and immunotherapy. As we're getting more and more into this era of personalized medicine, where we're further categorizing cases, not just into four types, but maybe and ultimately, we are getting to a place where we can categorize the cancer into just your type.