Where we are with gastric and esophageal cancers

June 11, 2021

Gastric and esophageal cancers are relatively rare in the U.S., where most patients present with advanced (unresectable, metastatic or both) disease. A key reason for late diagnoses is that symptoms of these cancers are challenging to pinpoint — such as nausea, bloating, dysphagia, indigestion or heartburn — which patients may consider common minor annoyances over-the-counter or other home remedies can address.

In this Q&A, a medical oncologist at Mayo Clinic's campus in Phoenix/Scottsdale, Arizona, Mohamad (Bassam) B. Sonbol, M.D., offers information on the current status of diagnosis, screening and treatment for gastric and esophageal cancers.

What is new in diagnostics for gastric and esophageal cancers?

Endoscopy is still the gold standard. Gastroenterologists with advanced training use upper endoscopy or advanced endoscopy, endoscopic ultrasound (EUS). EUS allows for not only more precision diagnosis and staging but also treatment: If physicians find localized and superficial neoplasms, they can go in with the scope and remove them.

If we detect any esophageal or gastric cancer, we move to a CT scan for further systemic staging. If this scan is negative for metastases, we do a PET/CT scan, as a PET can pick up 10% to 15% of occult metastases that CT sometimes misses. If the above is negative, diagnostic laparoscopy, especially in gastric cancer, is needed to assess any peritoneal disease.

What are the screening protocols for these cancers?

Unlike in Asia, where they have a different lifestyle and gastric and esophageal cancers are more common, screening for gastric and esophageal cancers is not recommended in the general population. Indeed, for patients who have higher risk factors, such as those with Barrett's esophagus, screening protocols are in place.

Are there any recent fundamental changes in treatment of these cancers?

Yes. Many therapeutic agents are available now, and treatments are more individualized to the patient.

Is surgery an option for patients with gastric or esophageal cancers?

Yes. Surgery is an option for patients who do not have metastatic disease and have resectable cancers. The decision regarding treatment and whether surgery is an option or not along with the timing of surgery is based on multidisciplinary discussion in a tumor board. For example, here at Mayo Clinic, medical professionals with expertise in upper gastrointestinal tumors, including surgery, medical oncology, radiation oncology, radiology, nuclear medicine and pathology, discuss any new patient with gastric or esophageal cancer at our tumor board.

Currently, surgery is the only curative option for patients with localized or locally advanced esophageal and gastric cancers. All the other treatments, including systemic therapy and radiation, are there to maximize the chance of cure and decrease risk of recurrence. Therefore, we definitely encourage surgery if the patient is eligible because that's the only curative therapy.

Do you find patients refuse surgery?

Yes. Esophagectomy, or removal of part or the entire stomach, affects swallowing, the type of meal a patient can eat and desired frequency of eating. If these patients eat a high carb load, they can experience flushing and sweating. It's a different lifestyle that some patients don't want. However, with time, some patients have completely adapted. At the end of the day, treatment is individualized to patients' needs and beliefs, and we do our best to help patients make an informed decision.

Would you talk more about what types of surgery and radiation therapy are offered?

It makes a big difference not only what type of surgery but also who does it. Studies such as the 2008 article by Wouters and colleagues in Annals of Surgical Oncology show surgery at a higher volume center will get better outcomes. Our surgeons here offer robotic and minimally invasive surgeries that have been shown to be associated with shorter recovery and less morbidity.

In addition to surgery, radiation is key. The techniques used and the process of radiation planning are very important in defining outcomes. Proton beam therapy is more focused with less additional risk of exposing surrounding structures. This is an important concept when talking about esophageal cancers, which are surrounded by the heart along with other large blood vessels.

Are there any new therapeutic options for gastric and esophageal cancer?

The last year, and more specifically the last few months, have been very exciting for our patients with upper gastrointestinal malignancies, with multiple new agents and regimens changing and improving the standard of care in metastatic gastric and esophageal cancers. This was mainly seen by the recent approvals of two immunotherapeutic agents in the front-line setting. For example, in patients with metastatic esophageal squamous cell carcinoma, the checkpoint inhibitor pembrolizumab was approved in combination with chemotherapy. Similarly, the U.S. FDA approved the combination of chemotherapy with another checkpoint inhibitor, nivolumab, in metastatic gastric adenocarcinoma. The HER2 overexpressed tumors also have seen a new approval with fam-trastuzumab deruxtecan-nxki now being available as an option for patients with HER2-positive metastatic gastric cancer.

Would you talk more about immunotherapy?

Here again, we have some immunotherapeutics that are standard care and others now in studies. There are some advantages with immunotherapy. Instead of killing cells all over the body with chemotherapy, immunotherapy wakes up the immune system to fight the cancer. In general, chemotherapy works for a while, then stops. On the other hand, when immunotherapy works, it is usually for a longer time.

The decision on which regimen to choose depends on different biomarkers. We use next-generation sequencing. We look at different targets on the cancer cells. Three patients with metastatic esophageal or gastric cancers can come in clinic today and receive three different regimens, as treatments are tailored based on multiple biomarkers found in the cancer, including HER2, MSI and PDL1, as follows:

  • We screen for MSI, as patients with MSI-high status are treated with immunotherapy, not chemotherapy.
  • We also look at HER2, which is found in about 15% to 20% of patients. Patients with HER2 overexpression get chemotherapy plus a targeted therapy with trastuzumab. Just recently, in May 2021, the Food and Drug Administration approved adding pembrolizumab, an immunotherapy, to trastuzumab and chemotherapy in patients with HER2 overexpressed gastric or gastroesophageal junction cancers, based on a study showing higher response rates in patients getting the combination.
  • We also check for PDL1, a protein we examine to answer whether the patient needs chemotherapy alone or chemotherapy plus immunotherapy.

Mayo Clinic checks its gastric and esophageal patients for all these biomarkers and screens patients for clinical trial eligibility.

Are there any therapies patients frequently talk about with you?

Patients often ask if they are eligible for immunotherapy along with other targeted therapies.

What treatment side effects do you want to see decrease for gastric and esophageal cancer patients?

Neuropathy. This side effect is common with paclitaxel and oxaliplatin, which oncologists often prescribe for patients with gastric or esophageal cancer.

What clinical trials does Mayo Clinic have available for gastric and esophageal cancers? Is there one you are particularly excited about?

We have trials and studies going for each line of therapy, which you can find on the Mayo clinical trials site. I'm really excited about our trial of a trifluridine and tipiracil combination with ramucirumab, which is now open for enrollment. We are trying to resolve the neuropathy issue by providing an alternative, effective treatment that doesn't cause neuropathy for patients requiring second line therapy. I am excited about this, as there are reports from Asia in The Lancet Gastroenterology & Hepatology in March 2021 showing higher activity of the combination (trifluridine and tipiricil plus ramucirumab) in patients who had prior immunotherapy exposure, which we expect that most of our patients will be exposed to in the first line setting.

Can current therapies cure any gastric or esophageal cancers?

Cure is possible and the goal for patients with localized and locally advanced disease. For highly selected patients with metastatic disease, like those whose cancers test as MSI-high, prolonged remission is possible.

How do you work with referred patients?

In general, we are always happy to assume care of new patients. For patients coming for second opinions and those who are established with an oncologist, we work with the patients and their referring physicians. We discuss treatment options including standard of care and clinical trial options.

If patients come in and we're not recommending something different from what they can get locally, we usually send them back to their primary oncologist with future follow-ups as needed.

For more information

Wouters MW, et al. High-volume versus low-volume for esophageal resections for cancer: The essential role of case-mix adjustments based on clinical data. Annals of Surgical Oncology. 2008;15:80.

Clinical trials: Stomach cancer. Mayo Clinic.

Clinical trials: Esophageal cancer. Mayo Clinic.

Zhu M, et al. Trifluridine/tipiracil plus ramucirumab in gastric cancer. The Lancet Gastroenterology & Hepatology. 2021;6:154.