Advances in Upper Gastrointestinal Cancer Treatment

Upper gastrointestinal (GI) cancers include cancer of the esophagus (the tube that carries food from the mouth to the stomach), the stomach, and the small intestine. These cancers can sometimes be difficult to treat, but new tools and medicines are detecting cancer earlier and helping people live longer.

Jump to Key Takeaways.

Finding Upper GI Cancer Earlier

One of the best ways to improve cancer outcomes is to detect it early, before it can grow very large or spread into different areas of the body.

Endoscopies are imaging procedures in which a camera on a flexible tube is placed into the upper GI tract. High-definition endoscopes provide a significantly clearer view of the upper digestive tract. These scopes can find tiny changes in the lining of the esophagus or stomach that may be cancerous or precancerous cells.

Special lights and dyes can also help highlight areas in the esophagus or stomach that may be suspicious for cancer. A tool called confocal laser endomicroscopy enables healthcare providers to see cells up close while the scope is still inside the body. These can help determine the best areas for a biopsy (removal of a sample to analyze in the lab for the presence of cancer cells).

Artificial intelligence (AI) is being used in some cases to assist in reading images from scopes. Computers can now help see suspicious areas that might be missed by the human eye. Although the use of AI may still be under clinical investigation, it’s a promising development in the early detection of upper GI cancer.

Immunotherapy Advancements

One of the biggest advancements in upper GI cancer care is the use of immunotherapy. This type of medicine helps the body’s own immune system find and attack cancer cells. Some cancers grow because they can “hide” from the immune system. Immunotherapy stops the cancer from being able to hide.

In esophageal and stomach cancers, certain immunotherapy drugs are now used along with chemotherapy:

• Opdivo (nivolumab) helps people with esophageal cancer live longer when used after surgery and radiation.
• Ketruda (pembrolizumab) can help when used with chemotherapy in some patients with advanced cancer.

Researchers are also investigating whether immunotherapy can help before surgery. In some studies, people who took it before surgery had smaller tumors and better recovery.

A study presented in June 2025 showed that a combination of chemotherapy and immunotherapy with Imfinzi (durvalumab} helped reduce the risk of upper GI cancer coming back when given before and after surgery.

Targeted Therapy Advancements

Not all upper GI cancers are genetically the same. Each cancer can have its own genetic fingerprint. Some cancers have gene mutations (changes) that can be treated by a medication that targets those mutations specifically.  

For example, some stomach cancers have cells that have too much of a protein called human epidermal growth factor receptor 2 (HER2). People with HER2-positive cancer can benefit from a HER2-directed medication such as Herceptin (trastuzumab).

In addition to HER2, other targeted treatments might be helpful for some people. These medications can target the pathways of:

• Vascular endothelial growth factor (VEGF): A signaling protein that stimulates the formation of new blood vessels
• Neurotrophic tyrosine receptor kinase (NTRK): Abnormal gene fusions that can fuel the growth of some cancers
• Claudin18.2 (CLDN18.2): A molecule that helps hold epithelial cells together
• Fibroblast growth factor receptor (FGFR): A molecule active in cell growth, differentiation, survival, and migration that can contribute to progression of some cancers
• Epidermal growth factor receptor (EGFR): A protein that can drive abnormal cell growth

Improvements in Surgical Techniques

Surgery is still an important part of treating many upper GI cancers. The goal of surgery is usually to remove the tumor completely.

Surgeries now are often done using smaller incisions and using laparoscopic or robot-assisted tools. These methods usually mean less pain, shorter hospital stays, and quicker healing:

• Laparoscopic surgery is performed by making two or more small incisions and inserting a camera and tools to perform the surgery. It is minimally invasive.
• Robot-assisted surgery is performed laparoscopically, using very small surgical tools attached to robotic arms. A surgeon controls the robotic arms from a viewing screen rather than directly manipulating them.

In addition to different surgical techniques, neoadjuvant chemotherapy or immunotherapy is now being used more often. Neoadjuvant means that treatment is given before surgery to try to shrink the tumor to make surgery easier. Chemotherapy with or without immunotherapy may continue after surgery to reduce the risk of the cancer coming back.

Improvements in Screening and Surveillance

Screening means looking for cancer before it causes any symptoms, and surveillance is looking for cancer recurrence after it’s been treated. For some people who are at high risk of developing upper GI cancer, periodic endoscopies may help find cancer before it starts or spreads.

Key Takeaways

• New tools are helping healthcare providers detect upper GI cancers earlier, including high-definition scopes, specialized imaging dyes, and artificial intelligence that can identify cancer signs more accurately.
• Immunotherapy and targeted treatments are improving survival, especially when used alongside chemotherapy or before and after surgery to shrink tumors and reduce the chance of cancer coming back.
• Surgery is becoming safer and more effective, with less invasive techniques and better outcomes when combined with treatments like chemotherapy or immunotherapy before and after the operation.