Medically reviewed by C.H. Weaver M.D. Medical Editor updated 6/2019
Surgery is part of the standard treatment for the majority of patients with gastric cancer. However, since gastric cancer is not exclusively treated by surgery, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving surgeons, gastroenterologists, radiation oncologists, medical oncologists and nutritionists. Multi-modality therapy may consist of chemotherapy, radiation, and precision cancer medicines. Given the poor outcomes with advanced disease patients should also consider participation in clinical trials evaluating newer precision cancer medicines.
Systemic therapy is any treatment directed at destroying cancer cells throughout the body, and may include chemotherapy, precision cancer medicines or immunotherapy. Treatment of patients with stage II - III or locally advanced gastric cancer often consists of systemic treatment combined with surgery or radiation and systemic treatment is routinely used in stage IV or recurrent cancer. All patients should undergo genomic biomarker testing in order to determine if they can benefit from treatment with precision cancer medicines.
Surgery for Gastric Cancer
Individuals with gastric cancer are frequently treated with surgical removal of the stomach (called a gastrectomy), to remove the cancer and prevent recurrence (or return) of the cancer. Lymph nodes (parts of the body’s lymph system) around the stomach are also removed and examined to determine whether or not the cancer has spread to these areas. Depending on the stage (extent of disease) of the cancer, the majority of patients will also be treated with chemotherapy drugs and/or radiation therapy.
A complete removal of the primary cancer and the lymphatic drainage of the cancer is the primary goal of any surgical treatment for gastric cancer. Patients with gastric cancer may have a total or partial removal of the stomach. When patients undergo a partial removal of the stomach, the remaining portion of the stomach is re-attached to the upper part of the small intestine (duodenum) or to the middle part of the small intestine (jejunum) or to the esophagus. Cure rates for gastric cancer are related to the extent of cancer at the time of diagnosis.
- Total Gastrectomy - During a total gastrectomy, the entire stomach is removed and the two remaining ends of the gastrointestinal tract are reconnected. This is the most common operation for cancer of the upper stomach. For cancers of the middle and lower stomach, an incision is made in the abdomen and the entire operation can be carried out without entering the chest. The usual operation for cancer of the upper stomach, called the cardia, is an incision that involves entering both the abdomen and the chest. An alternative approach is a single incision in the abdomen with an incision through the diaphragm (transhiatal approach). The transhiatal approach for total gastrectomy for cancer of the upper stomach is a safe alternative to the standard thoracoabdominal technique and avoids entering the chest and the associated complications.
- Subtotal Gastrectomy - Treatment of patients with cancer of the lower part of the stomach has frequently involved the complete removal of the stomach. An alternative operation is removal of only the part of the stomach involved with cancer with preservation of the upper stomach. This is called a subtotal gastrectomy. The less extensive operation is associated with better nutrition and quality of life than total gastrectomy.
- Endoscopic Surgery - Early cancers (Stage 0 and I) can often be removed through an endoscope passed through the esophagus. Another procedure, called laparoscopic surgery, is performed through an endoscope passed into the abdomen through a small incision. Studies conducted thus far suggest that laparoscopic surgery is safe and effective for selected patients; additional, larger studies are needed before firm conclusions can be drawn. The primary advantage of laparoscopic surgery is more rapid recovery after surgery.
- Extent of Surgery - Lymphocytes and the lymph system are part of the body’s immune system that protects the body from disease and infection. The lymph system consists of small bean-shaped “lymph nodes” connected by ducts, which are extensively located throughout the gastrointestinal tract. When cancer originates in the stomach, cancer cells may spread through the lymph nodes to other parts of the body. In some, but not all clinical studies, improved survival is associated with more extensive removal of the lymph nodes. This has led some surgeons to recommend removing the maximum number of lymph nodes during surgery. However, this more extensive surgery is often associated with increased complications. Thus, controversy remains regarding the appropriate extent of lymph node removal.
Systemic Adjuvant Therapy (Treatment after Surgery)
Most patients with gastric cancer already have small amounts of cancer that have spread beyond the stomach that could not be removed with surgery and cannot be detected with any of the currently available tests. These undetectable areas of cancer are referred to as micrometastases and they are responsible for cancer recurrence following treatment with surgery alone.
Additional systemic treatment aimed at these micrometastases can improve duration of survival and potential for a cure in some patients. The delivery of cancer treatment following local treatment with surgery is referred to as adjuvant therapy.
Neoadjuvant Therapy (Treatment before Surgery)
Some patients may receive treatment with systemic therapy (with or without radiation therapy) prior to surgery. This treatment can help to reduce the extent of cancer, making it easier to remove the cancer during surgery. Patients who receive systemic therapy prior to surgery often receive systemic therapy after surgery as well.
Types of Systemic Therapy
Systemic therapy may consist of chemotherapy, immunotherapy, or precision cancer medicines used individually or in combinations. Clinical trials have demonstrated an improvement in survival when systemic adjuvant therapy is used to treat all stages of gastric cancer except stage IA.
All patients with advanced gastric cancer should undergo genomic biomarker testing for HER2 and other targets in order to determine if they can benefit from treatment with a precision cancer medicine.
- Chemotherapy - Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Several different chemotherapy drugs are approved for treatment of gastric cancer.(2-4)
- 5 - Flourouracil
- Xeloda (capecitabine)
- Lonsurf (Trifluridine/tipiracil)
- Lynparza (rubraca)
- Cyramza (ramucirumab)
- Precision Cancer Medicines for Gastric Cancer - Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be used to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack gastric cancer cells with specific abnormalities, leaving normal cells largely unharmed.
- Herceptin® (trastuzumab) is a targeted therapy that interferes with specific pathways involved in the growth or spread of cancer. A protein known as HER2 (human epidermal growth factor receptor contributes to cancer growth and cancers that test positive for HER2 may be treated with a HER2-targeting drug called Herceptin® (trastuzumab). Herceptin can be used alone or in combination with chemotherapy, and can prolong patient survival with advanced, HER2-positive gastric cancer. (5)
- NTRK-fusion proteins are uncommon but if present can be targeted with Larotrectinib.(6)
- Precision Immunotherapy - Checkpoint Inhibitors are monoclonal antibodies that helps to restore the body’s immune system in fighting cancer. They create their anti-cancer effects by blocking a specific protein used by cancer cells called the programmed death-1 (PD-1), to escape an attack by the body’s immune system. When PD-1 is blocked or inhibited, cells of the immune system are able to identify cancer cells as a threat and initiate an attack to destroy the cancer.
- Keytruda (pembrolizumab**)** - The KEYNOTE 059 clinical trial compared Keytruda, Keytruda + chemotherapy and chemotherapy alone in patients with advanced gastric cancer. Keytruda as a single drug was as good as chemotherapy but the combination was no better. (7)
- Opdivo (nivulomab) was found to produce superior survival duration compared to placebo in patients with advanced gastric cancer. (8)
Radiation Therapy for Gastric Cancer
Radiation therapy may be an integral part of the treatment of gastric cancer. However, since gastric cancer is not exclusively treated with radiation therapy, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, surgeons, medical gastroenterologists, and nutritionists.
The objective of radiation therapy to the stomach is to kill cancer cells that could otherwise persist and cause the cancer to relapse. Radiation therapy uses high energy x-rays to kill cancer cells that remain in or near the stomach and surrounding lymph nodes. Radiation therapy is usually delivered to the stomach and surrounding lymph nodes from a machine outside the body, called a linear accelerator.
Radiation therapy alone is not usually recommended for primary treatment of gastric cancer because radiation administered in combination with chemotherapy appears superior when compared to treatment with radiation alone. Radiation therapy, however, is utilized as palliative therapy for patients who have inoperable gastric cancer or for patients who cannot undergo surgery or chemotherapy. Radiation therapy can also be utilized to treat patients who have a recurrence after surgery. However, in this situation patients typically also receive simultaneous chemotherapy and radiation therapy.
The role of radiation therapy is limited in patients with unresectable or stage IV metastatic cancer. The primary treatment remains combination chemotherapy. Radiation therapy alone, however, can be used to decrease the symptoms from gastric cancer in patients with more advanced disease who are medically unable to receive surgery or chemotherapy or for patients who have a recurrence after surgery. However, patients with recurrent cancer usually receive combination chemotherapy.
Delivery of Radiation Therapy for Gastric Cancer
Modern radiation therapy for gastric cancer is delivered via machines called linear accelerators that produce high energy external radiation beams that penetrate the tissues and deliver the radiation dose deep into the areas where the cancer resides. These modern machines and other state-of-the-art techniques have enabled radiation oncologists to significantly reduce side effects, while improving the ability to deliver a curative radiation dose to cancer-containing areas and minimizing the radiation dose to normal tissue. For example, with modern radiation therapy, skin burns almost never occur, unless the skin is being deliberately targeted or because of unusual patient anatomy.
After an initial consultation with a radiation oncologist, the next session is usually a planning session, which is called a simulation. The simulation session is used to determine radiation treatment fields and most of the treatment planning. Of all the visits to the radiation oncology facility, the simulation session may actually take the most time. During simulation, detailed pictures are taken of the cancer and the areas surrounding the cancer, often using computed tomography (CT) scans. Temporary marks may be made on the patient’s skin with magic markers. Body molds or other devices may be constructed to help the patient stay in one position. The radiation oncologist is aided by one or more radiation technologists and often a dosimetrist, who performs calculations necessary in the treatment planning. The simulation may last anywhere from fifteen minutes to an hour or more, depending on the complexity of what is being planned.
Once the aspects of the treatment fields are satisfactorily set, the patient may be given multiple “tattoos” which mark the treatment fields and replace the marks previously made with magic markers. These tattoos are not elaborate and consist of no more than pinpricks followed by ink, appearing like a small freckle. Tattoos enable the radiation technologists to set up the treatment fields each day with precision, while allowing the patient to wash and bathe without worrying about obscuring the treatment fields. Radiation treatment is usually given in another room separate from the simulation room. The treatment plans and treatment fields resulting from the simulation session are transferred over to the treatment room, which contains a linear accelerator focused on a patient table. The treatment plan is verified and treatment started only after the radiation oncologist and technologists have rechecked the treatment field and calculations, and are thoroughly satisfied with the “setup”.
Side Effects of Radiation Therapy
The majority of patients are able to complete radiation therapy without significant difficulty. Side effects and potential complications of radiation therapy are limited to the areas that are receiving treatment with radiation. The chance of a patient experiencing side effects, however, is highly variable. A dose that causes some discomfort in one patient may cause no side effects in other patients. If side effects occur, the patient should inform the technologists and radiation oncologist because treatment is almost always available and effective.
Radiation therapy to the abdominal/pelvic area may cause diarrhea, abdominal cramping or increased frequency of bowel movements or urination. These symptoms are usually temporary and resolve once the radiation is complete. Occasionally, abdominal cramping may be accompanied by nausea.
Blood counts can be affected by radiation therapy. In particular, the white blood cell and platelet counts may be decreased. This is dependent on how much bone marrow is in the treatment field and whether the patient has previously received or is receiving chemotherapy. These changes in cell counts are usually insignificant and resolve once the radiation is completed. However, many radiation therapy institutions make it a policy to check the blood counts at least once during the radiation treatments. It is not unusual for some patients to note changes in sleep or rest patterns during the time they are receiving radiation therapy and some patients will describe a sense of tiredness and fatigue.
Late complications following radiation treatment of gastric cancer are infrequent. Potential complications do include bowel obstruction, ulcers or second cancers caused by the radiation. The probabilities of these late complications are also affected by previous extensive abdominal or pelvic surgery, radiation therapy and/or concurrent chemotherapy.
- Huscher CG, Mingoli A, Sgarzini G et al. Laparoscopic versus open subtotal gastrectomy for distal gastric cancer: five-year results of a randomized prospective trial. Annals of Surgery. 2005;241:232-7.
- Yung-Jue Bang, MD, PhD et al. online in the Journal of Clinical Oncology.
- Shitara, K., Doi, T., Dvorkin, M., et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2018;19(11): 1437-1438.
- Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet. Published early online October 3, 2013. doi:10.1016/S0140-6736(13)61719-5
- Bang Y-J, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376:687-697.
- Abstract LBA28_PR ‘KEYNOTE-059 Update: Efficacy and Safety of Pembrolizumab Alone or in Combination With Chemotherapy in Patients With Advanced Gastric or Gastroesophageal (G/GEJ) cancer.