Treatment of Stages II & III of Gastric Cancer
Optimal treatment of patients with stage II - III gastric cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, surgeons, gastroenterologists and nutritionists.
Multi-modality treatment with surgery, chemotherapy and/or radiation is the primary treatment for Stage II - III gastric cancer. In general, patients with cancer that has spread to the lymph nodes have a worse outcome than patients whose cancer has not spread to the lymph nodes.
Systemic therapy and/or radiation therapy without surgery is usually reserved for patients who are not able or do not wish to undergo major surgery.
Stage II gastric cancer involves deeper layers of the stomach and/or nearby lymph nodes.
Stage III gastric cancer has spread to structures adjacent to the stomach and/or to regional lymph nodes. Stage III gastric cancer can be further divided into stage IIIA and stage IIB.
- Stage IIIA gastric cancer invades the muscle of the wall of the stomach and 7 or more lymph nodes, the next-to-the-last layer of the stomach and 3-6 lymph nodes, or the outermost layer of the stomach (the serosa) and 1-2 lymph nodes.
- Stage IIIB gastric cancer invades the next-to-the-last layer of the stomach and 7 or more lymph nodes, the outermost layer of the stomach and 3-6 lymph nodes, or adjacent structures and few (1-2) or no lymph nodes.
Surgery as Primary Treatment
Depending a patient’s circumstances, surgery may be performed with the goal of curing gastric cancer or to relieve symptoms caused by the cancer. Surgery may involve removal of all or part of the stomach, and typically includes removal of several lymph nodes as well.
Surgery is often combined with systemic therapy.3,4 Some patients receive systemic therapy both before and after surgery. For patients who don’t receive systemic therapy prior to surgery, treatment may be given in combination with radiation therapy after surgery, however clinical trials suggest that combination chemo-immunothearpy administered both before and after surgery may produce the best outcomes.
In some cases, the patient may be too ill to undergo surgery or the cancer may be too extensive to allow surgery, and the patient will be offered non-surgical approaches to treatment.
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Neoadjuvant Therapy (Treatment before Surgery)
Some patients may receive treatment with systemic therapy (with prior to surgery. This treatment can help to reduce the extent of cancer, making it easier to remove the cancer during surgery and may prolong survival.
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.
- Analyses of the MATTERHORN clinical trial continues to show the benefit of adding perioperative Imfinzi (durvalumab) checkpoint inhibitor immunotherapy to standard chemotherapy4 in patients with locally advanced, resectable gastric or gastroesophageal junction cancer. The MATTERHORN clinical trial compared perioperative Imfinzi plus FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) chemotherapy to treatment with chemotherapy alone in 948 patients with resectable gastric and gastroesophageal junction cancer. The addition of Imfinzi significantly improved the pathologic complete response rate by an absolute difference of 12%: rates were 7% with FLOT and 19% with Imfinzi plus FLOT.4
Adjuvant Therapy (Treatment after Surgery)
The goal of additional treatment after surgery is to reduce the risk of cancer recurrence by eliminating any areas of cancer that may remain in the body. Adjuvant (post-surgery) therapy for Stage III gastric cancer typically involves chemotherapy alone or in combination with radiation therapy. The use of systemic adjuvant therapy appears to improve overall survival modestly.(1)
Precision Cancer Medicines interfere with specific biological pathways involved in cancer growth or survival. A type of targeted therapy that improves outcomes for selected patients with advanced gastric cancer is Herceptin® (trastuzumab). Herceptin targets a protein known as HER2 that can stimulate cancer growth. Roughly 20% of patients with gastric cancer have cancer that over expresses (makes too much of) this protein; these cancers are referred to as HER2-positive. For patients with HER2-positive, metastatic gastric cancer, treatment with Herceptin can improve overall survival. Based on these results, studies are also evaluating the role of Herceptin and other targeted therapies for earlier-stage gastric cancer.2
Chemotherapy and Radiation Therapy as Primary Treatment
If the cancer cannot be surgically removed or the patient is medically unable to undergo surgery, treatment of Stage III gastric cancer may involve a combination of chemotherapy and radiation therapy. It appears that the combination of chemotherapy and radiation therapy has substantial activity for the local control of advanced gastric cancer.
References:
- Paoletti X, Oba K, Burzykowski T, et al. Benefit of Adjuvant Chemotherapy for Resectable Gastric Cancer: A meta-analysis. JAMA. 2010;303(17):1729-1737.
- 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 LBA246
- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32557-1/abstract
