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, medical gastroenterologists, radiation oncologists, medical oncologists and nutritionists.
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 after surgery. 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. Connection to the duodenum is considered to be a more feasible method, but is often not performed for fear a cancer recurrence will cause an obstruction. Cure rates for gastric cancer are related to the extent of cancer at the time of diagnosis.
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.
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. In one clinical study, 618 patients with cancer of the lower part of the stomach were randomly assigned to treatment with subtotal gastrectomy or total gastrectomy. Both surgical treatments included removal of regional lymph nodes. The death rate following subtotal gastrectomy was 1%, compared to 2% following total gastrectomy. Five years following surgery, 65% of patients undergoing subtotal gastrectomy were alive, compared to 62% of patients undergoing total gastrectomy. This study showed that treatment with total and subtotal gastrectomy were equivalent in terms of survival, but patients in this trial who were treated with subtotal gastrectomy maintained better digestive function.
The major complications of surgery include pneumonia and leaking at the site where the esophagus is connected to the remaining stomach or small intestine. The mortality rate following surgery is 0-5%, with the chance of dying from complications of surgery being slightly greater in patients treated with total gastrectomy. Surgery performed by an inexperienced surgeon tends to result in more complications. Patients should inquire as to the specific mortality and complication rates at the center where the surgery will be performed.
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. Although it is not commonly performed in western countries, the use of laparoscopic curative resection for gastric cancer is growing, especially in Japan. Laparoscopic resection of early gastric cancer has been shown to be safe and effective in many retrospective studies, although no randomized studies have been performed to directly compare laparoscopic surgery to open resection. Despite being more controversial, laparoscopic curative resection of advanced gastric cancer has been performed at multiple institutions with encouraging early results. The primary advantage of laparoscopic surgery is more rapid recovery after surgery.
Lymphocytes and the lymph system are part of the body’s immune system that protect 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.
In the United States and Europe, the results from two retrospective reviews have encouraged some physicians to advocate extended lymph node removal. However, in one prospective randomized clinical trial, extensive lymph node removal resulted in more deaths and complications than less extensive lymph node dissection. Furthermore, the 5-year survival rates were similar for both groups (45% for extensive node removal and 47% for less extensive node removal). The average number of lymph nodes removed in the less extensive group was 15, compared to 30 lymph nodes for the more extensive group. In some cases, the spleen and half the pancreas are removed to gain access to lymph nodes, which has been associated with increased complications and no proven benefit on survival. Thus, extensive lymph node removal is currently not routinely recommended for patients in the United States. It is recommended that at least 15 lymph nodes be removed and some doctors, especially in Japan, advocate more extended removal of lymph nodes.
It is important to understand that some patients with gastric cancer already have small amounts of cancer that have spread into the lymph nodes and cannot be reliably detected with any of the currently available tests. Undetectable areas of cancer are referred to as micrometastases. The presence of micrometastases causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient’s duration of survival and potential for cure. The delivery of cancer treatment following local treatment with surgery is referred to as adjuvant therapy and may include chemotherapy, radiation therapy and/or biologic therapy.
Several clinical trials have suggested that chemotherapy administered after surgery may prevent some cancer recurrences; however results from other clinical trials have not shown this effect. In order to determine the effectiveness of chemotherapy after surgery in preventing recurrences, doctors in Canada analyzed results from 13 major clinical trials that compared adjuvant chemotherapy treatment to no additional treatment following surgery for gastric cancer. They found a modest benefit for patients treated with adjuvant chemotherapy. The results indicated that 65% of patients treated with surgery alone experienced a recurrence and died, compared to approximately 61% of patients receiving adjuvant chemotherapy. The greatest benefit appeared to be in patients treated with more modern chemotherapy drugs. Over the past few years, several new chemotherapy drugs have been developed that appear to have more anti-cancer activity and are being evaluated in clinical trials.
Results from a large multi-institutional clinical study also indicate that adjuvant therapy significantly improves survival for patients with gastric cancer and should become the standard of care for this disease. The trial involved over 500 patients with gastric cancer who received surgery alone or surgery plus a combination of chemotherapy and radiation. All patients in the study underwent surgery to remove their cancer and had no evidence of cancer remaining following the surgical procedure. Half of the patients then received adjuvant combination chemotherapy consisting of 5-FU and leucovorin plus radiation. Three years following therapy, 50% of patients treated with surgery followed by adjuvant chemotherapy and radiation survived, compared with only 41% of patients treated with surgery alone. Three years following treatment, 48% of patients treated with adjuvant therapy survived without a cancer recurrence, compared to only 31% treated with surgery alone. The average duration of survival following surgery was 27 months, compared with 36 months for patients receiving surgery and adjuvant therapy.
Another clinical trial evaluated adjuvant chemotherapy without radiation in gastric cancer patients. All patients in this trial had cancer that had spread to nearby lymph nodes and were eligible for curative surgery. Half of the patients received combination chemotherapy consisting of epidoxorubicin, leucovorin and 5-fluorouracil for 7 months following surgery while the other half of patients received no adjuvant therapy (control group). Five years following therapy, 30% of the patients receiving adjuvant chemotherapy were still alive, compared with only 13% from the control group. The average survival time following treatment was 31 months for patients receiving adjuvant chemotherapy and only 18 months for the control group.
Results from both of these clinical trials are consistent with previous studies indicating that adjuvant therapy improves outcomes for patients with gastric cancer. The researchers in these studies have concluded that surgery following adjuvant therapy for stage I to IV gastric cancer reduces cancer recurrences and improves overall survival compared with surgery alone. Adjuvant therapy is considered the standard treatment for patients with gastric cancer for whom all detectable cancer can first be removed by surgery.
The progress that has been made in the treatment of gastric cancer has resulted from improved patient participation in clinical studies. Future progress in the treatment of gastric cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of gastric cancer.
Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Supportive Care.
Extensive Lymph Nodes Resection: Controversy remains concerning how many lymph nodes should be removed during surgery. Clinical trials comparing more extensive to less extensive removal of lymph nodes are ongoing.
Adjuvant Therapy: The administration of additional treatment after surgery for the purpose of decreasing the risk of cancer recurrence is referred to as adjuvant therapy. Clinical trials have demonstrated an improvement in survival when adjuvant therapy is used to treat all stages of gastric cancer except stage IA. Clinical trials are ongoing to determine the optimal adjuvant therapy.
Neoadjuvant Therapy: The practice of administering chemotherapy before surgery is referred to as neoadjuvant therapy. In theory, neoadjuvant chemotherapy can decrease the size of the cancer, thereby making it easier to remove with surgery. There is currently no evidence that chemotherapy, radiation therapy or both given before surgery improves survival for patients receiving surgery for gastric cancer. With the development of new chemotherapy regimens, there will be many new clinical trials designed to evaluate neoadjuvant therapy in patients with gastric cancer undergoing gastrectomy.