Stage III Gastric Cancer
Overview
Patients with stage III gastric cancer have spread of cancer 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 either 1) invades into the muscle of the wall of the stomach with 7-15 lymph nodes involved, or 2) invades the lining of the abdomen (peritoneum) without invading local structures with 1-6 lymph nodes involved, or 3) invades the adjacent local structures without lymph node spread. Stage IIIB cancer invades the lining of the abdomen (peritoneum) with 7-15 lymph nodes involved.
A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.
The following is a general overview of the treatment of stage III gastric cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.
Optimal treatment of patients with stage 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, medical gastroenterologists and nutritionists.
Surgery as Primary Treatment
It is important for patients with gastric cancer to consider receiving treatment at a large medical center because improved survival rates have been reported at these facilities.
In general, surgery alone is not usually advised for patients with stage III gastric cancer except for palliation. In a large study that involved over 50,000 patients with all stages of gastric cancer treated between 1985 and 1996 in many different medical centers, the 5 and 10-year survival rates for patients with stage IIIA cancer were only 20% and 14%, respectively. The 5 and 10-year survival rates for patients with stage IIIB cancer were 8% and 3%, respectively. Patients with cancers of the upper stomach had a worse outcome than patients with cancers of the lower stomach. The number of lymph nodes removed for evaluation varied greatly, suggesting differences in completeness of surgery. Patients who had 15 or more lymph nodes removed had a better survival than patients who had fewer lymph nodes removed when compared stage by stage of the primary cancer. This suggests that many patients had inadequate surgery.
Patients with stage III gastric cancer should consider treatment at a medical center with a surgical team that has experience and treats a large number of patients with gastric cancer each year. To learn more about surgical treatment, go to Surgery and Gastric Cancer.
Adjuvant Therapy (Treatment after Surgery)
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 detected with any of the currently available tests. Undetectable areas of cancer are referred to as micrometastases. It is the presence of micrometastases that 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 a 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-fluorouracil 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.
Neoadjuvant Therapy (Treatment before Surgery)
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. The major problems with this approach are the higher mortality rates that occur when radiation therapy and/or chemotherapy are administered before surgery and the delay of surgery for some patients who do not respond to therapy. In most but not all studies chemotherapy, radiation therapy or both given before surgery have not improved survival following surgery in patients with stage III gastric cancer. This may be related to the ineffectiveness of the drug combinations tested, which include various combination of 5-FU, doxorubicin and methotrexate. Many current clinical trials are directed at improving outcomes of patients with stage III gastric cancer by administering newer neoadjuvant treatment regimens containing taxane chemotherapy and/or radiation therapy.
Chemotherapy as Primary Treatment
Patients with stage III gastric cancer are frequently included in clinical trials to evaluate new chemotherapy regimens without radiation therapy. The most frequently used agents are Platinol®, 5-FU, doxorubicin, Ellence®, Mutamycin® and more recently, Taxotere®, Gemzar® and paclitaxel. Single drugs rarely produce a complete response, while combinations of drugs produce complete responses in 10%-25% of patients with stage III gastric cancer. Unfortunately, the average duration of survival for these patients is less than one year, with few patients deriving long-term benefit.
For illustration, a randomized clinical trial involving over 500 patients with inoperable gastric cancer directly compared Mutamycin®, Platinol® and 5-FU to Ellence®, Platinol® and 5-FU chemotherapy. Patients receiving the Mutamycin®-based regimen had an average survival of 9.4 months, compared to 8.8 months for those receiving the Ellence®-based regimen.
Results from several clinical trials have also indicated that the chemotherapy agent Taxotere® has significant anti-cancer activity in gastric cancer. Two separate clinical trials conducted in Europe evaluated the combination of Taxotere® and Platinol® in patients with locally advanced and metastatic gastric cancer. Overall anti-cancer response rates ranged from 37% to 56% and the average survival duration was approximately 9 to 10 months. Higher doses of Taxotere® resulted in improved treatment outcomes.
Researchers from Italy conducted another clinical trial evaluating Taxotere® as a single agent following the chemotherapy combination consisting of Platinol®, Ellence®, fluorouracil and leucovorin (PELF) in patients with locally advanced and metastatic gastric cancer. The overall anti-cancer response rate following PELF was 40% which was improved to almost 58% after Taxotere® administration. This is nearly a 50% increase in anti-cancer responses with the addition of single agent Taxotere®. Patients with inoperable stage III gastric cancer should consider participating in clinical trials designed to evaluate new treatment approaches.
Chemotherapy and Radiation Therapy as Primary Treatment
Chemotherapy combined with radiation therapy and surgery has also been evaluated in patients with stage III gastric cancer. Anti-cancer response rates of over 50% and two-year survival without cancer progression of around 30% have been reported. It appears that the combination of chemotherapy and radiation therapy has substantial activity for the local control of advanced gastric cancer. To learn more, go to Radiation Therapy for Gastric Cancer.
Strategies to Improve Treatment
The progress that has been made in the treatment of gastric cancer has resulted from the use of multi-modality treatment and improved patient and physician 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.
New Adjuvant Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies is an active area of clinical research carried out in phase II clinical trials. Adjuvant therapy may consist of chemotherapy alone or in combination with radiation therapy or biological agents.
Chemotherapy Combined with Biologic Agents: Combining chemotherapy with biologic agents is the focus of intensive investigation and there are many such clinical trials ongoing in patients with other cancers.
In a recent clinical trial, the regimen of hydroxyurea, fluorouracil, and Interferon was evaluated in 30 patients with advanced gastric cancer. There were 2 complete (7%) and 11 (37%) partial responses. This response rate is as good or better than any other previously reported regimen, suggesting some activity for Interferon for the treatment of gastric cancer.
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. With the development of new chemotherapy regimens and radiation therapy, clinical trials of neoadjuvant therapy performed in patients with gastric cancer are currently ongoing.
Multiple Drug Resistance Inhibitors: Gastric cancer can be drug resistant at the outset of treatment or develop drug resistance after treatment. Several drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in esophageal cancer and other cancers.
Gene Therapy: Currently, there are no gene therapies approved for the treatment of gastric cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunction gene or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer death or efforts to make the immune system kill cancer cells. A few gene therapy studies are being carried out in patients with refractory gastric cancer. If successful, these therapies could be applied to patients with earlier stage disease.