Patients who have gastric cancer surgery followed by chemotherapy have an associated decreased risk of death and improved disease-free survival compared to patients who have surgery alone, according to an analysis of previous studies, reported in the May 5 issue of JAMA.
Gastric cancer is a common and highly fatal disease, with current 5-year survival rates less than 20 percent, according to background information in the article. "Surgery for disease at an early stage can usually be performed with curative intent, but the 5-year survival rate is disappointing. Over the last 3 decades, numerous phase 3 studies including a surgery-only group have been reported, but definitive evidence of the efficacy of adjuvant [after surgery] chemo¬therapy is lacking," the authors write.
Xavier Paoletti, Ph.D., of the Institut National du Cancer, Boulogne, France, and colleagues with the Global Advanced/Adjuvant Stomach Tumor Research International Collaboration (GASTRIC) Group, assessed the benefit of adjuvant chemotherapy quantitatively through a meta-analysis based on individual patient data from all relevant trials. For this analysis, the researchers identified 31 eligible trials (6,390 patients). As of 2010, individual patient data were available from 17 trials (3,838 patients representing 60 percent of the targeted data) with a median (midpoint) follow-up exceeding 7 years.
There were 1,000 deaths among 1,924 patients assigned to chemotherapy groups and 1,067 deaths among 1,857 patients assigned to surgery-only groups. The researchers found that there was a significant benefit from any chemotherapy compared with surgery alone, with analysis indicating an overall 18 percent reduction in the risk of death with chemotherapy. The estimated median overall survival was 4.9 years in the surgery-only group vs. 7.8 years in the group receiving adjuvant chemotherapy. An absolute improvement of about 6 percent in overall survival was observed after 5 years, and maintained at 10 years. Five-year overall survival increased from 49.6 percent to 55.3 percent with chemotherapy. Adjuvant chemotherapy was also associated with an 18 percent reduction in the risk of relapse, compared with surgery alone.
"In conclusion, this patient-level meta-analysis shows that adjuvant fluorouracil-based chemotherapy, even in monotherapy, is associated with improvement in overall survival and is recommended for patients who have not received perioperative treatments after complete resection of their gastric cancer. Future reports based on data being collected will explore prognostic factors and the surrogacy of disease-free survival for overall survival in this population," the authors write.
Editorial: Gastric Cancer - An Enigmatic and Heterogeneous Disease
In an accompanying editorial, Manish A. Shah, M.D., of Memo¬rial Sloan Kettering Cancer Center, New York, and Jaffer A. Ajani, M.D., of the University of Texas M. D. Anderson Cancer Center, Houston, comment on the findings of these studies on gastric cancer.
Regarding the study by Anderson and colleagues, "These findings have important implications. The distinction between cardia and noncardia gastric cancer is relevant to the role of H pylori carcinogenesis. The pathogenesis of noncardia cancer follows a multistep progression that is likely initiated by chronic inflammation. The disease progresses through chronic gastritis [inflammation of the lining of the stomach], intestinal metaplasia, and dysplasia [abnormal cells]. Although H pylori gastritis contributes to the risk of noncardia adenocarcinoma, it may be protective for proxi¬mal adenocarcinoma. Furthermore, gene-environmen¬tal interaction may influence susceptibility to the consequences of H pylori gastritis."
Drs. Shah and Ajani ask if the large sample size of the GASTRIC meta-analysis can overcome heterogeneity in biology, therapy, or both. "The answer to this question is not known. However, based on the available data, postoperative adjuvant chemotherapy cannot be recommended as another standard to most Western patients with high-risk gastric cancer. Efforts should be invested in designing and executing well-conceived randomized controlled trials that answer ques¬tions for specific subsets of patients."
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