Neoadjuvant Chemotherapy Followed by Surgery versus Surgery Alone for Gastric Carcinoma: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

BackgroundThe effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC.MethodsWe systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed.ResultsA total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65–1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20–3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment.ConclusionsNAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with chemotherapy-related adverse effects as a drawback. This level 1a evidence doesn't support NAC to outweigh SA in terms of survival and surgical benefits when dealing with GC.

Does neoadjuvant/perioperative chemotherapy improve overall survival for T2N0 gastric adenocarcinoma?

“…A recent meta-analysis and a systematic review of NAC followed by surgery versus surgery alone were comprised of mostly small, single center trials with similarly limited proportions of T2N0 disease. 8,9 Contrary to the landmark trials, these pooled analyses did not show a benefit of NAC prior to surgery compared to surgery alone. However, other systemic reviews have shown an OS benefit for NAC.…”

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

“…Previous studies have established a key role of H. pylori in the pathogenesis of a variety of gastric diseases including gastritis, peptic ulcers, B lymphoma, and gastric cancer. [1][2][3][4]7,8 The impaired balance between H. pylori-producing aggressive bacterial endotoxins and host defensive mechanisms is critical in the different clinical outcomes observed in patients infected with this bug. Recently, we have reported that gastric fibroblasts can represent cellular target of H. pylori.…”

“…Furthermore, some patients lose the opportunity of curative resection resulting from the aggressive nature of GC. Although chemoradiotherapy and targeted therapy have confirmed an improvement in host response rates, the cancer recurrences and metastases are frequently observed 2, 3, 4, 5, 6. The bacteria Helicobacter pylori ( H. pylori) is one of the major risk factors for GC development.…”

“…Despite the incidence and mortality of gastric cancer (GC) have been decreasing, this disorder still remains one of the leading causes of cancer-related death rate worldwide. [1][2][3][4] Despite the fact that the adjuvant chemotherapy and surgical resection are the only curative therapies nowadays, most patients are diagnosed with an advanced stage of disease due to lack of specific early symptoms. Furthermore, some patients lose the opportunity of curative resection resulting from the aggressive nature of GC.…”

“…Although chemoradiotherapy and targeted therapy have confirmed an improvement in host response rates, the cancer recurrences and metastases are frequently observed. [2][3][4][5][6] The bacteria Helicobacter pylori (H. pylori) is one of the major risk factors for GC development. Epidemiology of H. pylori indicates that this bug colonizes the human stomach of about 50% of the world's population.…”