Neoadjuvant chemotherapy followed by surgery versus surgery alone for gastric carcinoma: systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
The 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.


METHODS
We 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.


RESULTS
A 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.


CONCLUSIONS
NAC 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.
Anhui Medical University, Hefei, China ; Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
A-Man
AM
Xu
Anhui Medical University, Hefei, China ; Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Lei
L
Huang
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Wei
W
Liu
Anhui Medical University, Hefei, China ; Department of Medical Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Shuang
S
Gao
Anhui Medical University, Hefei, China ; Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Wen-Xiu
WX
Han
Anhui Medical University, Hefei, China ; Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Zhi-Jian
ZJ
Wei
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D006801:Humans; D020360:Neoadjuvant Therapy; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D015996:Survival Rate; D016896:Treatment Outcome