Multidisciplinary treatment for locally advanced gastric cancer: A systematic review and network meta-analysis

INTRODUCTION: This study aimed to evaluate the efficacy of multidisciplinary treatment for patients with locally advanced gastric cancer (LAGC) who underwent radical gastrectomy. PATIENTS AND METHODS: Randomised controlled trials (RCTs) comparing the effectiveness of surgery alone, adjuvant chemotherapy (CT), adjuvant radiotherapy (RT), adjuvant chemoradiotherapy (CRT), neoadjuvant CT, neoadjuvant RT, neoadjuvant CRT, perioperative CT and hyperthermic intraperitoneal chemotherapy (HIPEC) for LAGC were searched. Overall survival (OS), disease-free survival (DFS), recurrence and metastasis, long-term mortality, adverse events (grade ≥3), operative complications and R0 resection rate were used as outcome indicators for meta-analysis. RESULTS: Forty-five RCTs with 10077 participants were finally analysed. Adjuvant CT had higher OS (hazard ratio [HR] = 0.74, 95% credible interval [CI] = 0.66–0.82) and DFS (HR = 0.67, 95% CI = 0.60–0.74) than surgery-alone group. Perioperative CT (odds ratio [OR] = 2.56, 95% CI = 1.19–5.50) and adjuvant CT (OR = 0.48, 95% CI = 0.27–0.86) both had more recurrence and metastasis than HIPEC + adjuvant CT, while adjuvant CRT tended to have less recurrence and metastasis than adjuvant CT (OR = 1.76, 95% CI = 1.29–2.42) and even adjuvant RT (OR = 1.83, 95% CI = 0.98–3.40). Moreover, the incidence of mortality in HIPEC + adjuvant CT was lower than that in adjuvant RT (OR = 0.28, 95% CI = 0.11–0.72), adjuvant CT (OR = 0.45, 95% CI = 0.23–0.86) and perioperative CT (OR = 2.39, 95% CI = 1.05–5.41). Analysis of adverse events (grade ≥3) showed no statistically significant difference between any two adjuvant therapy groups. CONCLUSION: A combination of HIPEC with adjuvant CT seems to be the most effective adjuvant therapy, which contributes to reducing tumour recurrence, metastasis and mortality – without increasing surgical complications and adverse events related to toxicity. Compared with CT or RT alone, CRT can reduce recurrence, metastasis and mortality but increase adverse events. Moreover, neoadjuvant therapy can effectively improve the radical resection rate, but neoadjuvant CT tends to increase surgical complications.