Traditional and Cumulative Meta-analysis: Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Resectable Esophageal Carcinoma

The role of neoadjuvant chemoradiotherapy followed by surgery (CRTS) compared with surgery alone (SA) for resectable esophageal carcinoma has been established by several randomized controlled trials (RCTs). The present study aimed to investigate the difference in survival between the two treatments by a review of meta-analyses. Related research indicators were extracted from RCTs investigating CRTS or SA for resectable esophageal carcinoma by searching electronic databases for eligible articles. Outcomes were synthesized by adopting a fixed- or random-effects model with 95% confidence interval (CI). A total of 22 RCTs including 3,419 patients were selected. The odds ratio (OR) (95% CI, P-value), expressed as CRTS vs. SA, was 1.06 (0.94-1.19, P=0.348) for 1-year overall survival rate (OSR1y), 1.38 (1.20-1.58, P<0.001) for 3-year overall survival rate (OSR3y), and 1.42 (1.22-1.66, P<0.001) for 5-year overall survival rate (OSR5y). The R0 resection rate increased in patients treated by CRTS (OR=2.76, 95% CI: 2.15-3.53, P<0.001). CRTS lowered the locoregional cancer recurrence (OR=0.49, 95% CI: 0.36-6.65, P<0.001) and distant metastasis rate (OR=0.76, 95% CI: 0.60-0.97, P=0.02). However, the incidence of postoperative mortality was similar between the two groups (OR=0.97, 95% CI: 0.72-1.32, P=0.87). The subgroup analysis revealed that OSR3y and OSR5y for Asian, European and American populations were significantly higher in the CRTS group compared with those in the SA group (P<0.05). When comparing the OSR1y between the two groups for patients in all three continents, there was no significant difference (P>0.05). Histological subgroup analysis indicated that patients with esophageal adenocarcinoma may benefit from CRTS in terms of OSR1y (OR=1.55, 95% CI: 1.09-2.20, P=0.01), OSR3y (OR=1.77, 95% CI: 1.34-2.36, P<0.0001) and OSR5y (OR=1.92, 95% CI: 1.34-2.75, P=0.0004). The pooled OR of squamous cell carcinoma in terms of OSR3y and OSR5y between the two groups was 1.57 (95% CI: 1.21-2.04, P=0.0006) and 1.69 (95% CI: 1.32-2.16, P<0.0001), respectively, but there was no statistical difference in terms of OSR1y (OR=1.13, 95% CI: 0.88-1.45, P=0.35). Thus, neoadjuvant CRT followed by surgery may improve long-term survival and surgical parameters, and reduce locoregional cancer recurrence and distant metastasis.