Validity of combination active specific immunotherapy for colorectal cancer: a meta-analysis of 2993 patients

Abstract

Background aims: The aim of this study was to investigate whether active specific immunotherapy (ASI) is able to demonstrate therapeutic efficacy against colorectal cancer.

Methods: We conducted a systematic review of published papers from MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. Published data were extracted independently by two authors who used predefined database templates. The effects of ASI were compared with those of surgery alone, and a pooled analysis was performed with the use of the data from random- or fixed-effect models.

Results: Twelve trials matched our inclusion criteria (n = 2993, including 1842 control subjects). The overall analysis showed a significant survival benefit [1-, 2-, 3-, 4-, 5-, 6- and 7-year overall survival (OS), P < 0.05; 10-year OS, P < 0.001] in favor of ASI immunotherapy combined with surgery, but there was not an improvement in the 8- or 9-year OS (P > 0.05). The disease-free survival (DFS) rate was improved after the combination of ASI immunotherapy (2-, 3-, 5- and 10-year DFS, P < 0.05), but no significant improvement was noted for the 1-, 4-, 6-, 7-, 8- or 9-year DFS (P > 0.05). In addition, the disease-specific survival (DSS) was improved at some time points after the combination of ASI immunotherapy and surgery (2-, 3-, 4-, 5- and 6-year DSS, P < 0.05, but not the 1-, 7-, 8- or 9-year DSS, P > 0.05). An improved 2-, 3-, 4-, 5- and 6-year recurrence-free interval (RFI) (P < 0.05) was also observed in patients who received ASI therapy, but this was not observed for the 1-year RFI (P > 0.05). Furthermore, an analysis of the recurrence-free survival (RFS) showed that it was significantly increased in the ASI plus surgery group (1-, 2-, 3-, 4-, 5- and 6-year RFS, P < 0.001). The funnel plots showed that the analyses were relatively reliable and the publication bias was small.

Conclusions: The combination of ASI immunotherapy and surgery was superior in prolonging the overall survival time and enhancing the recurrence-free survival rate compared with surgery alone.

Keywords: Newcastle disease virus; active specific immunotherapy; bacillus Calmette-Guérin; colorectal cancer; meta-analysis.