Chemoradiotherapy alone vs. chemoradiotherapy and hysterectomy for locally advanced cervical cancer: A systematic review and updated meta-analysis

The benefit of adjuvant hysterectomy after definitive concurrent chemoradiotherapy (CCRT) for locally-advanced cervical cancer (LACC) is controversial. The purpose of the present study was to systematically search the literature and perform a meta-analysis to compare overall survival (OS) and disease-free survival (DFS) between patients subjected to CCRT with hysterectomy and those who underwent CCRT alone. The PubMed, Scopus, Embase and Google scholar databases were searched. A meta-analysis to determine hazard ratios (HRs) and odds ratios (ORs) with meta-regression was performed for the following moderators: Disease stage, histology and proportion of radical hysterectomy. Data from 14 studies were included. The results indicated that patients who received CCRT with hysterectomy had significantly better OS (HR, 0.72; 95% CI, 0.56 to 0.91; I(2)=19%; P=0.007) and DFS (HR, 0.72; 95% CI, 0.56 to 0.93; I(2)=27%; P=0.01) than those treated with CCRT alone. However, in a subgroup analysis by study type, the results were significant only for retrospective studies but not for randomized controlled trials (RCTs). However, only 2 RCTs were included with small sample size, heterogeneity and low overall quality. Subgroup analyses based on the use of brachytherapy in the CCRT with hysterectomy group demonstrated no difference in OS and DFS between the two groups. Regarding the absolute numbers of death and recurrence events, no significant difference in mortality (OR, 0.91; 95% CI, 0.62 to 1.33; I(2)=0%; P=0.64) was determined between the two groups, but a significantly reduced incidence of recurrence was observed in the CCRT with hysterectomy group (OR, 0.61; 95% CI, 0.47-0.79; I(2)=29%; P=0.0002). The meta-regression results point to a significant influence of the proportion of stage II patients on OS. Despite the overall analysis indicating improved OS and DFS with the use of adjuvant hysterectomy after CCRT, subgroup analysis based on similar treatment protocols failed to demonstrate any significant benefit of hysterectomy in LACC. However, the results indicated that the recurrence rate may be higher in patients undergoing CCRT without hysterectomy. The limited quality of the studies included and selection bias from retrospective studies restrict the possibility to draw strong conclusions.