High dose rate versus low dose rate intracavity brachytherapy for locally advanced uterine cervix cancer

Background This is an updated version of the original Cochrane review published in 2010 (Issue 7). Carcinoma of the uterine cervix is the second most common cancer and the third leading cause of cancer death among women. Radiotherapy has been used successfully to treat cervical cancer for nearly a century. The combination of external beam radiotherapy (EBRT) and intracavity brachytherapy (ICBT) has become a standard treatment for cervical cancer. Whether high dose rate (HDR) or low dose rate (LDR) brachytherapy improves outcomes in terms of local control rates, survival and complications for women with cervical cancer remains controversial. Objectives To assess the efficacy and safety of HDR versus LDR ICBT in combination with EBRT for women with uterine cervical cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (1966 to March 2014), EMBASE (1974 to March 2014), and the Chinese Biomedical Literature Database (CBM) (1978 to March 2014) for relevant original, published trials. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs that compared HDR with LDR ICBT, combined with EBRT, for women with locally advanced uterine cervical cancer. Data collection and analysis Two authors independently extracted the data using standardised forms. Primary outcome measures included overall survival (OS), relapse-free survival (RFS) and pelvic control rate, while secondary outcomes included rates of recurrence and complications. Main results Four studies involving 1265 women met the inclusion criteria. In our meta-analysis to compare HDR and LDR ICBT, the pooled risk ratios (RRs) were 0.95 (95% confidence interval (CI) 0.79 to 1.15), 0.93 (95% CI 0.84 to 1.04) and 0.79 (95% CI 0.52 to 1.20) for 3, 5-and 10-year overall survival rates respectively; and 0.95 (95% CI 0.84 to 1.07) and 1.02 (0.88 to 1.19) for 5-and 10-year disease-specific survival (DSS) rates respectively. The RR for RFS was 1.04 (95% CI 0.71 to 1.52) and 0.96 (95% CI 0.81 to 1.14) at 3-and 5-years. For local control rates the RR was 0.95 (95% CI 0.86 to 1.05) and 0.95 (95% CI 0.87 to 1.05) at 3-and 5-years; with a RR of 1.09 (95% CI 0.83 to 1.43) for locoregional recurrence, 0.79 (95% CI 0.40 to 1.53) for local and distant recurrence, 2.23 (95% CI 0.78 to 6.34) for para-aortic lymph node metastasis, and 0.99 (95% CI 0.72 to 1.35) for distance metastasis. For bladder, rectosigmoid and small bowel complications, the RR was 1.33 (95% CI 0.53 to 3.34), 1.00 (95% CI 0.52 to 1.91) and 3.37 (95% CI 1.06 to 10.72) respectively. These results indicated that there were no significant differences except for increased small bowel complications with HDRs (P = 0.04). Authors' conclusions Since the last version of this review, no new studies were identified for inclusion in this review to provide additional information. This review showed no significant differences between HDR and LDR ICBT when considering OS, DSS, RFS, local control rate, recurrence, metastasis and treatment related complications for women with cervical carcinoma. Due to some potential advantages of HDR ICBT (rigid immobilization, outpatient treatment, patient convenience, accuracy of source and applicator positioning, individualized treatment) we recommend the use of HDR ICBT for all clinical stages of cervix cancer. The overall risk of bias was high for the included studies as many of the items were either of high or unclear risk. The GRADE assessment of the quality of the evidence was low to moderate.