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

Background 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 intracavitary brachytherapy (ICBT) has become a standard treatment modality for cervical cancer. Depending on the difference in dose rate on 'Point A' (located 2 cm above the cervical os and 2 cm lateral to the central axis of the uterus), the ICBT is divided into three modalities: low dose rate (LDR), high dose rate (HDR) and medium dose rate (MDR). Despite the practical advantages of HDR, it is necessary to investigate further the efficacy and safety of HDR brachytherapy compared to LDR brachytherapy. Questions arise as to whether HDR or LDR brachytherapy improves results for patients with cervical cancer in terms of local control rates, survival and complications related to treatment. Objectives To assess the efficacy and safety of HDR-versus LDR-ICBT for patients with uterine cervical cancer. Search strategy We searched the Cochrane Gynaecological Cancer Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (1966 to November 2009), EMBASE (1974 to November 2009), Chinese Biomedical Literature Database (CBM) (1978 to November 2009) for relevant original, published trials. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs that compared HDR- with LDR-ICBT, combined with EBRT, for patients 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 patients met the inclusion criteria. In our meta-analysis to compare HDR and LDR, the pooled RRs were 0.95 (95% 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; 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. 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 three and five 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 three and five 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 distance 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 indicate that there were no significant differences except for increased small bowel complications with HDR (P = 0.04). Authors' conclusions 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.