Neoadjuvant chemotherapy for locally advanced cervical cancer: a systematic review and meta-analysis of individual patient data from 21 randomised trials

Abstract

Despite the enrollment of more than 3000 women in randomised trials, the benefits and risks of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer remain uncertain. We carried out a systematic review and meta-analysis of individual patient data to assess the effect of neoadjuvant chemotherapy in two comparisons. In the first comparison, of neoadjuvant chemotherapy followed by radical radiotherapy compared with the same radiotherapy alone, we obtained data from 18 trials and 2074 patients. When all trials were considered together, a high level of statistical heterogeneity suggested that the results could not be combined indiscriminately. A substantial amount of heterogeneity was explained by separate analyses of groups of trials. Trials using chemotherapy cycle lengths of 14 days and shorter (Hazard Ratio (HR))=0.83, 95% Confidence Interval (CI)=0.69-1.00, P=0.046) or cisplatin dose intensities greater than or equal to 25 mg/m2 per week (HR=0.91, 95% CI=0.78-1.05, P=0.20) tended to show an advantage for neoadjuvant chemotherapy on survival. In contrast, trials using cycle lengths longer than 14 days (HR=1.25, 95% CI=1.07-1.46, P=0.005) or cisplatin dose intensities lower than 25mg/m2 per week (HR=1.35, 95% CI=1.11-1.14, P=0.002) tended to show a detrimental effect of neoadjuvant chemotherapy on survival. In the second comparison, of neoadjuvant chemotherapy followed by surgery compared with radical radiotherapy alone, data from 5 trials and 872 patients were obtained. The combined results from all trials (HR=0.65, 95% CI=0.53-0.80, P=0.0004) indicated a highly significant reduction in the risk of death with neoadjuvant chemotherapy, but there were some differences between the trials in their design and results. Despite some unexplained heterogeneity, the timing and dose intensity of cisplatin-based neoadjuvant chemotherapy appears to have an important impact on whether or not it benefits women with locally advanced cervical cancer and warrants further exploration.