Adjuvant Systemic Therapy after Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis

Background: Standard of care for locally advanced cervical cancer is chemoradiation and brachytherapy. The addition of adjuvant systemic treatment may improve overall survival. A systematic review and meta-analysis was conducted to summarize evidence on survival outcomes, treatment completion and toxicity. Methods: PubMed, EMBASE and Web of Science were systematically searched for relevant prospective and retrospective studies. Two authors independently selected studies, extracted data and assessed study quality. Pooled hazard ratios for survival endpoints were estimated using random effect models. Weighted averages of treatment completion and toxicity rates were calculated and compared by the Fisher exact test. Results: The search returned 612 articles; 35 articles reporting on 29 different studies on adjuvant chemotherapy or immunotherapy were selected for systematic review. Twelve studies on an adjuvant platinum–pyrimidine antagonist or platinum–taxane were included for meta-analysis. The pooled hazard ratios for overall survival were 0.76 (99%CI: 0.43–1.34, p = 0.22) and 0.47 (99%CI: 0.12–1.86, p = 0.16) for the addition of, respectively, a platinum–pyrimidine antagonist or platinum–taxane to chemoradiation and brachytherapy. Completion rates were 82% (95%CI: 76–87%) for platinum–pyrimidine antagonist and 74% (95%CI: 63–85%) for platinum–taxane. Severe acute hematological and gastro-intestinal toxicities were significantly increased by adding adjuvant chemotherapy to chemoradiation and brachytherapy. Conclusions: The addition of adjuvant platinum–pyrimidine antagonist or platinum–taxane after chemoradiation and brachytherapy does not significantly improve overall survival, while acute toxicity is significantly increased. These adjuvant treatment strategies can therefore not be recommended for unselected patients with locally advanced cervical cancer.