The impact of para-aortic lymph node irradiation on disease-free survival in patients with cervical cancer: A systematic review and meta-analysis

BACKGROUND: Patients with locally advanced cervical cancer without para-aortic lymph node metastases (PAO-LNM) at diagnosis who undergo concurrent chemoradiotherapy are at 4–11% risk of developing PAO-LNM during follow-up. Some studies suggest a beneficial influence of elective para-aortic radiotherapy (PAO-RT) on disease-free survival (DFS) in these patients. The aim of this study was to systematically review and meta-analyse literature on the impact of PAO-RT on DFS in cervical cancer patients. METHODS: A systematic search of PubMed/MEDLINE and EMBASE databases was performed. The analysis included intervention studies that reported on DFS in patients with cervical cancer who received chemotherapy and pelvic radiotherapy with or without PAO-RT. From each included study, relevant study characteristics and outcome data including the hazard ratio (HR) adjusted for potential confounders were extracted. An overall pooled adjusted hazard ratio (aHR) for DFS after PAO-RT versus no PAO-RT was calculated using a random-effects model. RESULTS: A total of 2,016 articles were evaluated. Eleven articles were included in the systematic review, of which 3 were appropriate for quantitative meta-analysis. Pooling of these 3 cohorts (including 1,113 patients) demonstrated a statistically significant association between PAO-RT and DFS (pooled aHR 0.87, 95% confidence interval: 0.79–0.97). No significant heterogeneity among reported aHRs was observed (I(2) = 0.0%). CONCLUSIONS: This meta-analysis suggests a modest but significant beneficial impact of elective para-aortic radiotherapy on DFS in patients with locally advanced cervical cancer who undergo concurrent chemoradiotherapy. This finding based on non-randomized studies provides an imperative for further investigation in prospective controlled trials.