Therapeutic role of para-aortic lymphadenectomy in patients with intermediate- and high-risk endometrial cancer: a systematic review and meta-analysis

Objective Lymph nodal involvement is a prognostic factor in endometrial cancer. The added value of para-aortic lymphadenectomy compared with pelvic nodal evaluation alone remains a matter of debate in the management of patients with intermediate- and high-risk endometrial cancer. A systematic review and meta-analysis was conducted to assess the prognostic value of para-aortic lymphadenectomy in terms of overall survival and disease-free survival in patients with intermediate- and high-risk endometrial cancer. Methods The study adhered to the PRISMA guidelines. PubMed, Google Scholar and ClinicalTrials.gov were searched from January 2000 to April 2023. Studies on intermediate- and high-risk patients who underwent pelvic versus pelvic and para-aortic dissection were included in the analysis. The Methodological Index for Nonrandomized Studies (MINORS) and the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) were used for quality assessment of the selected articles. Results Fourteen studies were identified, encompassing 9415 patients with a median age of 62 years (IQR 56.5-66.5). The majority had International Federation of Gynecology and Obstetrics stage I-II disease (76%) and endometrioid histology (89%). The 72% of patients who underwent only pelvic nodal evaluation and the 87% who underwent pelvic and para-aortic lymphadenectomy received adjuvant treatment (p=0.44). Pelvic and para-aortic lymphadenectomy was associated with a significant improvement in 5-year overall survival (RR=0.71, 95% CI 0.57 to 0.88, p<0.01), translating to a 41% reduction in the risk of overall death. However, no significant differences were observed in the 5-year risk of recurrence (RR=1.12, 95% CI 0.94 to 1.34, p=0.15). Additionally, patients undergoing pelvic and para-aortic lymphadenectomy experienced a 26% increased risk of post-operative complications (RR=1.26, 95% CI 1.04 to 1.53, p=0.03) and prolonged operative times (MD=56.27, 95% CI 15.94 to 96.60, p<0.01). Conclusion Pelvic and para-aortic lymphadenectomy appears to confer a prognostic benefit in patients with intermediate- and high-risk endometrial cancer. Robust prospective studies are needed to further validate these findings and elucidate the precise role of para-aortic lymphadenectomy in the optimal management of these patients.