Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer

Background: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs. Methods: PubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed. Results: Seven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3–15%) compared to LLND- (11–27%; RR = 0.40, 95%CI [0.25–0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61–78% vs. 46–79% for LLND-; RR = 0.72, 95%CI [0.51–1.02], p = 0.143), and neither was five-year OS (range 69–91% vs. 72–80%; RR = 0.72, 95%CI [0.45–1.14], p = 0.163). Conclusion: In rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND.