Prognostic Implications of Lateral Lymph Nodes in Rectal Cancer: A Population-Based Cross-sectional Study With Standardized Radiological Evaluation After Dedicated Training

Background: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter, and location of lateral lymph nodes.Objective: To analyze lateral lymph node characteristics, the role of downsizing on restaging MRI, and associated local recurrence rates for patients with cT3-4 rectal cancer after MRI re-review and training.Design: Retrospective population-based cross-sectional study.Settings: This collaborative project was led by local investigators from surgery and radiology departments in 60 Dutch hospitals.Patients: A total of 3057 patients underwent rectal cancer surgery in 2016: 1109 had a cT3-4 tumor located <= 8 cm from the anorectal junction, of whom 891 received neoadjuvant therapy.Main outcome measures: Local recurrence and (ipsi) lateral local recurrence rates.Results: Re-review identified 314 patients (35%) with visible lateral lymph nodes. Of these, 30 patients had either only long-stretched obturator (n = 13) or external iliac (n = 17) nodes, and both did not lead to any lateral local recurrences. The presence of internal iliac/obturator lateral lymph nodes (n = 284) resulted in 4-year local recurrence and lateral local recurrence rates of 16.4% and 8.8%, respectively. Enlarged (>= 7 mm) lateral lymph nodes (n = 122) resulted in higher 4-year local recurrence (20.8%, 13.1%, 0%; p <.001) and lateral local recurrence (14.7%, 4.4%, 0%; p < 0.001) rates compared to smaller and no lateral lymph nodes, respectively. Visible lateral lymph nodes (HR 1.8 [1.1-2.8]) and enlarged lateral lymph nodes (HR 1.9 [1.1-3.5]) were independently associated with local recurrence in multivariable analysis. Enlarged lateral lymph nodes with malignant features had higher 4-year lateral local recurrence rates of 17.0%. Downsizing had no impact on lateral local recurrence rates. Enlarged lateral lymph nodes were found to be associated with higher univariate 4-year distant metastasis rates (36.4% vs 24.4%; p = 0.021), but this was not significant in multivariable analyses (HR 1.3 [0.9-1.]) and did not worsen overall survival.Limitations: This study was limited by the retrospective design and total number of patients with lateral lymph nodes.Conclusions: The risk of lateral local recurrence due to (enlarged) lateral lymph nodes was confirmed, but without the prognostic impact of downsizing after neoadjuvant therapy. These results point toward the incorporation of primary lateral lymph node size into treatment planning. See Video Abstract