The prognostic impact of lymph node yield in deficient and proficient mismatch repair colon cancers: A retrospective national cohort study

Introduction: Lymph node yield (LNY) is a recognised prognostic factor in patients with colon cancer. Recent studies suggest LNY may reflect anti-tumour immune responses rather than surgical quality. Given the recognised difference in anti-tumour immunity according to mismatch repair (MMR) status, this study investigated whether LNY and its association with prognosis differed between colon cancers with deficient MMR (dMMR) and proficient MMR (pMMR). 

Methods: A national retrospective cohort study using the Danish Colorectal Cancer Group (DCCG) database. Patients diagnosed with new Stage I–III colon cancers undergoing potentially curative left or right hemicolectomies between 2016 and 2022 were included. The primary outcome was LNY according to MMR status. 

Results: In total of 9705 patients were included, of whom 7175 had pMMR cancers (74%). Median LNY for the whole cohort was 27. LNY <12 was seen in 178 patients (2%). dMMR cancers had higher median LNY (28 vs. 26 nodes, p < 0.001), and more patients with LNY ≥22 (73% vs. 66%, p < 0.001). No difference in the number of lymph node metastases was seen between groups. LNY <12 was associated with poorer overall survival (OS) regardless of MMR status and was independently associated with all-cause mortality. However, this effect was more marked in patients with dMMR than pMMR cancers {hazard ratio (HR) 4.23 (95% confidence interval [CI] 2.42–7.41) vs. 1.94 (1.21–3.13)}. 

Conclusion: LNY was significantly higher in dMMR cancers, where low LNY also has a stronger association with prognosis. These findings support the theory that LNY reflects anti-tumour immunity rather than surgical quality.