Risk of Lymph Node Metastasis in T2 Colon Cancer: A Nationwide Population-Based Cohort Study

BACKGROUND: Similar to T1 colon cancer (CC), risk stratification may guide T2 CC treatment and reduce unnecessary major surgery. In this study, prediction models were developed that could identify T2 CC patients with a lower risk of lymph node metastasis (LNM) for whom (intensive) follow-up after local treatment could be considered.

METHODS: A nationwide cohort study was performed involving pT2 CC patients who underwent surgery between 2012 and 2020, using data from the Dutch ColoRectal Audit, which were linked to the Nationwide Pathology Databank. Four machine learning models were evaluated to predict LNM.

RESULTS: LNMs were found in 1877/9803 patients (19.1%). Independent risk factors included (younger) age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.979-0.990), left-sided CC (OR 1.5, 95% CI 1.4-1.7), poor differentiation (OR 1.7, 95% CI 1.4-2.2), and lymphovascular invasion (LVI; OR 4.1, 95% CI 3.6-4.7). A deficient mismatch repair (MMR) status significantly lowered the risk of LNM (OR 0.3, 95% CI 0.2-0.5). The general linear model demonstrated the highest prediction accuracy, achieving area under the receiver operating characteristic curves of 0.67 and 0.68, with good calibration. In the absence of risk factors, elderly patients (≥74 years of age) had a predicted risk of LNM of 10.7%, yet up to 30% experienced postoperative complications, with mortality rates reaching up to 3.5%. Patients with a deficient MMR status had a predicted risk of LNM of 6.1% if LVI was absent and the tumor was well-differentiated.

CONCLUSIONS: The risk of LNM should be weighed against surgical risks. The findings of this study will enable clinicians to make more deliberate considerations about these competing risks before making a shared decision.