Introduction

The implementation of the national bowel-screening program for colorectal cancer has had a significant impact on detecting early colorectal cancer (pT1 & pT2 carcinomas). In recent decades, there has been a shift towards minimally invasive approaches for treating T1 colon carcinomas (CC), favoring local resection techniques over major surgeries. It is unknown whether risk stratification could establish organ preservation in T2 CC.

Aims & Methods

We aimed to evaluate the incidence of lymph node metastases (LNMs) in patients with pT2 CC in the Netherlands and to develop a prediction model to estimate the risk of LNMs which could be helpful to compare the risk of LNMs against the age-specific adverse events associated with segmental surgery. A retrospective nationwide cohort study was performed including all consecutive patients diagnosed with pT2 CC who underwent (completion) surgery between 2012 and 2020 in the Netherlands. Patients were identified by use of the Dutch ColoRectal Audit (DCRA). Exclusion criteria were: (1) neoadjuvant therapy; (2) synchronous CRC; (3) hereditary predisposition (4) history of IBD; and (5) non-adenocarcinoma. Data obtained from the DCRA were linked to the Dutch Nationwide Pathology Databank (PALGA). A subgroup analysis was conducted on patients up to 70 years old, who were treated between 2018 and 2020, to examine the association between mismatch repair (MMR) status and the presence of LNMs. Predictive factors for LNMs were evaluated with univariate- and multivariate logistic regression. Four machine learning (ML) models were developed and validated to predict LNM, including generalized linear modeling (GLM), GLM-Least Absolute Shrinkage and Selection Operator (GLM-LASSO), random forest (RF), and gradient boosting (XGB).

Results

In total 9,803 patients were included. The overall 30-day complication and mortality rates were 25.2% and 2.2%, respectively. In elderly patients (age ≥ 74), the complication and mortality rates increased to 30%, and 3.5%, respectively. LNMs were found in 1877 out of 9803 patients (19.1%). Younger age (OR 0.98, 95% CI 0.979 ─ 0.990), left-sided CC (OR 1.5, 95% CI 1.4-1.7), poor differentiation (1.7, 95% CI 1.4-2.2), and lymphovascular invasion (LVI) (OR 4.1, 95% CI 3.6-4.7) were independent risk factors for LNMs. In the subgroup analysis, deficient MMR (dMMR) status was found to be associated with a significantly lower risk of LNMs (OR 0.3, 95% CI 0.2-0.5). GLM demonstrated the highest prediction accuracy, achieving AUCs of 0.67 for the full model and 0.68 for the model focusing on patients up to 70 years old. The risk of LNMs in the lower-risk group (age ≥ 74, right-sided CC, LVI absent, good/moderate tumor differentiation) was 10.7%. In the absence of other risk factors, patients with a dMMR carcinoma had a risk of LNMs of 6.1%.

Conclusion

The predicted probability of LNMs should be balanced against the risks associated with segmental colon surgery. The findings of this study could serve as valuable guidance for clinicians, enabling them to inform patients about these competing risks before making a shared decision.