Abstract
INTRODUCTION: Treatment guidelines for colorectal cancer (CRC) suggest 2 classifications for histological differentiation-highest grade and predominant. However, the optimal predictor of lymph node metastasis (LNM) in T1 CRC remains unknown. This systematic review aimed to evaluate the impact of the use of highest-grade or predominant differentiation on LNM determination in T1 CRC. METHODS: The study protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD42023416971) and was published in OSF ( https://osf.io/TMAUN/ ) on April 13, 2023. We searched 5 electronic databases for studies assessing the diagnostic accuracy of highest-grade or predominant differentiation to determine LNM in T1 CRC. The outcomes were sensitivity and specificity. We simulated 100 cases with T1 CRC, with an LNM incidence of 11.2%, to calculate the differences in false positives and negatives between the highest-grade and predominant differentiations using a bootstrap method. RESULTS: In 42 studies involving 41,290 patients, the differentiation classification had a pooled sensitivity of 0.18 (95% confidence interval [CI] 0.13-0.24) and 0.06 (95% CI 0.04-0.09) ( P < 0.0001) and specificity of 0.95 (95% CI 0.93-0.96) and 0.98 (95% CI 0.97-0.99) ( P < 0.0001) for the highest-grade and predominant differentiations, respectively. In the simulation, the differences in false positives and negatives between the highest-grade and predominant differentiations were 3.0% (range 1.6-4.4) and -1.3% (range -2.0 to -0.7), respectively. DISCUSSION: Highest-grade differentiation may reduce the risk of misclassifying cases with LNM as negative, whereas predominant differentiation may prevent unnecessary surgeries. Further studies should examine differentiation classification using other predictive factors.