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Meta-Analysis
. 2024 Mar 1;15(3):e00673.
doi: 10.14309/ctg.0000000000000673.

Diagnostic Accuracy of Highest-Grade or Predominant Histological Differentiation of T1 Colorectal Cancer in Predicting Lymph Node Metastasis: A Systematic Review and Meta-Analysis

Jun Watanabe  1   2 , Katsuro Ichimasa  3   4 , Yuki Kataoka  5   6   7   8 , Shoko Miyahara  9 , Atsushi Miki  1 , Khay Guan Yeoh  4   10 , Shigeo Kawai  11 , Fernando Martínez de Juan  12   13   14 , Isidro Machado  15   16 , Kazuhiko Kotani  2 , Naohiro Sata  1
Affiliations
Meta-Analysis

Diagnostic Accuracy of Highest-Grade or Predominant Histological Differentiation of T1 Colorectal Cancer in Predicting Lymph Node Metastasis: A Systematic Review and Meta-Analysis

Jun Watanabe et al. Clin Transl Gastroenterol. .

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.

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Conflict of interest statement

Guarantor of the article: Jun Watanabe, MD, PhD.

Specific author contributions: J.W., K.I., and Y.K.: contributed to the study concept and design and drafting of the manuscript. J.W.: obtained funding. J.W., K.I., Y.K., S.M., A.M., and K.G.Y.: contributed to the statistical analysis and interpretation of data. K.K. and N.S.: contributed to administrative support and study supervision. J.W., K.I., and Y.K.: developed the software. J.W., K.I., Y.K., S.M., A.M., K.G.Y., F.M.d.J., and I.M.: contributed to data collection and critical revision of the manuscript. S.K., K.K., and N.S.: contributed to critical revision of the manuscript.

Financial support: The study was supported by JSPS KAKENHI (grant number JP21K21121 and 23K16289).

Potential competing interests: None to report.

Figures

Figure 1.
Figure 1.
Flowchart of the study selection process.
Figure 2.
Figure 2.
Forest plot for the proportion of lymph node metastasis in T1 colorectal cancer. ES, effect size; CI, confidence interval.
Figure 3.
Figure 3.
Forest plot showing the sensitivity and specificity of the highest-grade and predominant histological differentiations for prediction of lymph node metastasis. CI, confidence interval.
Figure 4.
Figure 4.
Forest plot for the subgroup analysis according to region (Japan and other countries) regarding highest-grade differentiation. CI, confidence interval.
Figure 5.
Figure 5.
Forest plot for the subgroup analysis according to region (Japan and other countries) regarding predominant differentiation. CI, confidence interval.
See this image and copyright information in PMC

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