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Risk factors for lymph node metastasis in T2 colorectal cancer: a systematic review and meta-analysis

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Abstract

Background

Lymph node metastasis (LNM) occurs in 20–25% of patients with T2 colorectal cancer (CRC). Identification of risk factors for LNM in T2 CRC may help identify patients who are at low risk and thereby potential candidates for endoscopic full-thickness resection. We examined risk factors for LNM in T2 CRC with the goal of establishing further criteria of the indications for endoscopic resection.

Methods

MEDLINE, CENTRAL, and EMBASE were systematically searched from inception to November 2023. Studies that investigated the association between the presence of LNM and the clinical and pathological factors of T2 CRC were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Certainty of evidence (CoE) was assessed using the GRADE approach.

Results

Fourteen studies (8349 patients) were included. Overall, the proportion of LNM was 22%. The meta-analysis revealed that the presence of lymphovascular invasion (OR, 5.5; 95% CI 3.7–8.3; high CoE), high-grade tumor budding (OR, 2.4; 95% CI 1.5–3.7; moderate CoE), poor differentiation (OR, 2.2; 95% CI 1.8–2.7; moderate CoE), and female sex (OR, 1.3; 95% CI 1.1–1.7; high CoE) were associated with LNM in T2 CRC. Lymphatic invasion (OR, 5.0; 95% CI 3.3–7.6) was a stronger predictor of LNM than vascular invasion (OR, 2.4; 95% CI 2.1–2.8).

Conclusions

Lymphovascular invasion, high-grade tumor budding, poor differentiation, and female sex were risk factors for LNM in T2 CRC. Endoscopic resection of T2 CRC in patients with very low risk for LNM may become an alternative to conventional surgical resection.

Trial registration

PROSPERO, CRD42022316545.

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Data availability

The datasets analyzed in this study are available from the corresponding author on reasonable request.

Abbreviations

CI:

Confidence interval

CoE:

Certainty of the evidence

CRC:

Colorectal cancer

EID:

Endoscopic intermuscular dissection

eFTR:

Endoscopic full-thickness resection

LNM:

Lymph node metastasis

OR:

Odds ratio

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Acknowledgements

The authors thank the Japanese Society for Cancer of the Colon and Rectum; Dr. Yoshiki Kajiwara from the Department of Surgery, National Defense Medical College; Dr. Hirotoshi Kobayashi from the Department of Surgery, Teikyo University School of Medicine, Mizonokuchi Hospital; Dr. Naohisa Yoshida from the Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science; Dr. Koji Komori from the Department of Gastroenterological Surgery Aichi Cancer Hospital; and Dr. Tadahiko Masaki from Shimizugaoka Hospital for providing us with the detailed information necessary for this study. The authors also thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by JSPS KAKENHI grant number 22K16500.

Author information

Author notes

  1. Jun Watanabe and Katsuro Ichimasa are Co-first authors.

Authors and Affiliations

  1. Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan

    Jun Watanabe & Makiko Tahara

  2. Division of Community and Family Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan

    Jun Watanabe

  3. Digestive Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasaki-chuo, Tsuzuki, Yokohama, 224-8503, Japan

    Katsuro Ichimasa, Shin-ei Kudo, Kenichi Mochizuki & Yuki Takashina

  4. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Katsuro Ichimasa, Ker-Kan Tan & Khay Guan Yeoh

  5. Department of Surgery, National University Hospital, Singapore, Singapore

    Ker-Kan Tan

  6. Department of Internal Medicine, Kyoto Min-Iren Asukai Hospital, Kyoto, Japan

    Yuki Kataoka

  7. Section of Clinical Epidemiology, Department of Community Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Yuki Kataoka

  8. Scientific Research Works Peer Support Group (SRWS-PSG), Osaka, Japan

    Yuki Kataoka & Takafumi Kubota

  9. Department of Healthcare Epidemiology, Graduate School of Medicine / School of Public Health, Kyoto University, Kyoto, Japan

    Yuki Kataoka

  10. Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Takafumi Kubota

  11. Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore

    Khay Guan Yeoh

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  1. Jun Watanabe
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Contributions

JW, KI, SK, KM, and YK contributed to the study concept and design and the drafting of the manuscript. KI obtained funding. JW, KI, SK, KM, KT, YK, MT, TK, and YT contributed to the statistical analysis and interpretation of data. SK and KGY contributed to study supervision. JW, KI, SK, KM, KT, YK, MT, TK, and YT contributed to the data collection and critical revision of the manuscript.

Corresponding author

Correspondence to Katsuro Ichimasa.

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Watanabe, J., Ichimasa, K., Kudo, Se. et al. Risk factors for lymph node metastasis in T2 colorectal cancer: a systematic review and meta-analysis. Int J Clin Oncol (2024). https://doi.org/10.1007/s10147-024-02547-7

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