New insights into tumor size in colorectal cancer: smaller size, higher risk?
- 1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center , ,
- 2Department of Colorectal Surgery, Changhai Hospital, Naval Medical University , ,
- 3Department of Pathology, Fudan University Shanghai Cancer Center , ,
Abstract
Background: In colorectal cancer, the AJCC T category is defined by the depth of bowel wall invasion rather than by the absolute size of the primary tumor. The clinical value of tumor size in assessing tumor aggressiveness, metastatic risk, and prognosis remains insufficiently investigated.
Aim: To evaluate the clinical value of tumor size in assessing potential metastatic risk and prognostic stratification in colorectal cancer.
Methods: We retrospectively included 10,513 patients with colorectal cancer who underwent surgical treatment at FUSCC between 2008 and 2020. We integrated tumor size with clinicopathological characteristics to assess metastatic risk using machine-learning models and SHAP-based interpretation. By modeling tumor size as both a categorical and continuous variable, we further investigated its prognostic relevance using Kaplan–Meier survival analysis and Cox proportional hazards regression incorporating restricted cubic splines. Additionally, an independent cohort of 6,739 patients from Changhai Hospital was used for external validation.
Results: Machine-learning identified lymph node metastasis as the primary predictive endpoint, with the CatBoost model achieving the highest AUROC of 0.800. SHAP analysis showed that smaller tumor diameter contributed positively to predicted metastatic risk. Multivariable restricted cubic spline analysis further demonstrated a significant nonlinear association between tumor diameter and OS, with mortality risk increasing as tumor diameter decreased within the approximately 0–3 cm range. Among younger male patients with locally advanced disease, tumors ≤3 cm were associated with significantly worse OS and DFS than tumors >5 cm (both P < 0.001). External validation yielded similar findings.
Conclusion: Smaller tumor size may paradoxically indicate higher lymph node metastatic risk and poorer prognosis in a subset of patients with colorectal cancer, particularly younger male patients with locally advanced disease. Tumor size may therefore serve as a complementary factor for postoperative risk stratification beyond conventional TNM staging.
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BibTeX
@article{ding2026insights,
title = {{New insights into tumor size in colorectal cancer: smaller size, higher risk?}},
author = {Ruipeng Ding and Tianyu Li and Cong Li and Wang Song and Xianhua Gao and Midie Xu and Sheng Wang},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1908104},
url = {https://europepmc.org/article/PMC/PMC13671944},
note = {CC BY},
}
RIS
TY - JOUR
TI - New insights into tumor size in colorectal cancer: smaller size, higher risk?
AU - Ruipeng Ding
AU - Tianyu Li
AU - Cong Li
AU - Wang Song
AU - Xianhua Gao
AU - Midie Xu
AU - Sheng Wang
PY - 2026
DA - 2026/10/02
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1908104
UR - https://europepmc.org/article/PMC/PMC13671944
AB - Background: In colorectal cancer, the AJCC T category is defined by the depth of bowel wall invasion rather than by the absolute size of the primary tumor. The clinical value of tumor size in assessing tumor aggressiveness, metastatic risk, and prognosis remains insufficiently investigated. Aim: To evaluate the clinical value of tumor size in assessing potential metastatic risk and prognostic stratification in colorectal cancer. Methods: We retrospectively included 10,513 patients with colorectal cancer who underwent surgical treatment at FUSCC between 2008 and 2020. We integrated tumor size with clinicopathological characteristics to assess metastatic risk using machine-learning models and SHAP-based interpretation. By modeling tumor size as both a categorical and continuous variable, we further investigated its prognostic relevance using Kaplan–Meier survival analysis and Cox proportional hazards regression incorporating restricted cubic splines. Additionally, an independent cohort of 6,739 patients from Changhai Hospital was used for external validation. Results: Machine-learning identified lymph node metastasis as the primary predictive endpoint, with the CatBoost model achieving the highest AUROC of 0.800. SHAP analysis showed that smaller tumor diameter contributed positively to predicted metastatic risk. Multivariable restricted cubic spline analysis further demonstrated a significant nonlinear association between tumor diameter and OS, with mortality risk increasing as tumor diameter decreased within the approximately 0–3 cm range. Among younger male patients with locally advanced disease, tumors ≤3 cm were associated with significantly worse OS and DFS than tumors >5 cm (both P < 0.001). External validation yielded similar findings. Conclusion: Smaller tumor size may paradoxically indicate higher lymph node metastatic risk and poorer prognosis in a subset of patients with colorectal cancer, particularly younger male patients with locally advanced disease. Tumor size may therefore serve as a complementary factor for postoperative risk stratification beyond conventional TNM staging.
SN - 2234-943X
ER -