Improving Colorectal Cancer Prognosis With Tumor Deposit-Based N-Staging

Tumor deposits are a key negative prognostic factor in colorectal cancer (CRC), yet their role in N-staging remains underexplored.¹ This study compared and validated 10 innovative models integrating tumor deposits, showing improved survival predictions over the traditional TNM system, though differences between models are modest.

This literature review is published in the European Journal of Surgical Oncology.

Novel models incorporating tumor deposits outperform tumor TNM in predicting outcomes. | Image credit: Ahmet Aglamaz - stock.adobe.com

“This study presents the first comprehensive external validation of novel N-staging models incorporating TDs [tumor deposits] compared to the gold standard N-staging by the 8th edition of TNM, using a national high-quality database,” wrote the researchers of the study. “By both presenting the models visually and testing their discriminative ability (C-index) and goodness of fit and complexity (BIC-test), we robustly compared the prognostic capabilities of 10 unique models.”

The TNM Staging System, developed by the American Joint Committee on Cancer and the Union for International Cancer Control, is the most widely used framework for classifying cancers worldwide.² It provides a standardized method to describe disease extent using three key components: the size and invasion depth of the primary tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). By combining these categories, physicians can assign an overall stage that guides prognosis, treatment planning, and comparisons across clinical studies. Moreover, its consistency and global adoption make TNM a cornerstone of oncological practice and research.

The researchers conducted a scoping literature review to identify novel prognostic models that integrate tumor deposits or tumor deposit counts into N-staging for CRC¹. Selected models were validated using patient data from the Swedish Colorectal Cancer Registry, encompassing 26,970 patients after applying exclusion criteria.

Outcomes assessed included overall survival, distant metastasis, and local recurrence. The prognostic performance of each model was compared with the traditional TNM N-staging system.

Out of 792 articles screened, 17 met the inclusion criteria, yielding 10 unique prognostic models in addition to the conventional TNM system. In the patient cohort, 3312 patients had tumor deposits. All identified models demonstrated superior prognostic performance compared with TNM N-staging. Two models stood out: one integrating lymph node count with tumor deposit count, and another ratio-based model considering tumor deposits, positive lymph nodes, and total extracted nodal structures.

While all models provided meaningful prognostic value for overall survival, distant metastasis, and local recurrence, the differences in predictive performance between the models were modest, suggesting that tumor deposit–based models enhance risk stratification but may require additional factors for further refinement.

However, the researchers acknowledged several limitations. Its retrospective design limited causal inference, and incomplete tumor deposit-count reporting across TNM editions may have affected model validation. Additionally, variability in histopathological assessment and extrapolation of models beyond their original populations could have reduced accuracy. Finally, lack of consensus on managing tumor deposit-positive patients and limited understanding of tumor deposit biology highlight the need for further research and validation in diverse cohorts.

Despite these limitations, the researchers believe the study demonstrates that incorporating tumor deposits into N-staging improves prognostic accuracy for colorectal cancer compared with the conventional TNM system.

“However, while TDs provide prognostic information for these patients, additional risk variables apart from T and M stage need to be included to further enhance the staging system,” wrote the researchers. “Further research is needed to establish a more comprehensive staging system and to determine the optimal treatment for high-risk patients.”

References

1. Lundström S, Agger E, Lydrup ML, et al. Rethinking TNM: Tumor deposit-based prognostic models may improve N-staging in colorectal cancer. Eur J Surg Oncol. 2025;51(11):110420. doi:10.1016/j.ejso.2025.110420

2. Cancer staging systems. American College of Surgeons. Accessed September 9, 2025. https://www.facs.org/quality-programs/cancer-programs/american-joint-committee-on-cancer/cancer-staging-systems/