Aggressive characteristics of tumor deposits in colorectal cancer highlight the need for staging refinement in patients with 0–3 metastatic lymph nodes

Abstract Accurate staging is essential for the optimal management of patients with colorectal cancer (CRC). The role of tumor deposits (TDs) in CRC staging has been contentious due to a lack of comprehensive understanding of their clinical and biological traits. In this retrospective study, we analyzed large data from 5718 CRC patients diagnosed between 2011 and 2022, ensuring rigorous data collection and long‐term follow‐up. Patients with positive TDs displayed aggressive clinical features. The risk factors for TDs varied among patients with different backgrounds of lymph node (LN) involvement, and the numbers of TDs and metastatic LNs showed a significantly positive correlation. TDs significantly impacted CRC prognosis, resulting in unfavorable outcomes irrespective of LN status. To delve into the biological characteristics of TDs, we performed transcriptome sequencing, immunohistochemistry, and Kaplan–Meier analyses on tissue samples from the additional CRC cohort and The Cancer Genome Atlas datasets. TDs exhibited aggressive biological phenotypes that were distinct from primary tumors and metastatic LNs, characterized by elevated signatures of epithelial‐mesenchymal transition, angiogenesis, and immune suppression. Cox proportional hazards analysis was then applied to reassess the appropriate role of TDs within the TNM staging system, revealing that the prognostic weightiness of TDs in CRC corresponded to N2a rather than N1 in patients with 0–3 LN metastases. Overall, our comprehensive analysis showed that TDs, with their aggressive clinical and biological characteristics, could optimize the staging of CRC, highlighting the need to refine their role within the TNM staging system.