Tumour deposits are associated with increased metastatic risk in colorectal cancer: a population‐based analysis of metastatic patterns and burden

AIMS: Lymph node metastases (LNM) are traditionally regarded as the principal gateway for distant metastases in colorectal cancer (CRC), forming the foundation of TNM staging. Tumour deposits (TD) have emerged as a strong prognostic factor and potential alternative gateway for CRC spread. This study aimed to assess whether TD were associated with the risk of distant metastases and to characterize metastatic patterns and burden. METHODS AND RESULTS: A retrospective, population-based study included 3505 CRC patients without distant metastases at diagnosis, using data from the Netherlands Cancer Registry for the first half of 2015. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for metastatic risk. Metastatic patterns were summarized descriptively using pattern-to-patient ratios. Metastatic burden was categorized by the number of involved sites (1, 2, 3 or ≥4) and evaluated using the linear-by-linear association test. Of the 3505 patients, 2268 were N0, 934 were LNM+ and 303 were LNM + TD+. TD were independently associated with an increased risk of distant metastases (HR = 1.34, 95% CI: 1.03-1.74). Among patients who developed distant metastases, pattern-to-patient ratios were 0.30, 0.34 and 0.39 in the N0, LNM+ and LNM + TD+ groups, respectively, but were not formally compared because of their dependence on sample size. The distribution of metastatic burden differed across the three groups (P for trend = 0.017). The proportion with ≥4 involved sites was descriptively highest in the LNM + TD+ group (18.0% vs. 11.0% in LNM+ and 9.2% in N0). CONCLUSIONS: TD are independently associated with an increased risk of distant metastases in CRC. This finding supports consideration of TD in future risk stratification strategies and warrant further investigation into whether TD mark a distinct metastatic phenotype rather than merely reflecting locoregional disease progression.