Beyond N staging in colorectal cancer: Current approaches and future perspectives

Abstract

Traditionally, lymph node metastases (LNM) evaluation is essential to the staging of colon cancer patients according to the TNM (tumor–node–metastasis) system. However, in recent years evidence has accumulated regarding the role of emerging pathological features, which could significantly impact the prognosis of colorectal cancer patients. Lymph Node Ratio (LNR) and Log Odds of Positive Lymph Nodes (LODDS) have been shown to predict patients’ prognosis more accurately than traditional nodal staging and it has been suggested that their implementation in existing classification could help stratify further patients with overlapping TNM stage. Tumor deposits (TD) are currently factored within the N1c category of the TNM classification in the absence of lymph node metastases. However, studies have shown that presence of TDs can affect patients’ survival regardless of LNM. Moreover, evidence suggest that presence of TDs should not be evaluated as dichotomic but rather as a quantitative variable. Extranodal extension (ENE) has been shown to correlate with presence of other adverse prognostic features and to impact survival of colorectal cancer patients. In this review we will describe current staging systems and prognostic/predictive factors in colorectal cancer and elaborate on available evidence supporting the implementation of LNR/LODDS, TDs and ENE evaluation in existing classification to improve prognosis estimation and patient selection for adjuvant treatment.

TNMD system- A better staging in predicting prognosis of patients with stage III colon cancer

“…Upon microscopic observation of the pathological structure of both the RLN and TD, it was found that the TD possessed brous capsule and lacked any lymph node tissue. In contrast, the RLN was mainly composed of lymph node tissue (Arrichiello et al, 2022;Brouwer & Nagtegaal, 2021). Regional lymph node invasion, as the major metastasis pathway of colon cancer, played a decisive role in the postoperative staging of patients with colon cancer (Wang et al, 2023).…”

Tumour Extracellular Vesicles Induce Neutrophil Extracellular Traps To Promote Lymph Node Metastasis

“…Currently, the only relevant prognostic feature is the presence or absence of overt metastatic tumour cells within the LNs. However, this solely tumour centric system overlooks the role of immune and non-tumour compartment within the LNs 9 . This is critical, as no treatment strategy to date has reliably prevented the emergence of distant metastasis.…”

Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis

“…Currently, the only relevant prognostic feature is the presence or absence of overt metastatic tumour cells within the LNs. However, this solely tumour centric system overlooks the role of immune and non‐tumour compartments within the LNs (Arrichiello et al., 2022). Understanding this process before distant metastasis formation is critical, as no treatment strategy to date has reliably prevented the emergence of distant metastasis.…”