Anticipating the Clinical Use of Prognostic Gene Expression–Based Tests for Colon Cancer Stage II and III: Is Godot Finally Arriving?

Abstract

Purpose: According to current recommendations for adjuvant treatment, patients with colon cancer stage II are not routinely offered chemotherapy, unless considered to have a high risk of relapse based on specific clinicopathological parameters. Following these criteria, it is challenging to identify the subgroup of patients that will benefit the most from adjuvant treatment. Contrarily, patients with colon cancer stage III are routinely offered chemotherapy, but due to expected adverse effects and frailty, elderly patients are often excluded from standard protocols. Colon cancer is a disease of the elderly and accordingly, there is a large subgroup of patients for which guidelines for adjuvant treatment remain less clear. In these two clinical settings, improved risk stratification has great potential impact on patient care, anticipating that high-risk patients will benefit from chemotherapy. However, microsatellite instability is the only molecular prognostic marker recommended for clinical use.Experimental Design: In this perspective, we provide an updated view on the status and clinical potential of the many proposed prognostic gene expression-based tests for colon cancer stage II and III.Results: The main limitation for clinical implementation is lack of prospective validation. For patients with stage II, highly promising tests have been identified and clinical trials are ongoing. For elderly patients with stage III, the value of such tests has received less focus, but promising early results have been shown.Conclusion: Although awaiting results from prospective trials, improved risk assessment for patients with stage II and III is likely to be achieved in the foreseeable future.

LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor Colon Cancer Survival

“…A similar prognostic ability of LOXL2 was found for stage III patients. Although these patients are usually given adjuvant treatment, some groups (elderly and frail patients) do not always receive treatment (30). In this case, LOXL2 might help in clinical decisions for treating patients older than 75 years.…”

A nineteen gene‐based risk score classifier predicts prognosis of colorectal cancer patients

“…A recent study showed that more than a half of patients with advanced CRC experience clinical responses after systemic chemotherapy including targeted regimens (Midgley et al., 2009). Although patients with stage III CRC are routinely offered chemotherapy, elderly patients (≥75 years) are often excluded from the therapy, due to frailty coping with unfavourable adverse events (Sveen et al., 2013). A guideline is thereby needed for adjuvant treatment in the elderly patients with advanced CRC.…”

Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair–Proficient Stage II Colon Cancer

“…In particular, several gene expression-based prognostic tests are being evaluated and are at varying stages of development (12). Though some of these gene expression signatures have been validated in independent patient cohorts, they are not currently recommended for use in risk assessment and in the determination of adjuvant treatment by clinical guidelines due to the lack of prospective study data to validate their clinical utility (13, 14).…”