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The following is a summary of “Neoadjuvant Chemotherapy for Colon Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials,” published in the June 2025 issue of the European Journal of Cancer by Noronha et al.

Neoadjuvant chemotherapy (NAC) has emerged as a promising strategy to improve clinical outcomes in patients with non-metastatic colon cancer, serving as an alternative to the traditional approach of upfront surgery. However, its role remains a subject of debate. To address this uncertainty, researchers conducted a systematic review and meta-analysis of RCTs to evaluate the survival benefit and feasibility of NAC in patients with high-risk stage II and stage III colon cancer.

A comprehensive literature search was performed using PubMed, Embase, and the Cochrane Library to identify relevant clinical trials. Statistical analyses were conducted using both random-effects and fixed-effects models within Review Manager software version 5.4, and heterogeneity was assessed using the I² statistic.

The final analysis included data from 1,248 patients across four randomized clinical trials. Results demonstrated that patients who received NAC experienced a significant 38% reduction in the risk of death compared to those undergoing upfront surgery ([HR] 0.62; 95% [CI] 0.41–0.92; I²  = 0%). Additionally, NAC was associated with a 21% reduction in the risk of disease recurrence (HR 0.79; 95% CI 0.65–0.96; I²  = 0%). Surgical outcomes also favored NAC, with a significantly higher likelihood of achieving an R0 resection, reflecting an 80% increase in odds compared to the upfront surgery group ([OR] 1.80; 95% CI 1.24–2.61; I²  = 0%).

Regarding pathological responses, a pathological response (pCR) was achieved in 5.9% of patients, while a major pathological response was observed in 36.2%. Subgroup analyses indicated that patients with proficient mismatch repair tumors achieved slightly higher pCR rates (6.3%) and demonstrated a consistent reduction in recurrence risk compared to the overall cohort. Importantly, the addition of NAC did not result in a significant increase in treatment-related toxicity.

In conclusion, this systematic review and meta-analysis support the feasibility and clinical benefit of neoadjuvant chemotherapy for patients with high-risk stage II and stage III colon cancer. NAC not only improves survival and disease control but also enhances surgical outcomes without adding substantial toxicity. These findings suggest that NAC should be considered a viable treatment option in appropriately selected patients, although further studies are warranted to refine patient selection and optimize treatment protocols.

Source: ejcancer.com/article/S0959-8049(25)00257-6/abstract