QS121 - Neoadjuvant Chemotherapy in Non-Metastatic T4 Colon Cancers: A Systematic Review and Meta-Analysis

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Purpose/Background: Non-metastatic T4 colon cancer, characterized by invasion into adjacent structures or organs, represents a significant therapeutic challenge. The standard treatment for these patients involves surgical resection followed by adjuvant chemotherapy (AC). However, emerging evidence suggests that neoadjuvant chemotherapy (NAC) may provide additional benefits by downstaging tumors, increasing the likelihood of R0 resection, and improving overall survival (OS). Despite promising findings, NAC has not been widely adopted, and the potential survival benefits remain to be fully explored. We reviewed the current data on oncologic outcomes and perioperative complications of NAC, when compared to AC, in patients with non-metastatic T4 colon cancer.

Methods/Interventions: A systematic search of studies published from 2018 to 2023 was conducted in major databases including MEDLINE, Embase, PubMed, Cochrane Library, and Web of Science. Only observational studies and cohort studies comparing NAC to AC in adult patients with non-metastatic T4 colon cancer were included. To date, only a limited number of randomized trials have attempted to show the benefits of NAC, specific to T4 colon cancers. Studies were selected based on predefined inclusion criteria, focusing on overall survival, R0 resection rates, and perioperative morbidity as key outcomes. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist for cohort studies and reviewed by two independent reviewers. The pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated for each outcome using a random-effects model to account for heterogeneity across studies, and heterogeneity was evaluated using the I² statistic.

Results/Outcomes: Five studies met the inclusion criteria, with a total of 131 to over 100,000 participants per study. The meta-analysis found that NAC was associated with improved 5-year OS compared to AC (OR = 0.59, 95% CI: 0.35–1.00, p = 0.05), suggesting a 41% reduction in the odds of death at 5 years for NAC patients. However, moderate heterogeneity was observed (I² = 75%). NAC was also linked to improved R0 resection rates in most studies, but the pooled OR (1.57, 95% CI: 0.34–7.22, p = 0.56) indicated no significant overall difference, with substantial heterogeneity (I² = 91%). Perioperative morbidity, including anastomotic leaks and infections, did not show significant differences between NAC and AC groups (OR = 0.86, 95% CI: 0.10–7.29, p = 0.89), but heterogeneity was extremely high (I² = 99%).

Conclusion/Discussion: This meta-analysis provides evidence that NAC may improve OS in patients with non-metastatic T4 colon cancer, although no significant difference was observed in R0 resection rates, or perioperative morbidity. The high heterogeneity across studies highlights that multiple variables may impact the overall analysis, such as variability of patient characteristics, differences in NAC protocols, and non-standardized surgical approaches. Standardizing chemotherapy protocols and improving perioperative care may also help optimize outcomes for these high-risk patients.