Evaluating the oncological safety of neoadjuvant chemotherapy in locally advanced colon carcinoma: a systematic review and meta-analysis of randomised clinical trials and propensity-matched studies

Abstract

Abstract Purpose Use of neoadjuvant chemotherapy (NAC) for locally advanced colon cancer (LACC) remains controversial. An integrated analysis of data from high-quality studies may inform the long-term safety of NAC for this cohort. Our aim was to perform a systematic review and meta-analysis of randomised clinical trials (RCTs) and propensity-matched studies to assess the oncological safety of NAC in patients with LACC. Methods A systematic review was performed as per preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Survival was expressed as hazard ratios using time-to-effect generic inverse variance methodology, while surgical outcomes were expressed as odds ratios (ORs) using the Mantel-Haenszel method. Data analysis was performed using Review Manager version 5.4. Results Eight studies (4 RCTs and 4 retrospective studies) including 31,047 patients with LACC were included. Mean age was 61.0 years (range: 19–93 years) and mean follow-up was 47.6 months (range: 2–133 months). Of those receiving NAC, 4.6% achieved a pathological complete response and 90.6% achieved R0 resection (versus 85.9%, P < 0.001). At 3 years, patients receiving NAC had improved disease-free survival (DFS) (OR: 1.28, 95% confidence interval (CI): 1.02–1.60, P = 0.030) and overall survival (OS) (OR: 1.76, 95% CI: 1.10–2.81, P = 0.020). When using time-to-effect modelling, a non-significant difference was observed for DFS (HR: 0.79, 95% CI: 0.57–1.09, P = 0.150) while a significant difference in favour of NAC was observed for OS (HR: 0.75, 95% CI: 0.58–0.98, P = 0.030). Conclusion This study highlights the oncological safety of NAC for patients being treated with curative intent for LACC using RCT and propensity-matched studies only. These results refute current management guidelines which do not advocate for NAC to improve surgical and oncological outcomes in patients with LACC. Trial registration International Prospective Register of Systematic Review (PROSPERO) registration: CRD4202341723.