Timing of additional neoadjuvant chemotherapy in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and total mesorectal excision.

Background: In locally advanced rectal cancer (LARC), the optimal sequence of neoadjuvant chemotherapy in relation to neoadjuvant chemoradiotherapy and before total mesorectal excision is unknown.

Methods: A total of 426 LARC patients, treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision, between January 2010 and December 2018, were studied retrospectively. Patients were divided into induction and consolidation chemotherapy groups. Overall, disease-free, locoregional relapse-free, and distant metastasis-free survival rates for the 2 groups were compared. Multivariate analysis hazard ratios (HR) with 95% confidence intervals (CI) to identify survival predictors.

Results: Median follow-up was 37 (range, 7-162) months. The 3-year overall, disease-free, locoregional relapse-free, and distant metastasis-free survival rates were 93.8%, 71.6%, 93.5%, and 74.4%, respectively. For those receiving either induction or consolidation chemotherapy, 3-year disease-free survival rates were 82.5% and 67.7%, respectively (P = 0.021), distant metastasis-free rates were 85.4% and 70.8%, respectively (P = 0.024), and both overall and locoregional relapse-free survival rates did not differ significantly. Absence of neural invasion was an independent predictor of disease-free (HR = 0.49, 95% CI 0.25-0.97, P = 0.04) and distant metastasis-free (HR = 0.49, 95% CI 0.25-0.98, P = 0.04) survival. Both ypTN stage III (vs.0-II) and consolidation (vs. induction) chemotherapy were independent predictors of disease relapse (HR = 1.95, 95% CI 1.47-2.58, P < 0.001; HR = 1.68, 95% CI 1.01-2.79, P = 0.046; respectively) and distant metastasis (HR = 2.04, 95% CI 1.51-2.76, P < 0.001; HR = 1.75, 95% CI 1.03-2.99, P = 0.04; respectively).

Conclusions: LARC patients receiving neoadjuvant chemoradiotherapy and total mesorectal excision had better disease-free and distant metastasis-free survival, with induction rather than consolidation neoadjuvant chemotherapy.