From the completion of neoadjuvant chemotherapy to surgery for colorectal cancer liver metastasis: What is the optimal timing?

Background Neoadjuvant chemotherapy (NAC) has been widely performed in the treatment of colorectal cancer liver metastasis (CRLM) patients, but the optimal timing of surgery after NAC is unclear. The aim of this study was to investigate the optimal timing of surgery. Methods From December 2010 to May 2018, 101 consecutive patients who received NAC followed by liver resection for CRLM were included in this study. The main outcome parameters were pathological response, progression-free survival (PFS), and overall survival (OS). The effect of time to surgery (TTS) on patient outcomes, defined as a high TTS and a low TTS according to an X-tile analysis, was investigated. To adjust for potential selection bias, propensity score matching at 1:2 was performed with two high TTS patients matched to one low TTS patient. Kaplan-Meier curves, logistic regression analyses, and Cox regression models were used for the data analysis. Results The optimal cut-off value for the TTS was 5 weeks by X-tile analysis. The patients in this study were divided into low (<= 5 weeks, n = 27) and high (>5 weeks, n = 74) TTS groups. Patients with a high TTS were more likely to have an unfavorable pathological response (75.7% vs 48.1%,P = .008). In multivariate analysis, a low TTS significantly predicted a better pathological response (OR = 3.397, 95% CI: 1.116-10.344,P = .031). Compared to patients with a high TTS, patients with a low TTS had significantly better PFS (P < .001, mPFS: 16 months vs 7 months) and better OS (P = .037, mOS: not reached vs 36 months). Multivariate analysis revealed that a TTS > 5 weeks was an independent predictor of decreased PFS (HR = 2.041, 95% CI: 1.152-3.616,P = .014) but not OS. After propensity matching, the patients with a low TTS had significantly better PFS (P < .001, mPFS: 18.2 months vs 10 months) and an equivalent OS (P = .115, mOS: not reached vs 41 months). Multivariate analysis revealed that a TTS > 5 weeks was an independent predictor of decreased PFS (HR = 3.031, 95% CI: 1.494-6.149,P = .002) but not OS. Conclusion The longer TTS after the completion of NAC may be disadvantageous for a favorable pathological response and long-term PFS. These results should be validated prospectively in a randomized trial.