What is the optimal number of neoadjuvant chemotherapy cycles for resectable colorectal liver oligometastases?

BACKGROUND: The optimal number of neoadjuvant chemotherapy (NAC) cycles for resectable colorectal liver oligometastases (CLOM) remains unclear. The aim of this study was to investigate the optimal number of NAC cycles. METHODS: One hundred twenty-nine consecutive patients were included in this study. X-tile analysis was implemented to investigate the optimal cut-off point for NAC cycles. Propensity score matching was performed to reduce selection bias. Kaplan-Meier curves and Cox risk regression models were used to analyse progression-free survival (PFS) and overall survival (OS). RESULTS: The optimal cut-off point for NAC cycles was 5. There were no significant differences in R0 resection, pathological response or postoperative complications between the groups with a low number of NAC cycles group (≤5 cycles, n=80) and high number of NAC cycles (>5 cycles, n=49). Patients with a high number of NAC cycles were more likely to have NAC toxicity than those with a low number of cycles (87.8% vs. 65.0%, P=0.004). Multivariate analysis revealed that >5 NAC cycles was an independent predictor of reduced PFS (HR =1.808, 95% CI: 1.205–2.712, P=0.004) and reduced OS (HR =1.723, 95% CI: 1.041–2.851, P=0.034). In the oxaliplatin-based regimen group, patients with a low number of NAC cycles had a better PFS (P<0.001, mPFS: 14.7 vs. 5.4 months) and better OS (P=0.018, mOS: 57.7 months vs. 41.0 months) than those with a high number of cycles. After 1:1 propensity matching (34 cases vs. 34 cases), multivariate analysis revealed that >5 NAC cycles was an independent predictor of reduced PFS (HR =2.265, 95% CI: 1.281–4.007, P=0.005) and reduced OS (HR =2.813, 95% CI: 1.359–5.822, P=0.005). In the oxaliplatin-based regimen group, patients with a low number of NAC cycles had better PFS (P<0.001, mPFS: 17.5 vs. 5.6 months) and better OS (P=0.008, mOS: 59.0 vs. 31.8 months) than those with a high number of cycles. CONCLUSIONS: Fewer than 5 NAC cycles was optimal for biologically resectable CLOM patients. Giving more than 5 NAC cycles was unnecessary because a higher number of NAC cycles has more unfavourable survival and higher NAC toxicities, while leading to similar R0 resection rates and pathological responses.