Impact of sequential perioperative chemotherapy for high-risk colorectal liver metastases.

Background: The impact of perioperative chemotherapy, including neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC), given for resectable colorectal liver metastasis (CLM) remains unclear. This study evaluates the optimal strategy for managing high-risk CLM.

Methods: The subjects of this retrospective study were patients who underwent liver resection for initially resectable CLM between 2006 and 2021. High-risk status was defined by four or more metastases, a tumor size ≥ 5 cm, or the presence of resectable extrahepatic disease. Among 363 eligible patients, 293 received NAC and 70 underwent upfront surgery. Propensity score matching (PSM) created balanced groups of 70 each.

Results: Among the patients who received NAC, seven did not undergo resection because they had disease progression. Intention-to-treat analysis revealed significantly longer median progression-free survival (PFS) (1.1 vs. 0.6 years, p < 0.001) and overall survival (OS) (5.2 vs. 4.3 years, p = 0.044) in the NAC group. Matched analysis confirmed superior PFS (1.2 vs. 0.6 years, p = 0.004) and a favorable OS trend (5.4 vs. 4.3 years, p = 0.164). Completion of the perioperative sequence of NAC, surgery, and AC was associated with the most favorable outcomes.

Conclusion: Achieving a sequential strategy of NAC, surgery, and AC may improve the long-term survival of patients with high-risk CLM, supporting its potential as a standard treatment strategy.