Delaying surgery beyond six weeks after systemic therapy reduces postoperative morbidity without evidence of impaired oncologic outcomes in colorectal liver metastases

BACKGROUND: The optimal timing of resection for colorectal liver metastases (CRLM) after systemic therapy remains unclear. This study evaluated the impact of time-to-surgery (TTS) on postoperative morbidity and oncologic outcomes. METHODS: In this retrospective cohort (2018-2022) from a German high-volume hepatobiliary center, 159 patients underwent hepatic resection for CRLM following systemic therapy. Patients were stratified by TTS ≤ 41 versus ≥ 42 days. The primary endpoint was clinically meaningful postoperative morbidity (Comprehensive Complication Index ≥ 30). Secondary endpoints included liver-specific recurrence-free survival (RFS) and overall survival (OS). Multivariable regression, Cox proportional-hazards models, and prespecified subgroup analyses were performed. RESULTS: CCI ≥ 30 occurred in 48.7% of patients with shorter TTS versus 31.3% with longer TTS (P = 0.023). After multivariable adjustment, TTS ≥ 42 days was independently associated with lower odds of postoperative morbidity (OR 0.355; 95% CI 0.127-0.992; P = 0.048). In the subgroup of major hepatectomies, TTS ≥ 42 days demonstrated an even more pronounced protective effect (OR 0.069; 95% CI 0.006-0.778; P = 0.031). However, TTS ≥ 42 days was not independently associated with liver-specific RFS or OS. CONCLUSION: Delaying surgery to ≥ 6 weeks after neoadjuvant systemic therapy was associated with significantly reduced postoperative morbidity without evidence of impaired early oncologic outcomes among patients who ultimately underwent resection. These findings support consideration of a prolonged interval before complex hepatectomy while highlighting the need for prospective validation.