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.