Simultaneous versus staged resection for conversion surgery in initially unresectable colorectal liver metastases: a multicenter prospective cohort study

Background: For patients with initially unresectable colorectal liver metastases (IU-CRLM) who achieve resectability through conversion therapy, the choice between simultaneous and staged resection remains controversial. This pioneering prospective cohort study directly compares these approaches, offering critical insights into their safety and oncologic efficacy. Materials and Methods: This multicenter prospective cohort study, conducted across three centers from January 2009 to June 2022 (median follow-up 49.8 months), enrolled 366 patients with IU-CRLM who achieved resectability after conversion therapy. Patients underwent either simultaneous or staged resection of primary and metastatic lesions. Primary outcomes included postoperative complications (Clavien-Dindo ≥II and ≥III), relapse-free survival (RFS), liver-specific RFS, and overall survival (OS). Results: Among 366 patients (229 staged, 137 simultaneous), staged resection showed lower overall complications (35.8% vs. 48.9%, P = 0.014) and major complications (14.8% vs. 24.1%, P = 0.027). Staged resection improved RFS (HR = 0.780, 95% CI 0.623–0.977, P = 0.030) and liver-specific RFS (HR = 0.737, 95% CI 0.584–0.932, P = 0.011), with no significant OS difference (HR = 0.811, 95% CI 0.594–1.108, P = 0.188). Multivariable analysis confirmed staged resection’s independent benefits for RFS (HR = 0.587, P = 0.001), liver-specific RFS (HR = 0.522, P<0.001), and OS (HR = 0.529, P = 0.003). Conclusion: This study provides compelling evidence that staged resection is the safer and more effective surgical strategy for IU-CRLM patients achieving resectability through conversion therapy. With significantly lower complication rates and improved survival outcomes, these findings strongly support the adoption of staged resection in clinical practice. Randomized controlled trials are essential to confirm these results and refine treatment guidelines.