Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis

SIMPLE SUMMARY: The features of preoperative systemic anticancer therapy associated with best outcomes after resection of initially-irresectable liver metastases from colorectal cancer are yet to be identified. We harnessed data from a prospective international surgical database (LiverMetSurvey) to explore the duration and modalities of preoperative systemic anticancer therapy associated with longer overall survival in this clinical setting. Our study included 2793 patients having undergone liver surgery after preoperative systemic anticancer treatment for initially irresectable disease. We found that short (<7 or <13 cycles in 1st or 2nd line, respectively) duration was associated with longer survival outcomes, independently from other prognostic factors. Conversely, all the comparisons between different conventional active regimens displayed similar results. Our findings support the recommended onco-surgical approach of aiming at performing liver surgery as soon as technically feasible after response to preoperative systemic anticancer therapy in hepatic metastases from colorectal cancer, initially not amenable to surgery. The results of this study also suggest that, provided the systemic anticancer therapy regimen is active, the choice of the drugs used bears overall little if any impact on the outcomes. ABSTRACT: Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.