Type of response to conversion chemotherapy strongly impacts survival after hepatectomy for initially unresectable colorectal liver metastases

Background: Hepatectomy for initially unresectable colorectal liver metastases (IU-CLM) is considered at high risk due to the extensive preoperative chemotherapy (CHT) and complex surgical procedures required, and its results are questioned due to frequent and early post-operative recurrence. We aim to compare patients with initially resectable CLM (IR-CLM) and IU-CLM and identify prognostic factors among IU-CLM patients. Methods: A total of 81 patients with IU-CLM, undergoing hepatectomy following conversion CHT, were compared to 526 IR-CLM patients. Predictors of overall (OS) and disease-free survival (DFS) were identified for IU-CLM patients. Results: Patients resected for IU-CLM, compared to IR-CLM, had more and larger CLM and more frequently underwent prolonged CHT and major/extended hepatectomy (P < 0.001 for all comparisons). Such characteristics paralleled higher rates of overall and major (Clavien-Dindo ≥3) complications, longer median post-operative length of stay and lower 5-year survival rates (P < 0.001 for all comparisons) among IU-CLM patients compared to IR-CLM, with similar mortality (1.2% and nil for IU-CLM and IR-CLM, respectively). Among IU-CLM patients, 62 with partial response to CHT (versus tumour stability according to the Response Evaluation Criteria in Solid Tumors criteria) had better DFS (hazard ratio 2.76, P = 0.001) and OS (hazard ratio 2.83, P = 0.002), and their 5-year survival rates (DFS 19.8%, OS 46.7%) approached those of IR-CLM patients (DFS 31%, OS 59%, P > 0.05 for both comparisons). Conclusion: Resection of IU-CLM has acceptable perioperative results. Tumour responsiveness to conversion CHT improves IU-CLM patient selection for hepatectomy.