Timing of Multimodality Therapy for Resectable Synchronous Colorectal Liver Metastases

Abstract

The optimal timing of chemotherapy relative to resection of synchronous colorectal liver metastases (SCRLM) is not known. The objective of this retrospective multi-institutional study was to assess the influence of chemotherapy administered before and after hepatic resection on long-term outcomes among patients with initially resectable SCRLM treated from 1995 to 2005. Clinicopathologic data, treatments, and long-term outcomes from patients with initially resectable SCRLM who underwent partial hepatectomy at three hepatobiliary centers were reviewed. Four hundred ninety-nine consecutive patients underwent resection; 297 (59.5%) and 264 (52.9%) were treated with chemotherapy before and after resection. Chemotherapy strategies included pre-hepatectomy alone (n = 148, 24.7%), post-hepatectomy alone (n = 115, 23.0%), perioperative (n = 149, 29.0%), and no chemotherapy (n = 87, 17.4%). Male gender (p = 0.0029, HR = 1.41 [1.12–1.77]), node-positive primary tumor (p = 0.0046, HR = 1.40 [1.11–1.77]), four or more SCRLM (p = 0.0005, HR = 1.65 [1.24–2.18]), and post-hepatectomy chemotherapy treatment for 6 months or longer (p = 0.039, HR = 0.75 [0.57–0.99]) were associated with recurrence-free survival after discovery of SCRLM. Carcinoembryonic antigen >200 ng/ml (p = 0.0003, HR = 2.33 [1.48–3.69]), extrahepatic metastatic disease (p = 0.0025, HR = 2.34 [1.35–4.05]), four or more SCRLM (p = 0.033, HR = 1.43 [1.03–2.00]), and post-hepatectomy chemotherapy treatment for 2 months or longer (p < 0.0001, HR = 0.59 [0.45–0.76]) were associated with overall survival. Pre-hepatectomy chemotherapy was not associated with recurrence-free or overall survival. Patients treated with perioperative chemotherapy had similar outcomes as patients treated with post-hepatectomy chemotherapy only. We conclude that chemotherapy administered after but not before resection of SCRLM was associated with improved recurrence-free and overall survival. However, prospective randomized trials are needed to determine the optimal timing of chemotherapy.