Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

J Natl Cancer Inst. 2017 Sep 1;109(9):djx015. doi: 10.1093/jnci/djx015.

Abstract

Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach.

Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat.

Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm.

Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Catheter Ablation / methods
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / surgery
  • Colorectal Neoplasms / therapy*
  • Disease-Free Survival
  • Fluorouracil / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery
  • Liver Neoplasms / therapy*
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol