Long-Term Outcome With Combined-Modality vs Systemic Treatment for Unresectable Colorectal Liver Metastases


Key Points

  • Among patients with colorectal liver metastases, combined-modality therapy was associated with improved overall survival vs systemic therapy alone, at median follow-up of 9.7 years.
  • Overall survival was 35.9% vs 8.9% at 8 years.

The long-term follow-up of a phase II trial reported by Ruers et al in the Journal of the National Cancer Institute showed a 42% reduced risk of death among patients with colorectal liver metastases receiving aggressive local treatment plus systemic therapy vs systemic therapy alone.

Study Details

Beginning in April 2002, patients were recruited from 22 sites in Europe; the trial was prematurely closed for poor accrual in June 2007, due to physicians’ preferences in treatment modalities. Overall, 119 patients with up to 9 unresectable colorectal liver metastases (median of 4–5) and no extrahepatic disease received systemic treatment plus radiofrequency ablation with or without resection (n = 60) or systemic treatment alone (n = 59). Between April 2002 and October 2005, systemic treatment consisted of fluorouracil, leucovorin, and oxaliplatin (FOLFOX4), with bevacizumab (5 mg/kg every 2 weeks) being added after 2005.

Major Results

Prior reports from the study showed that the primary endpoint of 30-month overall survival > 38% in the combined-modality group was met, with the group having overall survival of 61.7% at this time point. Primary analysis at a median follow-up of 4.4 years showed that median progression-free survival was 16.8 months in the combined-modality group vs 9.9 months in the systemic treatment group (P = .025).

In the current report, at a median follow-up of 9.7 years, 92 of 119 patients (77.3%) had died, including 39 of 60 (65.0%) in the combined-modality group vs 53 of 59 (89.9%) in the systemic treatment group (hazard ratio = 0.58, P = .01). Among patients who died, death was due to progressive disease in 35 of 39 in the combined-modality group and in 49 of 53 in the systemic treatment group. Overall survival rates were 56.9% vs 55.2% at 3 years, 43.1% vs 30.3% at 5 years, and 35.9% vs 8.9% at 8 years, respectively. Median overall survival was 45.6 months vs 40.5 months.

The investigators concluded: “This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong [overall survival] in patients with unresectable colorectal liver metastases.”

The trial was supported by Cancer Research UK, Arbeitsgruppe Lebermetastasen und tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie, Dutch Cancer Foundation, U.S. National Cancer Institute, European Organisation for Research and Treatment of Cancer Charitable Trust, and Sanofi-Aventis.

Theo Ruers, MD, PhD, of the Netherlands Cancer Institute, is the corresponding author of the Journal of the National Cancer Institute article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.