Originally published as JCO Early Release 10.1200/JCO.2008.19.9273 on March 9 2009

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Patients With Initially Unresectable Colorectal Liver Metastases: Is There a Possibility of Cure?

René Adam, Dennis A. Wicherts, Robbert J. de Haas, Oriana Ciacio, Francis Lévi, Bernard Paule, Michel Ducreux, Daniel Azoulay, Henri Bismuth, Denis Castaing

From the AP-HP Hopital Paul Brousse, Centre Hepato-Biliaire and Department of Medical Oncology; L'Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 785; INSERM, Laboratoire ‘Rythmes biologiques et cancers’ Unité 776; Université Paris-Sud, Villejuif, France; and Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.

Corresponding author: Professor René Adam, MD, PhD, Assistance Publique Hôpitaux de Paris Hôpital Paul Brousse, Centre Hépato-Biliaire, 12 Ave Paul Vaillant Couturier, F-94804 Villejuif, France; e-mail: rene.adam{at}pbr.aphp.fr.

Purpose Although oncosurgical strategies have demonstrated increased survival in patients with unresectable colorectal liver metastases (CLM), their potential for cure is still questioned. The aim of this study was to evaluate long-term outcome after combining downsizing chemotherapy and rescue surgery and to define prognostic factors of cure.

Patients and Methods All patients with initially unresectable CLM who underwent rescue surgery and had a minimum follow-up of 5 years were included. Cure was defined as a disease-free interval 5 years from last hepatic or extrahepatic resection until last follow-up.

Results Mean age of 184 patients who underwent resection (April 1988 through July 2002) was 56.9 years. Patients had a mean number of 5.3 metastases (bilobar in 76%), associated to extrahepatic disease in 27%. Surgery was possible after one (74%) or more (26%) lines of chemotherapy. Five- and 10-year overall survival rates were 33% and 27%, respectively. Of 148 patients with a follow-up 5 years, 24 patients (16%) were considered cured (mean follow-up, 118.6 months), six (25%) of whom were considered cured after repeat resection of recurrence. Twelve "cured" patients (50%) had a disease-free interval more than 10 years. Cured patients more often had three or fewer metastases less than 30 mm (P = .03) responding to first-line chemotherapy (P = .05). Multivariate analysis identified maximum size of metastases less than 30 mm at diagnosis, number of metastases at hepatectomy three or fewer, and complete pathologic response as independent predictors of cure.

Conclusion Cure can be achieved overall in 16% of patients with initially unresectable CLM resected after downsizing chemotherapy. In addition to increased survival, this oncosurgical approach has real potential for disease eradication.

R.A. and D.A.W. contributed equally to this work.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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