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Complete Pathologic Response After Preoperative Chemotherapy for Colorectal Liver Metastases: Myth or Reality?

René Adam, Dennis A. Wicherts, Robbert J. de Haas, Thomas Aloia, Francis Lévi, Bernard Paule, Catherine Guettier, Francis Kunstlinger, Valérie Delvart, Daniel Azoulay, Denis Castaing

From the Assistance Publique–Hoptaux de Paris Hôpital Paul Brousse, Centre Hépato-Biliaire; Asistance Publique–Hoptaux de Paris Hôpital Paul Brousse, Department of Medical Oncology; Assistance Publique–Hoptaux de Paris Hôpital Paul Brousse, Department of Pathology; Inserm; Inserm, Laboratoire ‘Rythmes Biologiques et Cancers’; Université Paris-Sud, Villejuif, France; and the Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands

Corresponding author: Professor René Adam, MD, PhD, AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, 12 Avenue Paul Vaillant Couturier, F-94804 Villejuif, France; e-mail: rene.adam{at}pbr.aphp.fr

Purpose: Complete clinical response (CCR) of colorectal liver metastases (CLM) following chemotherapy is of limited predictive value for complete pathologic response (CPR) and cure of the disease. The objective of this study was to determine predictive factors of CPR as well as its impact on survival.

Patients and Methods: From January 1985 to July 2006, 767 consecutive patients with CLM underwent liver resection after systemic chemotherapy. Patients with CPR were compared with patients without CPR.

Results: Twenty-nine of 767 (4%) patients had CPR, and none of these 29 patients had CCR. Patients with CPR (mean age, 54 years) had a mean number of 3.3 metastases at diagnosis (mean size, 29.3 mm). Objective response and stable disease were observed in 79% and 21% of cases, respectively. Postoperative mortality rate was 0%. After a median follow-up of 52.2 months (range, 1.1 to 193.0 months), overall 5-year survival was 76% for patients with CPR compared with 45% for patients without CPR (P = .004). Independent predictive factors for CPR were: age 60 years, size of metastases 3 cm at diagnosis, carcinoembryonic antigen (CEA) level at diagnosis 30 ng/mL, and objective response following chemotherapy. The probability of CPR ranged from 0.2% when all factors were absent to 30.9% when all were present.

Conclusion: CPR was observed in 4% of patients with CLM treated with preoperative chemotherapy. However, CPR may occur in almost one-third of objective responders age 60 years with metastases 3 cm and low CEA values. CPR is associated with uncommon high survival rates.

Presented at the 2007 Annual Meeting of the American Society of Clinical Oncology, June 1-5, Chicago, IL.

Both 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.