The Role of Preoperative Chemotherapy in Patients with Resectable Colorectal Liver Metastases |
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Authors: | Stéphane Benoist MD PhD Bernard Nordlinger MD |
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Institution: | 1. Department of Digestive and Oncologic Surgery, AP-HP, H?pital Ambroise Paré Boulogne, Université Versailles Saint Quentin en Yvelines, 9 avenue Charles-de-Gaulle, Versailles, Cedex, France
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Abstract: | Background Liver metastases develop in 40–50% of patients with colorectal cancer and represent the major cause of death in this disease.
Surgical resection remains the only treatment procedure that can ensure long-term survival and provide cure when liver metastases
can be totally resected with clear margins, when the primary cancer is controlled, and when there is no nonresectable extrahepatic
disease. Five-year survival rate after surgical resection of colorectal metastases varies from 25% to 55%, but cancer relapse
is observed in most patients.
Aim To review the potential benefits and disadvantages of neoadjuvant chemotherapy administered before surgery to patients with
initially resectable metastases.
Results European Organization for Research and Treatment of Cancer (EORTC) study 40983 has shown that neoadjuvant chemotherapy could
reduce the risk of relapse by one-quarter, and allows to test the chemosensitivity of the cancer, to help to determine the
appropriateness of further treatments, and to observe progressive disease, which contraindicates immediate surgery. Neoadjuvant
chemotherapy can induce damage to the remnant liver. Oxaliplatin-based combination regimen is associated with increased risk
of vascular lesions, whereas irinotecan-containing regimens have been associated with increased risks of steatosis and steatohepatitis.
Analysis of EORTC study 40983 showed that administration of six cycles of neoadjuvant systemic chemotherapy with 5-fluorouracil,
leucovorin, and oxaliplatin (FOLFOX) was associated with moderate increase of the risk of reversible complications after surgery,
but mortality rate was below 1% and not increased. If patients are not overtreated, chemotherapy before surgery is well tolerated.
The integration of novel targeted agents in combination with cytotoxic drugs is a promising way to improve outcome in patients
with advanced colorectal cancer. Preliminary trials have shown that targeted agents combined with cytotoxic regimens can increase
tumor response rates. Another impact of preoperative chemotherapy is that metastases that respond to treatment may no longer
be visible on computed tomography (CT) scan or at surgery. Patients should be carefully monitored and receive surgery before
metastases disappear.
Conclusion Treatment of most patients with liver metastases—those with resectable metastases as well as those with initially unresectable
metastases—should start with chemotherapy. If drugs are well chosen and the duration of treatment is monitored with care during
multidisciplinary meetings, benefits largely outweigh potential disadvantages. |
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