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The role of preoperative chemotherapy in patients with resectable colorectal liver metastases
Annals of Surgical Oncology, 06/29/09

Benoist S et al. - In a review of the potential benefits and disadvantages of neoadjuvant chemotherapy administered before surgery to pts with initially resectable metastases, it was found that treatment of most pts with liver metastases—those with resectable metastases and those with initially unresectable metastases—should start with chemotherapy. If drugs are well chosen and duration of treatment is monitored with care during multidisciplinary meetings, benefits outweigh potential disadvantages.

Methods

Liver metastases develop in 40–50% of pts with colorectal cancer (CRC) and represent the major cause of death.
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.
5-yr survival rate after surgical resection of colorectal metastases varies from 25% to 55%, but cancer relapse is observed in most pts.
This study reviewed the potential benefits and disadvantages of neoadjuvant chemotherapy administered before surgery to pts with initially resectable metastases.

Results

EORTC study 40983 has shown that neoadjuvant chemotherapy could reduce the risk of relapse by one-quarter, and allows testing of chemosensitivity of the cancer, to help determine appropriateness of further treatments, and observe progressive disease, which contraindicates immediate surgery.
Neoadjuvant chemotherapy can induce damage to the remnant liver.
Oxaliplatin-based combination regimens are associated with increased risk of vascular lesions, whereas irinotecan-containing regimens have been associated with increased risk of steatosis and steatohepatitis.
Analysis of EORTC study 40983 showed that administration of 6 cycles of neoadjuvant systemic chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was associated with moderate increase of risk of reversible complications after surgery, but mortality rate was <1% and not increased.
If pts are not overtreated, chemotherapy before surgery is well tolerated.
Integration of novel targeted agents in combination with cytotoxic drugs is a promising way to improve outcome in pts with advanced CRC.
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 scan or at surgery.
Pts should be carefully monitored and receive surgery before metastases disappear.