We determined the relative value of the metastatic colorectal cancer doubling time as a predictor of recurrence and survival after hepatectomy in comparison with other established predictors. Consecutive patients who underwent hepatic resection ( n = 144) for colorectal cancer liver metastases were studied retrospectively to identify factors that influence overall survival and recurrence in the remnant liver. Overall 5-year survival and nonrecurrence rates were 49.8% and 50.8%, respectively. By multivariate analysis, large liver tumors ( p = 0.038), p53 expression by the liver tumor (p = 0.011), and a short liver metastasis doubling time (< or = 45 days, p = 0.013) negatively affected survival; doubling times > 45 days (adjusted relative risk 0.06; p < 0.001) positively influenced disease-free survival. In patients with remnant liver recurrence, a short doubling time was associated with short disease-free intervals (7.3 +/- 6.2 months), multiple metastases (63.6%), and fewer attempts at repeat hepatectomy (22.7%). The doubling time determines tumor size and reflects the patient's immune and nutritional status. A short doubling time is the most reliable risk factor for multiple metastases, early recurrence, and poor prognosis. Further studies with a larger number of patients are needed to confirm this conclusion.
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