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Editorial |
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, Texas 77030
Correspondence: Address correspondence and reprint requests to: Jean-Nicolas Vauthey, MD; E-mail: jvauthey{at}mdanderson.org.
In this issue of Annals of Surgical Oncology, Masi et al.1 report on a group of 74 patients who presented with unresectable hepatic colorectal metastases and were treated before surgery with a fluoropyrimidine-based chemotherapy regimen that combined oxaliplatin and irinotecan (5-fluorouracil/folinic acid, oxaliplatin, and irinotecan; FOLFOXIRI). This regimen was associated with a high response rate (72%), and surgical resection was subsequently possible in 19 responders (26%). After a median follow-up of 34 months, survival was longer in patients who had a response to chemotherapy followed by resection compared with patients who had response without surgery (37 vs. 22 months).
Although the activity of the FOLFOXIRI regimen (response rate of 72%) seems to be higher than the rate reported with fluoropyrimidines combined either with irinotecan or oxaliplatin (response rates of 54% and 56%, respectively),2 the resectability rate of 26% reported by Masi et al. is similar to the previously reported rate, which ranged from 14% to 38%.3,4 Furthermore, the favorable results of Masi et al. should be balanced against the minimal benefit in disease-free survival, with only 3 of 74 patients disease free at the completion of the study.
Resection of hepatic colorectal metastases has gained acceptance on the basis of the finding that at 7 years after resection, disease-free and overall survival converge (even in patients never treated with chemotherapy) such that some patients are truly cured.5 In this context, the lack of durable disease-free survival reported by Masi et al. perhaps reflects the difficulty associated with complete resection of all residual disease in patients with initially unresectable hepatic colorectal metastases and emphasizes the need for defined strategies to select initially unresectable patients who are truly candidates for resection after chemotherapy.
Two important tenets in the assessment of resectability in initially unresectable patients not discussed by Masi et al. relate to the mapping and timing of surgery in an effort to optimize the goal of complete resection. The preferred approaches include one-stage or two-stage hepatectomy with or without portal vein embolization before second-stage surgery. Portal vein embolization is indicated to increase the volume of the anticipated liver remnant when the future liver remnant volume is 
20% of the standardized total liver volume.6 In addition, the so-called complete radiological response can be deceiving; therefore, anticipated resection should be mapped on the basis of the prechemotherapy imaging studies to encompass all metastatic lesions that were ever present. The experience with oxaliplatin-based preoperative chemotherapy for unresectable colorectal metastases suggests that the complete pathologic response rate is only 7%.7 For this reason, at M. D. Anderson Cancer Center, the initial imaging is reviewed by one of the hepatobiliary surgeons at the outset of chemotherapy to fully map the extent of the intrahepatic metastatic disease. High-quality imaging is routinely obtained, and a preliminary resection plan is made on the basis of relative bisegmental sparing. Whether positron emission tomography should be part of this algorithm remains unclear in the absence of a well-designed study comparing positron emission tomography and high-quality computed tomography reviewed by radiologists with expertise in hepatobiliary imaging. To optimize the timing for resection, repeat imaging should be obtained and reviewed during chemotherapy. Hepatic resection should be scheduled as soon as tumor downsizing makes the lesions resectable upon review by the hepatobiliary surgeon. The reasons are 2-fold. First, patients who undergo prolonged unnecessary preoperative chemotherapy are at risk of developing hepatic injury associated with chemotherapy (steatosis from irinotecan and sinusoidal injury from oxaliplatin).8,9 Second, with chemotherapy-induced steatosis, the sensitivity of intraoperative imaging and, thus, the accuracy of intraoperative mapping are decreased by the echogenic, injured hepatic parenchyma.
Progressive improvement in survival after resection of hepatic colorectal metastases has been reported in series from several specialized hepatobiliary centers, with postresection 5-year survival rates of 53% to 58%.10–12 Further progress is needed to enable the survival of patients with resected disease after downsizing chemotherapy for initially unresectable disease to achieve the survival of those who present with resectable disease. Fortunately, the field is rapidly evolving; recently approved molecular-targeted agents such as bevacizumab and cetuximab offer the prospect of higher partial and complete response rates. Further research should focus on evaluation of factors associated with poor outcome and the selection of patients on the basis of biological predictors of outcome, such as human telomerase reverse transcriptase, rather than the response to chemotherapy, which may be deceiving.13,14
Received for publication August 31, 2005. Accepted for publication September 7, 2005.
REFERENCES
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  G. Poston, R. Adam, and J.-N. Vauthey Downstaging or Downsizing: Time for a New Staging System in Advanced Colorectal Cancer? J. Clin. Oncol., June 20, 2006; 24(18): 2702 - 2706. [Full Text] [PDF]
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