The article by Donadon et al that appears in this issue of Gastrointestinal Cancer Research, (see “New Paradigm in the Management of Liver-Only Metastases From Colorectal Cancer” on page 20) is a comprehensive review of the data and supports the role of surgical intervention in selected patients with colon cancer metastases. The review covers a range of issues critical to improving our understanding of this approach, while also raising important questions that need to be addressed as we move forward.
First, it is becoming increasingly evident that patients treated at centers with the greatest experience and the greatest expertise have the best outcomes after hepatic resection. Clearly, a multidisciplinary approach linking medical oncology, surgical oncology, radiation oncology and interventional radiology is critical to optimize therapeutic benefit for patients who have potentially resectable disease. It is not clear to me that patients would be best served by being treated in smaller centers where these types of procedures are not routinely performed. As it has been shown in virtually every cancer surgery setting, decision-making and surgical expertise improve with experience. Therefore, strong recognition of this fact is needed and referral patterns must follow.
The second issue is one of patient selection. We are knowingly both undertreating and overtreating a great number of patients with metastatic colorectal cancer. While the previous standard of performing hepatic resections only for single isolated metastasis has been displaced, we do not yet know the maximum number of lesions, the upper limit of hepatectomy, or the anatomic lesion distribution that would still allow a benefit from the procedure. Resectability is very difficult to define for protocol purposes and even for the purpose of discussions in multidisciplinary board meetings. In many ways, resectability is in the eyes of the beholder, and different decisions may be made by different groups. Therefore, we should strive to define a set of standards so that outcomes can be objectively defined.
Chemotherapy has had a positive influence on the potential for surgical interventions. The increased response rates and acceptable toxicity profiles associated with new medicines have enabled more patients to become candidates for surgical resection. Balancing this progress, however, is increasing awareness of the potential negative consequences of chemotherapy on the liver and possibly other organs where resection is being performed. We have come to recognize that timing is important, and we may discover over time that, in fact, certain agents are less toxic than others when administered before resection.
While the debate continues regarding whether surgery or radiofrequency ablation (RFA) is the optimum therapeutic modality, I agree with the authors that surgery remains the gold standard whenever possible. RFA techniques appear best reserved for patients whose comorbidities preclude a surgical approach. Until data confirm that RFA provides better long-term outcomes, it should not be used as a standard approach in patients with resectable metastatic colon cancer.
Finally, I would add a note of caution. Our enthusiasm for surgical removal of metastases from colon cancer has potentially gone farther than merited by outcomes data. Reports of 60% positive 5- year outcomes, as in this paper, are in some ways disseminating a dangerous data set. Clearly, these high outcomes are a consequence of good patient selection, and probably do not adequately reflect modern patient selection based on the envelope having been pushed to the degree that it has. It is unfair to suggest to patients that they might have a 60% 5-year disease-free survival benefit from surgery, as this is probably an overestimation. When making risk-benefit decisions, we need to be as accurate as possible with patients so they understand both the shortterm and long-term consequences of their decisions. That being said, outcomes in appropriate patients for surgery are superior to those obtained with chemotherapy, and as procedure-related morbidity and mortality rates decrease, the value of these procedures increases. Hopefully, we will realize a 60% 5-year disease-free survival benefit in our patients using modern standards, but more data are needed to support this.