Expanded criteria for surgery for liver metastases: thoughtful science or diamond mining?

The controversial topic of major liver resection with curative intent in the presence of what has traditionally been categorized as incurable nodal disease is explored in the article in this issue of the Journal of Clinical Oncology by Adam et al. The authors present us their successes—their diamonds. The patients described in this article were treated at a large-volume hospital, by an experienced team of surgeons, medical oncologists, and radiologists with far more experience than most in the treatment of hepatic metastases from colorectal cancer. For reference, the presence of portal nodal metastases identified in the preoperative evaluation of the extent of the metastatic disease has usually been used as a contraindication to resection. Nodal metastases beyond that area have such a consistently poor prognosis that the finding of a single node in a basin beyond the porta hepatis would exclude a patient from operation. This is even true in patients with nonmetastatic, primary liver tumors such as hepatocellular or cholangiocarcinoma. In fact, this and other articles have documented the dismal outcome when nodal metastases beyond the porta hepatis in combination with liver metastases is identified either pre-, intra-, or postoperatively. However, there is still controversy regarding whether porta hepatis nodes that appear synchronously (on preoperative evaluation or on intraoperative inspection) with the liver metastases are also incurable with aggressive combined-modality therapy. A key element in supporting lymph node dissection would be the documentation of specific lymph node failure in this group compared with a group that underwent lymph node dissection. It is so exceedingly rare for lymph node disease to be life-limiting, that this alone might not be a powerful argument to support the use of radical lymph node dissection. Even the most aggressive teams treating metastatic colorectal cancer to the liver have been sanguine enough to avoid this recommendation for the purpose of anything but documentation of disease extent. Surgical teams performing synchronous porta hepatic nodal dissections have carefully limited their reported conclusions to documentation of poor prognosis, treatment planning, and stratification in clinical trials, but nothing as far reaching as improved survival. In examining the Patients and Methods section in the study by Adam et al, one can see that the population of patients eligible for this surgery is small. Selection factors that defy specific categorization have been applied before and even during the selection of the radical lymph node dissection/hepatic resection (RLND/HR) patients. There were 763 patients in 14 years, with 47 patients (6%) undergoing RLND/HR. Twenty-six had disease beyond the porta hepatic, thus reducing the total number who would potentially benefit to a very small number. Only 21 patients (2.8%) had disease limited to the porta hepatis. Furthermore, if identified preoperatively, patients had to have responded to chemotherapy to be further treated with RLND/HR. When identified intraoperatively by palpation of an abnormal node, RLND was performed after a biopsy documented metastatic nodal disease. A selection bias is clearly demonstrated by the relative survival difference between patients who were preoperative responders (35% 5-year OS and 43-month median survival) compared with those who were identified intraoperatively and were therefore “response unknown” (10% 5-year OS and 27-month median survival). The fact that these two clinical settings are not statistically significantly different may be due to other selection and prognostic factors not collected or analyzed that are meaningful contributors to the outcome. Finally, given that all patients received chemotherapy, it is paradoxical that the preoperatively, radiographically imaged nodal disease patients do better than those with subclinical nodal disease detected intraoperatively. The greatest confounding factor in drawing conclusions is the extent of chemotherapy before and after RLND/HR in each patient. Three explanations might be offered. First, patients treated before surgical evaluation and experiencing disease progression in the nodal areas were never sent to the surgical team, thus improving the outcome by selection of patients with better biology and excluding those who would not benefit from additional postoperative chemotherapy. Second, the active modality in the treatment of the liver metastases was not the surgery but rather the chemotherapy; that is, in the absence of effective chemotherapy, surgery has no value. A third explanation is that the combined debulking by surgery and chemotherapy is the most active combination. These three explanations are controversial and are not supported by the literature. Unfortunately, although the one most valuable piece of information would be the ability to dissect the predictors of success, this does not seem possible. It is prudent to consider that the time span of patient accrual was 14 years, just fewer than two patients per year. During that time, the chemotherapeutic and biologic treatment of metastatic colorectal cancer underwent nothing short of a revolution, and surgical approaches were refined and expanded. It is extremely difficult to be confident in concluding that either the nodal dissection or hepatic resection were the key—or even a contributory factor—in the survival of these patients. Furthermore, RLND/HR was performed at the first, second, and even third attempt at clearing the liver of metastatic disease. We must all recognize the overwhelming contribution of individual patientdisease-treatment interaction. It is naive to think we have the ability to categorize these patients on standard parameters, such as age, tumor JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 26 NUMBER 22 AUGUST 1 2008