Blood vessel invasion in colorectal cancer--an alternative to TNM staging?

Since the publication of the National Cancer Institute (NCI) consensus conference supporting the role of adjuvant therapy for T3 and/or N1–2 rectal cancer and a number of randomized trials revealing the advantage of adjuvant chemotherapy for N1–2 colon cancer, these therapies have become the standard of care. To better select patients for these therapies, a variety of clinical, pathologic, and molecular prognostic factors have been examined. The goal of these studies is to determine if these factors are independent prognostic factors and, therefore, can be used to identify subsets of patients within a given stage who are more likely or less likely to need adjuvant therapy. Since the initial report by Brown and Warren in 1938 demonstrating an increase in visceral metastasis in patients with rectal cancer with vascular invasion, a number of investigators have examined the influence of vascular invasion by tumor in colorectal cancer. There are two types of vascular invasion: blood vessel and lymphatic vessel invasion. One would predict the presence of vascular invasion to be associated with an increased incidence of lymph node and distant metastasis and with a corresponding decrease in survival; this is not a consistent finding, however. Differences in the definition of vascular invasion, the methods of detection, and perhaps the metastatic potential of the cells once they have gained access to blood and lymphatic vessels may explain, in part, some of the variations observed. The objective of the interesting study by Sternberg and colleagues published in this issue of the Annals of Surgical Oncology was to determine whether the number of positive nodes in patients with node-positive colorectal cancer was predictive of survival. The 171 patients were retrospectively staged by four methods: TNM stage; Astler-Coller stage; GITSG stage; and the presence or absence of venous invasion (blood vessel invasion [BVI]). In the TNM and GITSG staging systems, the N stage is based on the presence or absence, as well as the number, of positive nodes. In contrast, the Astler-Coller staging system accounts for the presence or absence of positive nodes but not for the number of positive nodes. Survival curves for each staging method were compared. Of the four staging methods, the Astler-Coller stage and the presence or absence of BVI had the most significant correlation with survival. There was no significant correlation between the number of positive nodes and survival. The authors conclude that in the subset of patients with positive nodes, the number of positive nodes is not as predictive of survival as is T stage or BVI. They recommend BVI as the method of choice for predicting prognosis in node-positive patients. Do the data support this conclusion, and was the study designed adequately to answer this question? First, only 16% of patients had BVI-positive tumors, which limits the statistical power of the study. Furthermore, a multivariate analysis was not performed. This type of analysis is required to determine if a variable is an independent prognostic factor. Horn and colleagues found that BVI was an independent prognostic factor for distant metastasis but not for survival.1 By multivariate analysis, Chapuis and colleagues found BVI to be an independent prognostic factor for survival,2 but this was not confirmed by Wiggers et al.3 or Minsky et al.4 Also, given that most of the literature supports the finding that the TNM stage is an independent prognostic factor and this series does not report this, the results need to be interpreted with caution. The second issue is that patients with both colon and rectal cancer are included. These sites have different survival rates. In addition, adjuvant therapy improves Received October 15, 1998; accepted October 16, 1998. From the Departments of Radiation Oncology (BDM) and Surgery (AMC), Memorial Sloan-Kettering Cancer Center, New York, New York. Address correspondence to: Bruce D. Minsky, MD, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021; Fax: 212-794-3198. Annals of Surgical Oncology, 6(2):129–130 Published by Lippincott Williams & Wilkins © 1999 The Society of Surgical Oncology, Inc.