Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us.

A substantial number of clinical trials using antiangiogenic therapies are ongoing worldwide. How to achieve the maximum benefit from these therapies and how to monitor patient response are of paramount concern to investigators. There are currently no markers of the net angiogenic activity of a tumor available to aid investigators in the design of antiangiogenic treatment schemes. It stands to reason that quantification of various aspects of tumor vasculature might provide an indication of angiogenic activity. One often-quantified aspect of tumor vasculature is microvessel density. Studies over the last decade have demonstrated the value of using tumor microvessel density as a prognostic indicator for a wide range of cancers. In this context, measurement of microvessel density facilitates assessments of disease stage and the likelihood of recurrence and helps guide treatment decisions. Recently, however, it has been assumed by some investigators that measurements of microvessel density may also reveal the degree of angiogenic activity in a tumor. Based on this assumption, quantification of microvessel density is thought to constitute a surrogate marker for the efficacy of antiangiogenic agents as well as a means by which to assess which patients are good candidates for antiangiogenic therapy prior to treatment. Here we contend that, although microvessel density is a useful prognostic marker, it is not, by itself, an indicator of therapeutic efficacy, nor should it be used to guide the stratification of patients for therapeutic trials. In this review, we discuss the evidence for these assertions and what can and cannot be determined from measurements of microvessel density.