Identification of Clinically Useful Cancer Prognostic Factors: What Are We Missing?

The number of cancer prognostic markers that have been validated as clinically useful is pitifully small, despite decades of effort and money invested in marker research ( 1 – 3). For nearly all markers, the product has been a collection of studies that are diffi cult to interpret because of inconsistencies in conclusions or a lack of comparability. Small, underpowered studies; poor study design; varying and sometimes inappropriate statistical analyses; and differences in assay methods or endpoint defi nitions are but a few of the explanations that have been offered for this dis-appointing state of affairs ( 4 – 11). Researchers attempting to con-duct meta-analyses of prognostic marker studies encounter many diffi culties ( 12 – 14). In this issue of the Journal, a meta-analysis by Kyzas et al. ( 15) of the tumor suppressor protein TP53 as a prognostic factor in head and neck cancer provides compelling empirical evidence that selective reporting biases are a major