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

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... int defi nitions are but a few of the explanations that have been offered for this disappointing state of affairs ( 4 -11 ) . Researchers attempting to conduct 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 impediment to conducting meaningful meta-analyses of prognostic marker studies. These biases have serious implications, not only for meta-analyses but also for interpretation of the cancer prognostic literature as a whole. Kyzas et al. demonstrate bias in the estimated association between TP53 status and mortality relating to a number of factors. The prognostic importance of TP53 decreased as the pool of included studies increased from published and indexed studies to any published studies, and then to the full set of all published and unpublished studies with retrievable data. In addition, when marker positivity defi nition and choice of clinical endpoint were retrospectively partly standardized across studies, there was a decrease in the overall estimated association compared with that obtained when each study used its preferred marker positivity criterion and endpoint. The authors are appropriately cautious in acknowledging that confi dence intervals for the estimates across the different analysis sets do overlap and that one cannot determine what might have been the effect of additional nonretrievable data on the observed trends. Nonetheless, we believe that this study provides the most compelling evidence yet that the published prognostic