Edward P. Gelmann, MD; Susan M. Henshall, PhD
Potential Conflicts of Interest: None disclosed.
Gelmann EP, Henshall SM. Relevance of Molecular Markers in Prostate Cancer. Ann Intern Med. 2009;151:894-895. doi: 10.7326/0003-4819-151-12-200912150-00017
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Published: Ann Intern Med. 2009;151(12):894-895.
Dr. Concato and colleagues make 3 major points. First, they say that their study determined whether marker status at diagnosis (vs. after surgery) predicted actual mortality and emphasized the importance of not assuming that biochemical failure is an outcome equivalent to mortality. Second, they explain that their results can guide future research on biological mechanisms and suggest new approaches to therapy. Third, they cite other reviews as affirming the importance of the 3 markers they highlighted: P53, BCL2, and microvessel density. We commend Dr. Concato and colleagues for assembling a large and important study cohort. However, in trying to identify important prognostic markers, the authors did not surpass the power of Gleason scoring or directly compare their data with histologic grade in their search for clinically useful prognostic indicators. Finally, Dr. Concato and colleagues did not address the possibility that these markers are predictive of response to various therapies as well as prognostic. Thus, the use of irradiation, hormonal therapy, or chemotherapy should have been taken into account in the analysis (1). We also draw attention to the guidelines by McShane and colleagues (2), which set criteria for studies of prognostic markers. Although the data presented by Dr. Concato and colleagues do not adhere to many of these guidelines, we were most concerned that the assay methods were neither properly validated nor set forth in a manner that allowed replication and confirmation by others. Moreover, we noted that the study had insufficient statistical power to demonstrate the effect of BCL2 expression, which seemed to be the most promising marker. Finally, the choice of markers was not well justified either by the literature or by the potential of the markers to be of practical use clinically. Further insight into the biological processes underlying aggressive disease is limited by the focus on known prostate cancer genes examined independently in published studies. We reaffirm our conclusions that P53 and microvessel density will not find application in clinical practice and that the utility of BCL2 awaits validation by studies that are adequately powered and include methodology consistent with published guidelines.
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