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Do No Harm: How a Magic Bullet for Prostate Cancer Became a Medical Quandary
By Stewart Justman. 236 pp. Chicago, Ivan R. Dee, 2008. $26. ISBN 978-1-56663-627-8.

n 2003, the Journal published an article on the influence of finasteride in the prevention of prostate cancer. This study demonstrated that men who took the drug experienced a 24.8% lower risk of prostate cancer, as compared with men who received a placebo, but had a higher risk of high-grade disease. This startling finding raised an ethical dilemma about the riskbenefit ratio and the question of whether any risk was too high. Stewart Justman is well credentialed to attack this thorny question. He is a noted author, a professor of liberal studies at the University of Montana, a lay member of the American Society of Clinical Oncologys 5 Alpha-Reductase Committee, and a survivor of prostate cancer. The reader who enjoys medical history and ethics will enjoy Justmans exploration of historical figures ranging from Socrates to Ren Descartes and from John Locke to Joseph Lister to William Osler, as well as his exploration of the tragic outcome of experimental surgery for a club foot in Gustave Flauberts Madame Bovary. Modern examples of adverse outcomes from treatment with diethylstilbestrol, rofecoxib (Vioxx), and tamoxifen are also included. In addition to providing this historical perspective, Justman describes ways in which the finasteride investigators appeared to downplay potential side effects or tried to justify them from a population viewpoint. He quotes the statement of a senior author of the Journal article in a news release when the trial was first announced: I am firmly convinced that this is the first step in conquering prostate cancer. In response, Justman writes that the evangelical ring of this proclamation of faith, so contrary to the spirit of both dispassionate inquiry and careful practice, is nowhere to be found in the actual medical literature

on finasteride. He goes on to say, With these trumpet notes still in the air, the story acknowledges the increased risk of high-grade tumors . . . but not until the seventh of nine paragraphs. . . . Justman suggests that if both the benefit of a 24.8% lower risk of prostate cancer and the higher risk of high-grade disease had been presented as percentages in the article (i.e., a 68% higher risk of high-grade disease), surely it would look as if the second offset or overshadowed the first. He also questions whether the gains were really significant. The screening program that was used in the study produced such an inflated rate of diagnosis in the placebo group that even the suppressing effect of a potent drug was not quite enough to bring it down to normal. And he objects strongly when investigators use populationbased statistics to justify what the risk would have to be to cancel out its survival benefits, saying that when they use these techniques, they cease to think like doctors and begin to think like actuaries, statisticians, or investors. Throughout the book, Justman tries to be evenhanded, and he systematically summarizes reports that suggest that the excess in aggressive disease is an artifact because finasteride made it easier to diagnose high-grade disease. However, as he points out, all of these scientific papers conclude that induction of high-grade disease cannot be excluded. How safe should this drug be? Justman uncovers an article that was published in the Journal of Cellular Biochemistry in 1992 a year before the trial began in which a panel on the chemoprevention of prostate cancer suggested that to reduce overall risk in large populations, chemopreventive agents must be entirely free of any side effects. He concludes, Only because of the wellestablished principle of erring on the side of caution does the burden of proof in this debate fall squarely on those in favor of the general use of a drug whose safety is in question. Their arguments must meet a higher standard of evidence, and to this point they have not done so. Justmans case would have been even stronger if he had included a reanalysis of the original trial.

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The New England Journal of Medicine Downloaded from nejm.org on July 24, 2011. For personal use only. No other uses without permission. Copyright 2008 Massachusetts Medical Society. All rights reserved.

book reviews

In the first 7 years, the major effect of finasteride was the prevention of diagnostic biopsies not the prevention of cancer. Because finasteride lowers levels of prostate-specific antigens, men were lulled into a false sense of security, and 15% fewer men who were taking the drug underwent biopsies. This artifactually reduced the number of cancers. However, in the men who actually underwent biopsies, there was no significant reduction in their risk of being diagnosed with cancer. Thus, in the absence of any benefit, Justmans concerns about potential harm are further heightened. Patrick C. Walsh, M.D.
Johns Hopkins Medical Institutions Baltimore, MD 21287

Urological Oncology
Edited by Vinod H. Nargund, Derek Raghavan, and Howard M. Sandler. 634 pp., illustrated. London, Springer, 2008. $79.95. ISBN 978-1-84628-387-1.

he treatment of testicular cancer has been described as one of the true success stories of modern medicine. The contemporary management of this cancer is multidisciplinary incorporating surgery, radiation therapy, and chemotherapy and often achieves durable success rates of more than 90% regardless of the stage at presentation. This multidisciplinary approach has been widely adopted and is currently used for the treatment of many other types of cancer. Therefore, it is not surprising that Urological Oncology was edited by a urologic surgeon, a medical oncologist, and a radiation oncologist. They exemplify the kind of multidisciplinary team that manages urologic cancers. The reader will immediately recognize that this book, with its soft cover and compact design, is not meant to be referred to occasionally, but to be used frequently. What is not immediately evident, however, is how wide-ranging this book is. Billed as a handbook or a quick reference, it is actually a comprehensive textbook that is appropriate for William C. Huang, M.D. clinicians at all levels of training. The contribuNew York University School of Medicine tors are internationally recognized experts in uro- New York, NY 10016 logic oncology, and they include not only on- william.huang@nyumc.org

cologists but also anesthesiologists, diagnostic radiologists, and experts on health outcomes. The books chapters are divided into three parts: Basic Science, Clinical Aspects and Investigations, and Systemic Genitourinary Oncology. The first part deals with the basic principles that underlie the treatment of urologic cancers, and it includes discussion of cellular and molecular pathways and in vitro and in vivo models of different malignant urologic conditions. This section, like the rest of the book, is concise. It will be informative for clinicians who want to understand the scientific foundations of urologic oncology. The second part of the book differentiates Urological Oncology from most other textbooks in the field. It is an overview of the basic principles of radiotherapy and chemotherapy in urologic tumors, with discussions of the principles of clinical trials, the management of clinical emergencies, and even dietary considerations in genitourinary cancers. It is clear from this section that the book was designed to be both practical and didactic. The third part of the book, a discussion of the different urologic cancers, is organized around organ systems. All the major urologic cancers are covered, including a section on nonurologic cancers that affect the urinary tract. The content is up to date and succinct, and it describes advances and controversies in the treatment of each type of cancer. Nearly all of the chapters include tables and figures that summarize pertinent studies and their findings, thereby providing an evidencebased guide for the management of urologic cancers. As a urologic oncologist, I test-drove this book for over a month, and I was thoroughly impressed with how practical, comprehensive, and timely it is. I was equally impressed with how appropriate the material is for clinicians at all stages of their careers, regardless of their subspecialties. This book may be a useful reference for anyone who frequently deals with patients with urologic cancer.

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The New England Journal of Medicine Downloaded from nejm.org on July 24, 2011. For personal use only. No other uses without permission. Copyright 2008 Massachusetts Medical Society. All rights reserved.