Evidence-Based Medicine, Conscience-Based Medicine, and the Management of Low-Risk Prostate Cancer
Authors: Anthony Zietman
Journal: Journal of Clinical Oncology (2009)

What began as a small crack in the solid concept of early detection and early treatment for prostate cancer has now widened and spread. Despite imperfections which limit their interpretation, the recently published randomized screening trials show there is only a small—or even no—improvement in survival from early detection over the first 10 years. One trial also showed that the number of patients (around 50) that must be treated to save one life is alarmingly high. These data come at a time when medical spending, long recognized to be beyond the nation’s means, is to be tightened and restructured along evidencebased guidelines with care being directed preferentially toward areas of proven benefit. The Institute of Medicine has drawn up national priorities for comparative effectiveness research, and the management of localized prostate cancer sits squarely in the first quartile. Indeed, it is the top-ranking oncologic priority. A perfect storm of clinical evidence and economic reality has arisen in which urologists and radiation oncologists need to examine the evidence, examine their souls, and start to carefully look at every new patient asking, before anything else—is treatment really needed at all? If it is not, and that will frequently be the answer, then they must be prepared to lead the patient along the less financially rewarding and decidedly unglamorous path of active surveillance. The training of resident doctors has to date been so focused on cure, and the culture of early detection/early treatment so deeply in-grained, that it is little wonder that this shift in thinking is yet to reflect itself in everyday practice. What is respectfully acknowledged at major meetings and in editorials is not, in the daily reality of the clinic, being applied to patients. Indeed, in the United States, the proportion of men being managed conservatively has actually been declining. The explanations, as hinted, are complex and rooted in a conflict between knowledge and belief with disturbing undertones of economic self-interest. It is time to practice consciencebased medicine. The PCPT (Prostate Cancer Prevention Trial) trial reported in 2004 demonstrated that systematic needle biopsy could find prostate cancer in 27% of all men with a normal prostate-specific antigen (PSA). Klotz has estimated that at current rates, one in five men will be diagnosed with prostate cancer during their lifetime. We know from the days when no attempt at curative treatment was the norm that no more than 3% of men ever died from this disease, and more recent experience tells us that a significant proportion of men are incurable even when their disease is detected early. Large mismatches between incidence and fatality occur elsewhere in medicine and have been reconciled in different ways. How this has been reconciled in prostate cancer forms the kernel of this debate. Until recently, United States physicians and advocacy groups have strongly favored immediate, curative treatment for all or most men with early prostate cancer. They have argued that this is little different from the treatment of high blood pressure or high serum cholesterol, strategies almost universally applauded. To address prostate cancer differently, it has been said, would be to apply double standards. The absolute risk reduction of stroke or a coronary event is low for any individual but treatment for the entire diagnosed population is justified because the treatments are effective, well tolerated, and relatively inexpensive. How does therapy for prostate cancer compare? Firstly, is it effective? The Scandinavian trials of both surgery and radiation therapy prove that some men with clinically significant, life-threatening, localized disease live longer as a result of their treatment. At 10 years, 19 men in one trial and 10 in the other needed treatment for a single life saved in a relatively advanced, nonscreen detected group of patients. It is far from clear, however, that low-risk, PSA-detected patients, such as we now most commonly see, would ever progress to the starting line to even enter the Scandinavian trials. Thus, the gains in a screen-detected population must be smaller, and the European Trial of Prostate Cancer Screening (ERSPC) has borne this out. Further, in the surgical study, the benefits were only seen for men younger than 65 years. This is important, as screening in the United States now frequently continues well beyond the seventh decade. Tens of thousands of men in their 70s and 80s are being diagnosed with early prostate cancer, men who have relatively little, if anything, to gain from either knowledge of the diagnosis or treatment. It is argued that there are advantages to a patient short of a saved life. They may be prevented from troublesome local progression and spared the misery of future androgen deprivation. Contemporary data do show that local failure is now infrequent after radical treatment but it is also true that symptomatic local progression is unlikely even without treatment and thus little, in reality, is gained. In addition, Barry has shown that, far from reducing the use of androgen deprivation through a reduction in metastases and local progression, our heightened responsiveness to the behavior of PSA after therapy has actually increased its use substantially. Many feel that technological advances have tremendously reduced the morbidity and increased the convenience of both surgery and radiation such that they can be regarded as little different from a statin or an antihypertensive. Unfortunately, multicenter studies continue to document a significant impact on the quality of a patient’s subsequent life, suggesting that this is not the case. If treatments were usefully curative in only a small proportion of patients and really could be made free from all but trivial morbidity could they still be judged sufficiently cost-effective to justify their widespread use? This, of course, depends on the costs of treatment and their future trajectory. In the United States, the costs of prostatectomy have been declining due to better anesthesia, better postoperative pain control, and shorter hospital stays. This is laudable, though recently widespread investment in costly robots to gain a market rather than a therapeutic edge may work against this. Radiation therapy has been headed in two different directions. Brachytherapy became popular in the 1990s due to its speed and convenience. It also happened to be remarkably inexpensive and something of a therapeutic bargain. Unfortunately, recent concerning disclosures Editorial