Most recently, we have proposed absolute levels and posttreatment fluxes in measurable circulating tumor cells (CTCs) as useful surrogate markers for systemic therapy of advanced disease,[14,15] but this will require validation in well-controlled randomized clinical trials. Further studies would be needed to demonstrate whether CTCs are relevant in the management of localized prostate cancer. Real progress can only be achieved by increasing the participation of our patients in structured clinical trials,[16] analogous to those of the breast cancer community.
The Screening Debate
Perhaps the most vexed issue in early-stage prostate cancer, and the one with the most general impact, is the issue of community-wide screening. The true definition of “screening” refers to the assessment of asymptomatic members of the general population for a particular disease, and requires that when the process is successful (with early identification of the disease), it will result in decreased morbidity of treatment or reduced overall mortality. For many years, an accepted “truth” in the urologic community has been that screening for prostate cancer should be innately beneficial, based on the fair concept that earlier diagnosis is associated with a lower potential for occult established metastases and a higher potential for cure by local therapeutic means. While the theory is attractive, it doesn’t always work out in clinical practice—for example, the failure of annual chest x-rays to achieve improvement in survival from lung cancer in structured clinical trials.
In support of the concept, which has been advocated by influential organizations such as the American Urological Association (AUA) and the American Cancer Society (ACS), it has been claimed that improved outcomes in communities that employ screening of asymptomatic patients are due to those screening activities. For example, the percentage of patients presenting with advanced-stage disease and of those dying from prostate cancer in the Austrian Tyrol, compared to those diagnosed, has fallen since the introduction of routine screening techniques.[17] Similarly, it is claimed that the death rate from prostate cancer has fallen in the United States since the introduction of PSA measurement in the 1980s.
The counterargument is that any increment in survival may also be due to improved patient education, more accurate diagnostic and staging techniques (also contributing to stage migration), a more active approach to salvage care by clinicians (accompanied by improved salvage therapies), and the impact of combined-modality treatment on locally advanced disease. Furthermore, the statistic of absolute number of deaths from prostate cancer in the United States has hovered in the range of 26,000 to 30,000 per year since the 1980s, when PSA testing first became widespread. In the definitive ACS Cancer Statistics overview in 1985, it was noted that there were an estimated 24,000 deaths from prostate cancer.[18] In the equivalent data set from 2007, the estimate was 27,050[19]—hardly a quantum leap forward!
Furthermore, it has been clearly shown that 30% to 50% of men over the age of 60 years have occult prostate cancer present,[20] and yet a vastly smaller proportion of that community succumb to the disease, indicating considerable heterogeneity of its natural history. Finally, there have been previously no published randomized trials of screening for prostate cancer. For these and other reasons, the American College of Physicians and the Agency for Health Care Policy and Research have declined to recommend routine screening of asymptomatic men.
Bottom Line
This year, for the first time, two seminal randomized trials of community screening for prostate cancer have been published.[21,22] The results have been scrutinized, interpreted, manipulated, and discussed ad nauseam at meetings and in print, and do not bear detailed recitation here. However, the bottom line is important: viz, neither trial demonstrated a statistically significant overall survival benefit from screening large numbers of asymptomatic males. No matter how you play with the data, an overall survival benefit was not shown, despite overdiagnosis and treatment of some patients.
While some might accept Benjamin Disraeli’s wry comment about “lies, damned lies, and statistics” when considering the new data, these studies did not provide evidence to support unstructured community-wide screening. Indeed, it is puzzling that the AUA continues to advocate this approach, presumably hoping to save a proportion of those who might die from prostate cancer, at the expense of overtreating many who are not destined to succumb to the disease.
The problem is to identify which patients have potentially bad disease, and thus, this commentary has come full circle. Hopefully the laboratory will provide the answer. Until then, it is essential that we educate our patients, inform them of the options and the available data, identify our own conflicts of interest, offer participation in well structured clinical trials, and if possible, avoid doing harm.
