Although prostate cancer is remarkably frequent among men, the availability of non-invasive early detection methods, such as PSA blood levels tests and digital rectal examination, greatly facilitates its detection and subsequent treatment. However, a recent update of a clinical trial performed over 19 years suggests that implementing a systematic prostate cancer screening program using these methods may not decrease mortality.
Approximately one out of seven men in Canada are at risk of developing prostate cancer (PC) at some point in their life. Despite this remarkably high incidence rate, the five-year survival rate associated with PC is 96%, which can be partially explained by the availability of rapid and non-invasive diagnosis methods. Among them, monitoring blood Prostate Specific Antigen (PSA) levels and performing Digital Rectal Examination (DRE) are the most routinely performed. Elevated blood levels of PSA, a peptidase secreted by prostate epithelial cells, are associated with PC.
However, the potential benefits of implementing a PC screening program based on these detection methods remain controversial in part because many PC clinical cases remain asymptomatic throughout the life of an individual. Therefore, it has been suggested that such programs may also lead to overtreatment, which can impart negative consequences on the quality of life and health of the patient, as well as waste of financial resources. Moreover, two independent clinical studies reported conflicting results regarding the mortality of patients undergoing a PC screening program, with one study claiming a 20% reduction while the other reported absolutely no benefit even after 13 years of follow-up.
In order to more accurately assess potential long-term consequences of PC screening programs on mortality, the latter study, which initially involved more than 75,000 men, was pursued for an additional six year time span. Half of the subjects were assigned to a treatment group in which patients were provided DRE and PSA testing annually for five years and the the other half was a control group. The results were recently published in Cancer by an NIH-affiliated group led by Dr. Paul Pinsky. The authors were mainly interested in assessing the death rate and suggested that the benefits of PC screening, if any, need to translate into a substantial decrease of mortality to outweigh the harms imparted by overtreatment. Their results unequivocally fail to meet this criterion, with absolutely no observed benefit imparted by PC screening (255 PC deaths in the treatment group compared to 244 in the control group). The cumulative distribution of deaths across the 19 years over which results were compiled does not show any difference either. Moreover, the authors note that in both groups, about 60% of all deaths can be attributed to PC cases diagnosed within the first six years of the screening phase, suggesting long-term assessment of mortality is instrumental to determine the impact of PC screening strategies on mortality.
However, it is important that their results are not interpreted as a demonstration that PSA and DRE are useless in preventing mortality associated to PC. Indeed, the vast majority (86%) of the patients in the control group had their PSA blood levels monitored at some point in their life and many of them underwent PSA tests during the trial period, albeit for non-screening purposes. Thus, the correct interpretation is that implementing systematic PC screening programs may not impart additional benefits compared to opportunistic testing for PC. Finally, this study does not provide any data about the costs and incidence of cancer overtreatment, which makes it even more difficult to say whether the balance tilts in favour of the harms or benefits of PC screening programs.
Written By: Samuel Rochette, M.Sc