Can Increased Utilization Of Active Surveillance Rescue The Survival Benefits Of PSA Screening?

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology
Article Date: 10 Sep 2009 - 0:00 PDT

email to a friend   printer friendly   opinions  

UroToday.com - In the lay press and in Washington, prostate cancer has emerged as a litmus test for our health care conundrum of overtreatment and soaring costs in the setting of limited evidence regarding benefit.

Despite a 30% reduction since the advent of PSA screening in the number of annual American prostate cancer deaths, the recent publication of very early results from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and American Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trials of PSA screening has fueled a shift in the pendulum of cancer detection policy towards the notion that public health may somehow be better served by avoiding the diagnosis and treatment of prostate cancer altogether. This ominous perspective has been further fueled, in part, by rising costs of prostate cancer care consequent to expensive treatment innovations such as intensity modulated radiotherapy, proton beam therapy, and robot-assisted laparoscopic surgery, that have gained popularity with sparse evidence as to whether the incremental benefits of these innovations are worth the higher costs.

The challenge of prostate cancer "overdiagnosis" and subsequent overtreatment could be resolved, however, through increased adoption of active surveillance (AS) coupled with selective treatment. This strategy for prostate cancer care has the potential to mitigate the problem of overtreatment, yet retain the benefit of reducing prostate cancer death through screening-based early detection.

The PLCO trial identified no mortality benefit from combined screening with PSA testing and digital rectal examination , whereas the ERSPC reported a 20% relative reduction in the death rate from prostate cancer at a median follow-up of 9 years. Both studies have been widely cited to suggest that the benefits of PSA-based screening may be outweighed by the overdiagnosis of clinically-insignificant prostate cancer, as the ESPRC reported that 1400 men need to be screened to prevent one death from prostate cancer. While these studies were accomplishments in both scope and size, several important limitations warrant emphasis to avoid misinterpretation of these studies as evidence against PSA screening.

First, PSA screening was present in the control groups of both studies. This problem significantly confounded the PLCO trial as PSA and DRE testing was performed in half or more of control arm patients who had been randomized to not undergo screening. This contamination of the "control" group renders the PLCO findings as essentially incapable of evaluating the effects of PSA screening because both arms, despite randomization, were screened. Not surprisingly, the proportion of cancers identified in the control arms of both studies that were clinical stage I - cancers found due to elevated PSA - was similar to those in the "screened" arms of the trials. Additionally, the median follow-up for patients in the PLCO trial was only 6 years. This was two years prior to when changes in disease-specific mortality were identified in the ERSPC cohorts; therefore, emerging differences may not have occurred at this early time point in the PLCO study. Together, these limitations likely underestimate any benefits of PSA screening that may have been identified in the PLCO trial.

Subsequently, the AUA has issued new guidelines offering PSA screening to men aged 40 and above with individualized screening thereafter. Abnormally elevated PSA at a young age is predictive of future prostate cancer risk, and earlier PSA screening may identify patients with high-risk prostate cancer for whom early intervention provides benefit. For patients found to harbor low-risk, early-stage prostate cancer, AS may be utilized to defer therapy but still allow for definitive therapy at a later date without compromising outcomes.

As experience with AS has grown, studies have demonstrated that it is both feasible and safe in men with early-stage, low-grade prostate cancer. In carefully selected patients, deferring therapy has not been shown to compromise cancer control. However, unsettled issues remain, including: determining selection criteria for AS; defining the optimal surveillance schedule; incorporating of imaging modalities in addition to PSA and biopsy for patients on AS; identifying new biomarkers to recognize aggressive disease; and characterizing the psychosocial impact of expectant management on patients with prostate cancer. Current research efforts in these areas will aid in the implementation of AS for interested patients and physicians.

An individualized plan for early detection management of low-risk prostate cancer that balances patient risk with treatment morbidity and survival benefit can circumvent the conundrum of overdiagnosis through the selective use of active AS. Studies are needed to better delineate how such AS strategies can be used to reduce overtreatment and optimize quality of life while maintaining the survival benefits of selective definitive treatment.

Written by Sandip M. Prasad, MD and Martin G. Sanda, MD* as part of Beyond the Abstract on UroToday.com

*Corresponding Author: Martin G. Sanda, M.D. Rabb 440 - 330 Brookline Ave Division of Urology Beth Israel Deaconess Medical Center

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from UroToday, go to: www.urotoday.com

Copyright © 2009 - UroToday

• Additional
• References
• Citations