PSA Screening for Prostate Cancer Put Into Question By the U.S. Preventive Services Task Force

Based on a review of prostate cancer treatment and screening trials, the U.S. Preventive Services Task Force (USPSTF) has stated that prostate-specific antigen (PSA)–based screening may not be necessary, saying that the potential benefits of the screening do not outweigh the potential harm of complications from evaluations and treatments. The last time the USPSTF reviewed the evidence for prostate cancer screening was in 2008, and the last time the benefits and harms of prostate cancer treatments were assessed was in 2002.

Human prostate specific antigen (PSA/KLK3) with bound substrate from complex with antibody. Source: Wikimedia Commons user E A S.

The analysis of prostate cancer screening clinical trials conducted between 2007 and 2010 showed a small or trivial reduction in prostate cancer-specific mortality and a bigger association with harm rather than benefit. The draft recommendation was published in the Annals of Internal Medicine on October 7, 2011

Currently, PSA screening is recommended to detect prostate cancer earlier in asymptomatic stages, when treatments may be more effective. The analysis sought to address whether PSA-based screening decreased mortality from prostate cancer, the harm of PSA-based screens, the benefits of treating early stage and screen-detected prostate cancer, and the harms of these treatments.

The two recent largest and highest-quality studies, one in the United States and one in Europe, found different results. The European trial reported an association between screening and reduced prostate cancer–specific mortality compared to no screening after a 9-year follow-up (relative risk of 0.8). The Unites States-based trial found no statistically significant effect after 10 years (relative risk of 1.1).

After all of the analysis, the task force found that PSA screening for prostate cancer does not save lives. Instead, there are greater harms from early treatment, including urinary incontinence, erectile dysfunction, and surgical complications. These results are controversial and will likely be the subject of debate among the government panel, doctor groups, and cancer advocacy groups.

The American Urology Association (AUA) rapidly responded with a statement that applauded the interest of the task force in reviewing the PSA screening but said it was "concerned that the task force's recommendations will ultimately do more harm than good to the many men at risk for prostate cancer both here in the United States and around the world," adding that the "PSA test provides important information in the diagnosis, pre-treatment staging, or risk assessment and monitoring of prostate cancer patients." The AUA is preparing its own clinical guidelines on PSA screening and has its own panel of experts that will review usage of the PSA test and early prostate cancer detection.

The CancerNetwork spoke with David Crawford, MD, professor of surgery and radiation oncology at the University of Colorardo about the panel’s announcement. "In 1989 we started Prostate Cancer Awareness Week to educate men about prostate cancer and promote early detection because it was that year that the disease became the number one cancer diagnosed in American males and the second leading cause of death. We had no idea that screening would work, but we did know that the majority of cases of the disease diagnosed then were advanced and incurable."

Crawford went on to say that "as chairman of this group since inception, I realized that we had no level-one evidence to support early detection. Our event was very successful and remains the largest screening event for any cancer in the world. The number of cases of advanced disease plummeted. We found more early cancers, and the the pendulum began to swing too far the other way: We were finding many cancers that appeared to be non-threatening, there was a masterful marketing scheme by a company selling so-called robots and a proliferation of expensive radiotherapeutic techniques. And rather than focus on who needs to be treated, we entered an era of overtreatment in some men."

"At the same time an ongoing U.S. trial called the PLCO demonstrated that screening did not alter mortality. I was the principal investigator for one of the 10 U.S. sites. This trial was ignored by the mainstream, while a weakly positive trial from Europe was embraced. So the U.S. Prevention Task Force have reviewed the data, including the current report which concludes that screening is not appropriate."

Crawford ended by saying "So what should we do? The truth lies somewhere in between. We should not return to 1989 when advanced disease dominated, we should rather prudently screen men and separate diagnosis from treatment. We should strive to determine who could benefit from treatment. We need new markers of aggressiveness. We need to resist the marketing strategies of companies who mislead the public. We should acknowledge the very thoughtful conclusions of this task force and respond during this time of analysis with a plan to evaluate how to somehow irradicate the pain and suffering from this disease. We need to alter the death rate. We should work with organizations like the AUA and others to achieve this goal."

The new recommendations may very well be to do PSA screening, but with more stringent decisions on treatment and further evaluations, also taking into considerations the negative outcomes of unnecessary treatment.