Detecting Prostate Cancer Without Overtreatment Is Difficult

A difficult line to walk in some cancer types is that between widespread screening to detect early disease and lower the death rate versus the overtreatment and associated consequences that can arise from it. This is particularly true when it comes to prostate cancer.

There has been a lot of debate about screening in asymptomatic men to check blood levels of prostate-specific antigen (PSA), a protein that tends to rise when prostate cancer is present. It’s an imperfect test, since rising levels of PSA can indicate issues other than cancer, but it’s the best way to screen that’s available now.

PSA screening was once widely administered as part of routine wellness visits, but that changed in 2008 after the U.S. Preventive Services Task Force (USPSTF) advised against it in men 75 and older, and again in 2012 when the task force recommended against its routine use in all men. In 2018, the task force relaxed its rules, suggesting that men 55 to 69 make individual decisions about whether to screen but that men 70 and over should not take the test.

According to a study discussed in this issue of CURE®, the rate of advanced prostate cancer in men 50 or older demonstrated an upward swing between 2005 and 2016, while the frequency of early stage prostate cancers dropped. The study’s authors believe those changes may be a direct result of the USPSTF’s recommendations, which were based on concerns about overtreatment — biopsies and therapy that can cause side effects and lower the quality of life in men whose disease, if undetected, would never have
harmed them.

At the time the USPSTF made its recommendations, one large clinical trial had demonstrated a benefit associated with PSA screening, but two others had not. However, it was discovered later that one of the trials that showed no benefit, due to faulty data analysis, had underestimated the testing’s value. According to a recent analysis, that trial and the one that originally showed a benefit now agree that there was a 25% to 30% relative reduction in the risk of prostate cancer death in men who had screening compared with no screening.

Yet, based on the USPSTF’s recommendations, a smaller number of men were screened. That surely saved some patients from overtreatment, but at the same time it seems to have driven up the rate of advanced prostate cancers. Another problem with skipping screening is that it can deny men with low-grade prostate cancers the option of undergoing active surveillance so they will know if their disease starts growing quickly and needs more aggressive therapy.

So far, we have not seen a rise in death rates from prostate cancer; in fact, there was a marked decline between 1993 and 2017, but it may be too soon to see an effect from the decline in screening. In any case, it’s crucial to the well-being of patients that we move the diagnostic trend toward finding disease before it has reached advanced stages.

In our article, researchers discuss ways to strike a balance between the harms and benefits of PSA screening by customizing the process, including spacing out the tests and screening only those under age 70. Other advancements could include refining active surveillance for men who have elevated PSA and lower-grade disease and creating new diagnostics, such as DNA-based technologies and systems that measure how quickly PSA levels rise over time. Needed just as much are strategies that will help patients and their doctors choose the most appropriate treatments or monitoring techniques.

All of these developments will help ensure that patients receiving local therapies such as radiation or surgery will have the best chance at longevity without experiencing life-changing side effects from either their disease or therapy — and that those who don’t need treatment can avoid it.

Researchers and clinicians are working on the different parts of this puzzle, and early diagnostic technologies are advancing quickly, yet it is difficult to say when the next version of prostate cancer screening guidelines will be able to reflect this progress and bring the PSA screening debate to a close.