PSA testing for prostate cancer: balancing the benefits and harms

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Routine screening of prostate-specific antigen (PSA) levels in men to detect prostate cancer is very controversial. The higher the level of PSA in the blood, the more likely it is that a man has prostate cancer, and the PSA test has been widely used to screen for prostate cancer and monitor treatment response in those diagnosed with the disease. However, elevated PSA levels can also be indicative of prostatitis or a urinary tract infection, so the test can suggest the presence of prostate cancer when no cancer exists.

International consensus committees are divided inistock photo their recommendations about PSA testing. The New Zealand Ministry of Health recommends that all men over 50 should check for symptoms and undergo annual PSA testing. In the UK, however, routine PSA screening is not recommended, and men over 50 are only entitled to a PSA test if they have first discussed the benefits and harms with their doctor. The US Preventive Services Task Force (USPSTF) advises against PSA screening; co-chair Michael LeFevre highlights that:

“There is a very small potential benefit and significant potential harms”

 

Why is PSA testing so controversial?

International recommendations about PSA screening differ because the risk:benefit ratio of regular testing is unclear. On one hand, the PSA test can detect early signs of prostate cancer, leading to prompt treatment, which can prevent the cancer from progressing. The European Randomized Study of Screening for Prostate Cancer (ERSPC) found that regular PSA screening reduced the risk of dying from prostate cancer by around 20%, supporting the view that testing can save lives. However, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial showed that regular PSA screening did not lead to fewer prostate cancer deaths.

Many experts believe that PSA testing does more harm than good because of false positive results, unnecessary anxiety and overtreatment. Removal of the prostate gland can lead to incontinence and erectile dysfunction, having dramatic impact on quality of life, and some tumors detected through PSA testing grow so slowly that they would probably not be life-threatening. Therefore, the USPSTF recommends that the benefits of PSA screening do not outweigh the harms.

 

 

How can the PSA test be improved?

There is a clear need to improve the PSA test in order to better predict which men will benefit from regular screening. In a research article published in BMC Medicine as part of our Personalized medicine: genes, biomarkers and tailored treatment collection, Andrew Vickers and colleagues from Memorial Sloan Kettering Cancer Center showed that prostate cancer overdiagnosis is strongly linked to age and PSA level.

Reanalyzing data from the Surveillance, Epidemiology and End Results (SEER) database, as well as from two randomized clinical trials, the authors showed that if PSA testing was only carried out in younger men, or restricted to those with a baseline PSA level of >1ng/ml in men over 60, overdiagnosis would be substantially reduced.

Importantly, these results indicate that if PSA screening  was carried out in a more selective way, the harms associated with overdiagnosis could be reduced. Vickers explains that:

“Overdiagnosis is generally thought of as an unavoidable aspect of PSA screening. We show that overdiagnosis is highly predictable, being mainly found in older men and those with lower PSAs. As such, restricting screening to younger men, and those with above average PSAs, could dramatically decrease overdiagnosis rates”

Providing further support for selective PSA testing, recent istock photoresearch showed that men with the BRCA2 gene mutation are at increased risk of having intermediate- or high-risk prostate cancer than those not carrying the mutation, suggesting that screening could be targeted based on an individual’s genetics to reduce the potential harms.

In a recent study published in BMC Urology, Owen T Hill and colleagues demonstrated that evaluating biomarkers such as hemoglobin and creatinine together with PSA levels can help to detect clinically relevant prostate cancer. These findings provide further insight into how PSA screening can be individualized so that invasive biopsy and treatment can be tailored to those who will benefit most.

These studies highlight how PSA screening can be targeted based on patient characteristics, genetics and biomarker levels. Future investigations should provide additional insight into how PSA testing can be targeted towards specific individuals, and we look forward to seeing whether more personalized screening will tip the balance in favor of beneficial screening for those who need it most.