<p>There are a growing number of techniques aiming to distinguish clinically significant prostate tumors from clinically insignificant ones in men with an elevated prostate-specific antigen (PSA) level. Ideally, there should be a balance between detecting clinically significant prostate cancer and avoiding the overdiagnosis of incidental low-grade disease, especially in older men or in those with significant comorbidity.</p>

In 2012, the US Preventive Services Task Force (USPSTF) gave the PSA test a D rating. From then until it was adjusted to a C rating in 2018, primary care physicians were told not to screen for prostate cancer, and a lot of damage regarding routine screening for prostate cancer was done. PSA testing is not perfect, but I would argue that it remains the best basic initial screening test that we have for prostate cancer. Sadly, I think that there is still a lot of confusion surrounding PSA testing because various guidelines still have slightly different messages about it.

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I think that more physicians are mindful that they do not want to overdiagnose incidental and non–clinically significant prostate cancer. Prostate multiparametric magnetic resonance imaging (MRI) has really taken off as an adjunct to further work up an elevated PSA. The idea is to biopsy only the lesions that show up on MRI and not to perform standard systematic biopsies, thus avoiding overdetection. However, at our practice at Duke—and I suspect at many others—almost everyone gets both the fusion and the standard biopsies. So, we are detecting more cases of clinically significant prostate cancer, but we are likely not really decreasing the number of low-grade prostate cancers that are detected. In addition, prostate MRI quality has likely decreased a little because a lot more MRIs are being performed and read outside of centers of excellence. Some quality-assurance issues are probably making real-world data less robust than what was reported in some of the original literature.

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In day-to-day practice, we often use PSA testing in combination with blood and urinary marker testing, especially in patients with a borderline PSA level. We have had success with a mail-order test that measures the gene expression of 3 RNA biomarkers in exosomes in the urine. It was granted US Food and Drug Administration (FDA) breakthrough designation and is used in men aged 50 years or older who have a total PSA level between 2 and 10 ng/mL and are being considered for a prostate biopsy. Studies have found that it has a 91% negative predictive value for medium- and high-grade prostate cancer, defined as a Gleason grade group 2 or higher. When the test score was below 15.6, only 7.9% of patients had high-grade prostate cancer after 2.5 years. Our practice and many others are using this to avoid unnecessary biopsies because it is a good predictor of non–clinically significant disease.

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Has an optimal balance in prostate cancer detection been achieved? The simple answer is no. Although many thousands of men have had their lives saved with screening, there is still room for improvement.