The factors contributing to the rise in metastatic prostate cancer incidence rates observed in the United States are much debated; however, many point to changes in screening guidelines. Peter R. Carroll, MD, MPH, discusses the ever-evolving prostate cancer screening landscape and modern clinical strategies, including the incorporation of magnetic resonance imaging (MRI), that should prioritize a risk-adapted approach.

The rate of metastatic prostate cancer rose after the US Preventive Services Task Force (USPSTF) recommended against screening in 2012. The USPSTF adjusted these guidelines in 2018, advocating for shared decision making in men younger than 70 years of age. The risk of not screening for prostate cancer is that you will fail to detect those men with disease that could be treated early to avoid metastases. However, the question remains: How many people do you put at risk of receiving unnecessary treatment? I think it is clear that screening does save lives, but the controversy is: How many lives, and at what cost? The USPSTF is currently developing updated draft recommendations.

I used to think that the way to deal with overdetection was with active surveillance for men with low-risk disease and for selected men with intermediate-risk disease. The University of California, San Francisco was an early adopter of this. The problem is that we still see patients with low-risk disease being overtreated. For many, the key now is simply not to diagnose low-risk disease. This is a paradigm shift, and this is why you have seen an increased use of MRI and serum and urine biomarkers that improve the specificity of prostate-specific antigen (PSA) to detect clinically significant prostate cancer. So, instead of doing a biopsy based just on the PSA level, you perform secondary testing to determine which men with elevated PSA levels are truly at risk for significant disease. By doing this, you can decrease biopsy rates by approximately 20% to 50%. Although such testing does reduce overdetection, it is not eliminated. You still have to deal with the appropriate management of low-risk disease, but it becomes less of a problem.

It is clear that a baseline PSA at age 45 years (or earlier in high-risk men) is a strong predictor of the patient’s future risk of cancer and high-grade disease. For men at increased risk (ie, Black men, those with a very strong family history of prostate cancer [eg, first-degree relatives, early-onset disease, and lethal disease], and those with documented germline mutations), earlier testing at age 40 is recommended. From there, you can tailor the screening efforts, with retesting at intervals based on the initial PSA, minimizing the frequency of testing in many patients. I personally believe that obtaining a baseline PSA earlier is better than later in healthy men. With that said, whether to test should be an informed decision, and this, of course, depends on the provider’s thoughts on PSA and the patient’s understanding of it. There are ongoing studies in the United Kingdom assessing the best tool for screening (eg, MRI, polygenic risk scores, or PSA) and the outcomes of such screening. A biobank will allow for the testing of other promising biomarkers.

It is important to realize that most PSA tests are ordered by primary care providers, not urologists. Therefore, efforts at better providing evidence that supports early detection efforts in relevant populations of men are a critical initial step. At the University of California, San Francisco, guidelines have been put in place for internists on when to consider a referral to urology.