2021

Peter R. Carroll, MD, MPH, Professor of Prostate Cancer and Urology at the University of California, San Francisco, examines data from randomized controlled trials that studied prostate-specific antigen (PSA) testing and mortality. He emphasizes that data show that the number of patients screened and diagnosed to avoid one death improves significantly over time and thus it is important to recognize the long-term impact of screening. Dr. Carroll briefly discusses American Urological Association (AUA), U.S. Preventive Services Task Force (USPSTF), American Cancer Society (ACS), and National Comprehensive Cancer Network (NCCN) recommendations, noting that some recommendations are vague with regard to biopsy. Dr. Carroll then displays a pictogram of what he calls “the Achilles heel of PSA screening.” It shows that among 1,000 men in the US, about 250 have an elevated PSA. If all patients with elevated PSA are biopsied, the results show that half have no disease and, of the remaining men, about 30-40 percent have low-risk disease. He cites harmful effects of overtreatment, mentioning sepsis as an example, but concludes that the harms outweigh the benefits in this screening paradigm. Dr. Carroll then explains that detection paradigms have changed from a “detect all, treat all” approach to a “detect some, treat some” approach, utilizing surveillance for patients with lower-risk disease. Dr. Carroll outlines NCCN Guidelines for 2021, which include a continuation of support for early detection efforts; baseline testing at age 45; germline testing; an acknowledgment that optimal screening of high-risk patients (e.g., African-American men) is not completely known; provisions for alternatives to routine biopsy; and a recognition of the value of active surveillance for low-risk cancers. He highlights the recommendation that digital rectal examination (DRE) should be used as a complement to PSA testing, not as a standalone screening test. Dr. Carroll concludes that DRE could not be implemented effectively in a nationwide screening program. Dr. Carroll explains that, increasingly, doctors are opting for tests of specificity (biomarker or MRI) before opting for biopsies. He asserts the value of using MRI before biopsy, since MRI targeting increases the detection of high-grade cancers while limiting the detection of low-grade cancers. However, he explains that a decision not to biopsy requires use of a biomarker test along with MRI, since the negative predictive value (NPV) of MRI is 85 percent. He cites the PROMIS trial and asserts that a negative MRI alone is insufficient. Dr. Carroll then cites data from a recent trial in the NEJM showing that MRI-targeted biopsy decreases the likelihood of negative or benign biopsy and testing with biomarkers can reduce biopsies by 20-65 percent while missing few (2.5-8 percent) high-grade cancers. He asserts that recent studies suggest that upfront biomarker testing with conditional MRI may be the most efficient strategy for early detection, with cost and availability being strong considerations. He supports this assertion with data on various biomarker tests as well as early detection algorithms. Dr. Carroll returns to the NCCN recommendations on management of biopsy results before concluding his discussion, reemphasizing that prostate cancer early detection in well-informed, healthy men saves lives.