Louisville Medicine Volume 67, Issue 2 | Page 27

Force (USPSTF) to downgrade their recommendation for prostate screening in 2012 (2,3). The overall concern of the USPSTF was that prostate cancer screening was exposing patients to unnecessary prostate biopsies, leading to overdiagnosis and over-treatment of clinically insignificant prostate cancer. With the USPSTF downgrade came a decline in prostate cancer screening; the effects of which have been noticed within the urologic community. Follow-up studies into ERSPC and PLCO have exposed potential design flaws and biases that had urologists questioning the valid- ity of their outcomes. Control group PSA testing contamination, screening group compliance issues, and high rates of pre-study PSA testing have been some of the justified criticisms. Repeat analysis of ERSPC and PLCO controlling for some of these flaws and bi- ases has concluded that there was a 25-30% reduction of prostate cancer specific mortality with PSA screening (4). Additionally, in the years following the USPSTF downgrade, rates of localized prostate cancer dropped, while conversely an increased incidence of late-stage advanced disease was noted (5). These observational findings sparked the urology community and the USPSTF to refine their recommendation on screening. Professional societies and urologists have now collectively decided to bring PSA testing back into mainstream with supplemental management strategies and tools to better serve providers and patients. Instead of screening all adult men, the USPSTF and the National Comprehensive Cancer Network (NCCN) now recommend indi- vidualized screening in properly selected men after shared decision making with their provider. Per NCCN guidelines, PSA and DRE screening should be offered to men age 45-75 years of age, and only considered in men >75 years of age if they are very healthy with no significant comorbid conditions. Referral to a urologist should be arranged for a rising PSA and/or a PSA > 3ng/mL (or even lower for those patients at high risk: African-Americans and those with a strong family history of prostate cancer or BRCA mutations). Now that prostate cancer screening is back into mainstream, it remains imperative for urologists to limit unnecessary prostate biopsies. Historically, an elevated PSA triggered a reflex biopsy. In the modern PSA era, there are newly developed tools and management strategies that have been validated to work in conjunction with the PSA test. Supplemental markers such as percent free PSA, kallikrein, PCA3, and exosomal RNA have aided urologists and patients in decision making for acting upon an elevated PSA. In addition to novel second-line markers, urologists have begun using prostate MRI to increase the detection rate of clinically significant prostate cancer. Transrectal ultrasound with MRI fusion technology allows urologists to more accurately target suspicious lesions concerning for significant disease as compared to ultrasound guided biopsy alone. In combination, novel tumor markers and MRI have greatly MEN'S HEALTH aided urologists in lowering the rate of unnecessary biopsies while increasing the detection of clinically significant cancer. Treatment of prostate cancer in the modern era has also changed. Essentially all prostate cancer patients with low risk disease are now offered active surveillance as a viable management strategy. In addi- tion, genetic profiling of tumor RNA and confirmatory MRI fusion biopsy are now being widely used to more accurately risk-stratify patients to support decision making for surveillance. Under close monitoring with a urologist, a growing number of appropriate cancer patients are being managed with active surveillance while avoiding radical treatments such as prostatectomy or radiation. The gap between prostate cancer prevalence and disease specific mortality has challenged urologists to properly identify those pros- tate cancer patients at risk for developing more aggressive disease. PSA testing has re-emerged as a tool the general provider can use to screen their adult male patients after shared decision making, with the understanding that PSA alone is oftentimes not sufficient to justify a prostate biopsy. Furthermore, a diagnosis of prostate cancer does not always necessitate radical treatment. Tumor markers, genetic profiling, MRI and improved biopsy modalities can now be used in conjunction with initial PSA screening to better manage our patients. Providers and patients can be reassured that the era of overdiagnosis and overtreatment of low-risk disease due to an elevated PSA is now over. The urologic community and professional societies now know to use these validated tools to supplement PSA in managing the properly screened patient. Dr. Kartha practices urology at First Urology in Louisville. References: 1. Bell KJ, Del Mar C, Wright G, Dickinson J, Glasziou P. Prevalence of incidental prostate cancer: A systematic review of autopsy studies. Int J Cancer. 2015;137(7):1749–1757 2. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320– 1328. 3. Andriole GL, Crawford ED, Grubb RL, 3rd, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310– 1319 4. Tsodikov A, Gulati R, Heijnsdijk EAM, et al. Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials. Ann Intern Med. 2017;167(7):449–455. 5. Hu JC, Nguyen P, Mao J, et al. Increase in Prostate Cancer Distant Me- tastases at Diagnosis in the United States. JAMA Oncol. 2017;3(5):705–707. JULY 2019 25