What about starting PSA screening at age <50 years? According to a case-control study by Vickers et al. , men age 45-49 years who have a PSA > 1.6 ng/mL (10% of men) are responsible for 44% of prostate cancer mortalities. So, Dr. Roobol asks, “What about the rest of the patients, is it realistic to delay testing for 10 years?” In her opinion, family history of prostate cancer should be strongly taken into consideration and screening can likely start at 45 years of age in these patients. Ultimately, she thinks that the German ProBase study will provide further clarity as to when we should start PSA testing. The ProBase study is a 50,000-patient prospective, multicenter, randomized (1:1), open label study comparing delayed risk-adapted PSA screening according to a baseline PSA value at age 50 vs risk-adapted PSA screening according to a baseline PSA value at age 45. The primary endpoint is detection of metastatic prostate cancer. Each study participant who meets or exceeds the PSA cut-off of 3.0 ng/mL at baseline or in one of the following screening rounds will undergoing a mpMRI with subsequent stereotactic biopsies of the prostate based on MRI findings and additional random biopsies of the prostate. Each study participant will be screened up to the age of 60. The risk adapted PSA screening intervals will be: (i) PSA < 1.5 ng/mL: screen every 5 years, (ii) PSA 1.5-2.99 ng/mL: screen every 2 years, and (iii) PSA ≥3.0 ng/mL: MRI and prostate biopsy, if biopsy negative, next PSA will be one year later.
Dr. Roobol then questions whether we should stop PSA screening at age >70? This is difficult since life expectancy isn’t easy to assess, and the harm/benefits are highly dependent on previous screening history. In her mind, this is clearly an opportunity for risk stratification. According to the EAU guidelines , for men 50-69 years of age, we should be offering early PSA in well informed men at elevated risk of prostate cancer: (i) men > 50 years of age, (ii) men >45 years of age and family history of prostate cancer, (iii) African-American men > 45 years of age, (iv) men with a PSA level > 1 ng/mL at 40 years of age, (v) men with a PSA level > 2ng/mL at 60 years of age.
(2) PSA result and then?
The EAU guidelines state that we should be offering a risk-adapted strategy based on the initial PSA, with intervals of two years for those initially at risk: (i) men with a PSA level > 1 ng/mL at 40 years of age, (ii) men with a PSA level > 2ng/mL at 60 years of age, and then postpone follow-up to eight years in those not at risk. According to Dr. Roobol, there are other specific notes regarding men age 50-59: (i) if the PSA level is <1 ng/mL, then men should see their doctor for the next PSA at age 60, (ii) if the PSA is between 1-3 ng/mL, then men should see their doctor for another PSA every 2-4 years, (iii) if the PSA is ≥3 ng/mL, then men should talk to their doctor about having a prostate biopsy. There are also specific notes regarding men age 60-70: (i) if the PSA level is < 1 ng/mL, then men should have no further screening, (ii) if the PSA level is between 1-3 ng/mL, then men should see their doctor for another PSA every 2-4 years, (iii) if the PSA ≥3 ng/mL, then men should talk to their doctor about having a prostate biopsy.
(3) Reflex Tests
Dr. Roobol is a proponent of reflex testing, particularly in men age 50-70 years of age whose PSA falls into the discussion about having a prostate biopsy. As we know, there are many tests available, including but not limited to PCA3, PHI, 4K-panel, Select-MDX, etc. This can assist in further delineating who is at risk of clinically significant prostate cancer.
In conclusion, Dr. Roobol notes a number of take-home messages: (i) screening can save lives and the PSA test is very useful as an initial risk stratification tool, (ii) stopping screening at low PSA levels is justified, (iii) an elevated PSA level alone should not trigger a biopsy, and (iv) reflex testing is strongly recommended.
Speaker: Monique Roobol, Erasmus University Medical Center, Rotterdam, The Netherlands
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the EAU - Update on Prostate Cancer – September 15-16, 2017 - Vienna, Austria
1. Tsodikov A, Gulati R, Heijnskijk EAM, et al. Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSCP and PLCO trials. Ann Intern Med 2017 Sep 5 [Epub ahead of print].
2. Vickers AJ, Ulmert D, Sjoberg DD, et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: Case control study. BMJ 2013;346:f2023.
3. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017;71(4):618-629.