EAU 2018: The German Risk-Adapted Prostate Cancer Screening Trial (PROBASE): First Results After Recruitment of 30,000 Men
The PROBASE trial is powered for superiority in terms of specificity of risk-adapted PSA screening starting at age 50 (Arm B) as compared to 45 years (Arm A) with non-inferiority in terms of metastasis from prostate cancer. Men that are 45 years old are randomly assigned to risk-adapted screening beginning at age 45 or five years later at age 50. Both groups receive risk-adapted PSA screening based on baseline PSA values: < 1.5 ng/ml (low risk) – 5-yearly PSA (expected 90%), 1.5-2.99 ng/ml (intermediate risk) – 2-yearly PSA (expected 7.5%), ≥3.0 ng/ml (high risk) MRI and combined systematic and MRI/TRUS fusion-guided biopsy recommended (expected 2.5%). In the trial, screening ends at age 60.
Up until October 2017, 30,298 men were enrolled, of which 15,152 were randomized into trial Arm A. The majority of the PSA values of trial Arm A were < 1.5 ng/ml (n=13,506, 89.1%), few in the range of 1.5 to 2.99 ng/ml (n=1,427, 9.4%), and at 3.0 ng/ml or above (n=219, 1.5%). In the latter group, a PSA value ≥3.0 ng/ml was confirmed by a second test in 115/219 subjects (52.5%, 0.8% of all trial Arm A participants). Median PSA of this subset of participants was 4.1 ng/ml (range 3.0-28.1). Subsequently, 81 subjects out of the 115 PSA-suspicious men underwent MRI (70.4%). PI-RADS v2 scores were as follows: PI-RADS 1 n=2 (2.5%) PI-RADS 2 n=32 (39.6%), PI-RADS 3 n=23 (28.4%), PI-RADS 4 n=16 (19.8%), PI-RADS 5 n=3 (3.7%). At this point, 81.5% (66/81) also underwent combined biopsy with a PCa detection rate of 33.3% (22/66). Thus, the overall PCa incidence in trial Arm A at the first screening round is 0.15%. The rate of cancers with a Gleason score of at least 3+4=7 was 68.2% (15/22). Currently, 561 participants initially assigned to the intermediate risk group underwent a second screening round two years later. Altogether, 6.6% (37/561) had a confirmed PSA increase ≥3.0 ng/ml (median 3.9, range 3.1-15.7). During this workup, 24 out of these 37 participants had an MRI with combined biopsy. In this group prostate cancer detection rate was 37.5% (9/24) with five patients having a Gleason pattern 4 prostate cancer.
In summary, the PROBASE trial started with a rapid recruitment and the expected distribution of risk-groups could be confirmed. The overall prostate cancer incidence in men 45 years old is very low (<1%). Increased PSA levels should be confirmed before performing prostate biopsy. However, men with a confirmed baseline PSA ≥3.0 ng/ml or those initially assigned to the intermediate risk group and exceeding the biopsy cut off two years later have a high risk of harboring significant prostate.
Presented by: Christian Arsov, University of Dusseldorf, Dusseldorf, Germany
Co-Authors: Becker N, Herkommer K, Gschwend J, Imkamp F, Kuczyk M, Hadaschik B, Hohenfellner M, Siener R, Kristiansen G, Schimmöller L, Antoch G, Albers P
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, twitter: @zklaassen_md at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark