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 yrs (arm A) with non-inferiority in terms of metastasis from PCa. 45 yrs old men 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%). Screening ends at age 60.
So far, a total of 30,298 men have been enrolled until October 2017 of which 15,152 were randomized into trial arm A. Most 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%) (Figure 1). 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 these 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%). Until now, 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). So far, 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. PCa detection rate was 37.5% (9/24) with 5 PCa having a Gleason pattern 4.
Figure 1 – Baseline PSA values:
In conclusion, the PROBASE trial started with a rapid recruitment and the expected distribution of risk-groups could be confirmed. The overall PCa incidence in 45 yrs old men is very low (0.16%). At a PSA threshold of 3.0 ng/ml the PCa detection rate is 35-40% with a high proportion of intermediate/high grade cancers (up to 70%).
Presented by: Christian Arsov, Düsseldorf, Germany
Co-Author: Nikolaus Becker, Heidelberg, Germany, Kathleen Herkommer, Jürgen Gschwend, Munich, Germany, Florian Imkamp, Markus Kuczyk, Hannover, Germany, Boris Hadaschik, Essen, Germany, Markus Hohenfellner, Heidelberg, Germany, Roswitha Siener, Glen Kristiansen, Bonn, Germany, Lars Schimmöller, Gerald Antoch, Peter Albers, Düsseldorf, Germany
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
Read more on the PROBASE Study from AUA 2018: Impact of Perceived Ambiguity and Other Psychological Factors on Previous Prostate Cancer Screening Behavior Among 45-year-old Men: Findings from the PROBASE-Study