JU INSIGHT: Prostate-specific Antigen and Biopsy Contamination in the Goteborg-1 Randomized, Population-based, Prostate Cancer Screening Trial
By: K. Stinesen Kollberg, PhD; E. Holmberg, PhD; A. Josefsson, MD, PhD; J. Hugosson, MD, PhD; R. Arnsrud Godtman, MD, PhD | Posted on: 01 Nov 2022
Stinesen Kollberg K, Holmberg E, Josefsson A, Hugosson J, Arnsrud Godtman R. Prostate-specific antigen and biopsy contamination in the Göteborg-1 randomized, population-based, prostate cancer screening trial. J Urol. 2022;208(5):1018-1027.
Study Need and Importance
The Göteborg randomized, population-based prostate cancer (PC) screening trial is one of few studies that has demonstrated that organized prostate-specific antigen (PSA) screening significantly reduces PC mortality. Even when a screening study has demonstrated a mortality reduction, the degree of pre-testing and contamination is of importance as it can dilute the “true” effect of screening. In light of the problem with overdiagnosis and overtreatment, summarized evidence suggests that the benefits of organized PSA screening do not clearly outweigh the harm on a population. This article describes the level of pre-testing and contamination in the Göteborg-1 PC screening trial. A total of 20,000 men, 50-64 years old, were invited in 1994 and randomized to either a screening group (SG; offered PSA testing every 2 years) or to a control group (CG). Follow-up was through December 31, 2014.
What We Found
There was an extensive degree of contamination with similar proportions of men being PSA-tested in both groups (see Figure). During follow-up, 72% in the CG took at least 1 PSA test (contamination) compared to 87% of men in the SG. Of all PSAs, 24% in the SG and 39% in the CG were above PSA threshold (≥3 ng/ml). In the SG, 93% of the men underwent prostate biopsy within 12 months from a raised screening PSA whereas a mere 28% moved on to biopsy in the CG.
We were unable to distinguish PSA screening in the asymptomatic setting from tests taken as part of diagnostic workup. Since mild lower urinary tract symptoms are fairly common in this age group, it is likely that a proportion of the contamination is generated as a result of symptoms. We do not have information from all private laboratories (1 laboratory missing) and PSA and pathology data were not available for the entire follow-up period for all laboratories and pathology clinics.
Interpretation for Patient Care
Similar proportions of men were PSA-tested in both the SG and CG, yet only a minority of contamination PSAs led to biopsy. Also, men in the SG started screening at a younger age. These could both be explanations for our result that organized screening is more effective in reducing prostate cancer mortality than non-organized testing. When carried out properly and compared to an unscreened population, the effects of organized screening are likely even greater than previously shown in the Göteborg-1 PC screening trial.