Fritz H. Schroder

How to improve duration and quality of life in men?

Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine’s ‘Spotlight on Prostate Cancer’ article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world’s key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts’ views and give their own personal opinions on PSA screening.

Screening for prostate cancer by use of serum prostate specific antigen (PSA) remains controversial. In the recent Cochrane analysis, an attempt is made to clarify the issue by conducting a meta analysis of available randomized screening trials. Two large trials are considered to provide data of similar and sufficient quality to conduct a separate meta analysis. However, in the view of this author, this analysis fails because standard Cochrand quality criteria are not observed. Details are given and the outcome suggests that one of the trials, the European Randomized Study of Screening for Prostate Cancer (ERSPC) should be considered superior to the Prostate, Lung, Colon, Ovary screening trial (PLCO) conducted in the USA.

The “European Randomized Study of Screening for Prostate Cancer” (ERSPC) was initiated in 1993 and up to 1998 six other European countries were joined. The main goal is to establish the effect of Prostate Specific Antigen (PSA)-based screening on prostate cancer (PCa) mortality with morbidity as secondary end point. At present, with 11 and 12 years of follow-up significant relative reductions of 21 % and 31 % relating to both end points have been reported. The diagnosis of non-life threatening PCA (over diagnosis) is estimated to be in the range of 50 % and represents the main “harm”, which prevents the introduction of population-based screening. As a result, the prevention of over diagnosis is now given top research priority. PSA as a screening test has poor performance characteristics including a low specificity. With the cut-off value of 3.0 ng/ml chosen within ERSPC, about 25 % of men aged 55--69 test positively, 75 % have “negative” test results, which do not definitely exclude the presence of PCa. Research to establish empirical schemes of follow-up based on PSA levels and other parameters are ongoing worldwide. In the meantime, we are, by approximation, capable to identify over diagnosed PCa detected by screening. Active surveillance can be applied to avoid side effects and expenses of treatment and is, among others, based on the grade of differentiation determined on biopsies. The assignment of the most favorable “Gleason score 6” is a crucial decision element. Unfortunately, biopsy pathology underestimates the true degree of PC aggressiveness by 25--30 % which establishes the need of careful follow-up.