Single intensive screening intervention using PSA and Stockholm3 in combination might reduce prostate cancer mortality

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Published: 16 Mar 2023
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Prof Peter Albers - Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

Prof Peter Albers speaks to ecancer about the interim analysis of mortality results after 6.5 years of follow-up of the Stockholm3 prostate cancer screening trial (STHLM3).

Prof Albers says that the STHLM3 trial utilised a single prostate-specific antigen (PSA) and Stockholm3 test to identify Gleason score ≥7 prostate cancer. In this follow-up prostate cancer specific and all-cause mortality in men invited to STHLM3 to men not invited was compared.

The results from this study might suggest a potential effect on reducing prostate cancer mortality by a single intensive screening intervention using PSA and Stockholm3 in combination, to the cost of increasing prostate cancer incidence.

Prof Albers concludes by discussing the impact of these results on clinical practice.

The Stockholm study is a study that had been published initially in 2015 developing a new test algorithm combining PSA with several other parameters, including genetic scoring, genotyping, they used PSA subtypes in addition to clinical parameters, in order to form a combination score and they called it the Stockholm3 score. The reason to develop this score is that we have to work on the specificity of PSA because if we use PSA alone as a test we have shown that in the ESPC trial you could achieve a 20% reduction in prostate cancer specific mortality, however, a lot of men have to be screened, have to be diagnosed. So PSA needs to be further developed and this was actually the reason to perform this trial, followed by another trial, also in Gothenburg and around the world to actually elude on these questions. 

The study design was they questioned the registries in Sweden, in the area around Stockholm, and then they either invited or non-invited men in the age group 50-70. The rough numbers are that they have about 70,000 men that were not invited and from the invited ones 35% accepted to have a PSA and a Stockholm3. Only if PSA was above 3 or the Stockholm test was above the cut-off, and this was 11%, then they underwent MRI and biopsy.

The group around Henrik Grönberg and Tobias Nordström and a lot of other investigators from the Karolinska Group, they report now the 6.5 years mortality data compared of these Stockholm3 test algorithm to the non-invited participants in terms of prostate cancers detected and prostate cancer specific mortality. They found that the mortality was really reduced, considerably reduced using this test algorithm, which means that PSA and Stockholm3 together work very well in lowering the number of men that are unnecessarily undergoing biopsies. 

The problem of this study, and I don’t have a good answer for this question, is why only 35% of men have accepted to be tested with this new algorithm. So everything we do in screening needs to be explained to the population so that ideally 100% of men would accept this new test. This is very important, that we work on this. 

But the final result is with Stockholm3 you obviously can improve the specificity of PSA so less biopsies are undertaken in men that don’t need it. There is a question of cost – how costly is this if you do this for a population base? Because in Norway they have performed a cost effectiveness analysis, PSA against Stockholm3 because Stockholm3 more or less integrates PSA. The cost difference is tremendous – twenty times higher than the PSA test. So all this has to be further developed. If you decrease the number of diagnoses and treatments, this would compensate for higher initial costs. So the idea to work on better algorithms than PSA was perfect but we’re not at the end of the road; the problem is not solved.