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ERSPC trial affirm the benefits of prostate cancer screening

Updated results of the ERSPC trial affirm the benefits of prostate cancer screening in reducing death but open opportunities for new screening tools.

August 2014: By Vincent J Gnanapragasam
Addenbrookes Hospital, Cambridge

The recent publication of the updated European Randomized study of Screening for Prostate Cancer trial has again ignited the debate on the benefits of screening for prostate cancer. What we can clearly say is that a screening programme does reduce mortality from prostate cancer.

Schroder and colleagues in their 2014 update have demonstrated that with longer follow up these benefits are becoming more apparent. At 13 years the absolute risk reduction is 21%. Conversely however, the numbers needed to screen remain high at 781 to save 1 life. Sixty percent of the detected cancers were also of low-risk and will probably not cause any harm in a man’s natural life span. While screening itself therefore does appear beneficial, the critical issue is the tool by which it should be done. Serum PSA at a threshold of 3ng/ml is clearly not the ideal tool for a population based approach.

Recent advances have identified new diagnostic assays that have greater sensitivity and specificity for cancer detection and the potential of harbouring clinically significant disease. These assays exploit different PSA isoforms and other kallikreins to produce composite scores that appear to be better able to predict both the presence and aggressiveness of a cancer. One very good example of this is ProstateCheck which includes total PSA, free PSA, intact PSA, and kallikrein-related peptidase 2. In a sub-cohort group of the ERSPC study, use of ProstateCheck demonstrated an improved ability in detecting the presence of cancer compared to PSA alone. In a further study in 2013 ProstateCheck was also better able to predict the presence of aggressive cancers compared to standard clinical parameters. Use of such an assay instead of just a PSA test thus has the potential to both reduce unnecessary biopsies and also increase the detection of clinically significant cancers. This test is currently available in the UK through ProstateHealth UK. Genetic research has further revealed sub-populations of men with high inherent susceptibility for developing aggressive disease and who would be an ideal population for targeted screening. These advances are just starting to make their way into clinical practice. There is an urgent need for NICE and the National screening board to consider a structured approach to testing these as potential screening tools in the UK, either as integrated tool or using a multi-tiered approach. Any new screening studies will also have to work within the paradigm shift which is happening in prostate cancer diagnostics with the introduction of image guided and targeted biopsies of tumours. This is already resulting in many fewer missed and wrongly characterised cancers.

The ERSPC study has shown that screening can undoubtedly reduce cancer death and this argument is answered. The new question now is how to maintain or improve this benefit but with better tools that can reduce over-diagnosis. This is the exciting new space for prostate cancer screening research.

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