Tom McNicholas has written widely on many aspects of urinary disease. He is particularly in demand for teaching on benign prostatic disease and urinary symptoms. He has major interests in the management of prostate cancer, the treatment of urinary stone disease and in making common urological investigations (especially prostatic biopsy) both painless and safer.
He has written over 150 major scientific papers which can be reviewed in the bibliography. Most recently he has been lead author of the chapter on Benign Prostatic Disease in the latest addition of Campbell’s Urology. This 4 volume textbook is the “bible” for urology and is used by urological experts worldwide. He is one of only a small handful of British urologists to have been recognised in this way.

The use of Pro2 PSA with particular reference to men younger than 60 as presented by Tom McNicholas at the AUA Meeting in San Diego, California on 7 May 2013

Prof.Tom McNicholas
Uncritical use of the standard prostate blood test PSA leads men to have unnecessary biopsies and to over diagnosis and usually over treatment of prostate cancer in many men who may never otherwise have suffered significantly from their cancer.  Nevertheless some prostate cancers are lethal and need to be detected.
Therefore, we have explored whether we can we improve the situation by using new markers (blood tests) such as the Pro2 PSA (“p2PSA”) and its derivatives, especially the “prostate health index” or PHI?
Using an unrestricted educational grant from Beckman Coulter Inc we set up a real world study in 5 European Cancer Centres (Milan, Spain, France, Germany and the Lister, Stevenage in the UK).  We recruited men from our clinics who were being worked up for prostatic biopsy to see if they had prostate cancer.  There were no particular restrictions.  It was normal clinical practice in each of those centres.  We took blood from the men just before biopsy and measured the standard tests already available and widely used (PSA, free PSA) and the new markers (p2PSA, PHI) and then compared them in terms of accuracy of prediction of prostate cancer and perhaps more interestingly looked at the data to see if we could use these new markers to predict who could be safely not biopsied.

There are over a 1000 men in the whole study and there are 646 men who were reported in Milan at the EAU who have a PSA between 2 and 10 and whose outcomes we have in the database.  238 of these men were below the age of 60 years and that is the particular focus of this discussion. 

The data suggests that the new markers were indeed more accurate than the existing markers, especially the percentage p2PSA and the PHI.  The statistical processes (ROC curves) show an improvement in accuracy (though some authorities such as Andrew Vickers do not really think these mean much and it may be worth discussing the significance of all these graphs etc with him at some point).

The data suggests that the new markers are more accurate in predicting the presence of prostate cancer in the biopsies. Furthermore, it appears that we could use these new markers to choose who not to biopsy and that would obviously be an advantage for those men in particular, but for the health care system economically as well. 

If we use a standardised cut off with the values for sensitivity set at 90% we therefore accept that we will miss 10% of the cancers in the population, but it is important to know what  type of cancers are being missed and their nature and how dangerous they might be.  PHI in particular indicated that the missed cancers (26 in all) were not the most dangerous cancers (which are scored according to the Gleason scoring system as 8 or 9 on a range of 2-10) and the Gleason 7 cases were mainly Gleason 3 + 4 rather than 4 + 3.  23 of the 26 were in fact much less dangerous Gleason 6 (or 3+3)  cancers.

If we make the cut points more helpful overall by setting them at the best balance between sensitivity and specificity, this means that we could potentially save many more biopsies (up to 60%), but we will also miss more cancers.  Here again, it is important to know how bad these cancers might be that we might miss.  The PHI cut offs in particular showed that we did not miss any Gleason 8 or 9 cancers in this group of younger men, which is reassuring.  In fact, this data is also true of the larger population of men with PSA between 2 and 10, but percentage p2PSA did miss one cancer with a Gleason 9, though on enquiry this man had violated the entry criteria and presented with a PSA of 4000, which may have been mistakenly read as 4 during the data collection.  His percentage p2 PSA was below the cut off and he was missed, but in fact he was caught by the PHI, so would not have been missed using both markers which we recommend.

In conclusion these new markers (p2PSA and its derivatives especially the PHI do suggest an increased accuracy of prediction of the presence of cancer in biopsies versus standard tests (PSA and free PSA).

These markers could be used to identify men who could avoid biopsy.

Whilst this is true of the overall population of men with a PSA between 2 and 10 it seems to be more strongly the case for this younger cohort of men suggesting increased value in this group of younger patients.

A longer version of this presentation incorporating the overall population and the men aged below 60 won us a prize for best poster in the session in the EAU Meeting in Milan in March 2013.

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