My return to the game of tennis took place at the men’s morning session of my local club. As we relaxed afterwards, the conversation quickly moved from “welcome back” to “are you still working in X hospital?” to the usual “what does a scientist in a hospital actually do?” and then, inevitably, to prostate-specific antigen (PSA) testing.
The conversation at the tennis club about prostate cancer and PSA mirrored conversations I’ve had many, many times. When I express reservations about randomly doing a PSA test, the essence of the responses I get is that PSA is "just a test", and why wouldn’t you do it?
If it’s positive, you have cancer and while that’s not good at least you can go and get it treated early. If it’s negative, sure you know you have nothing to worry about. To which I respond – Nice idea, but…
For most people a test is something that tells you yes or no; maybe doesn’t come into it. Trouble is, for asymptomatic men, a PSA test is more likely to produce a “maybe” than a yes or no. And “maybe” leads to doubt and anxiety that may never really go away. And maybe often leads to invasive follow-up testing.
And “maybe” can lead to morbidity as a result of this follow-up invasive testing. Of course “maybe” can lead to a diagnosis of cancer, but that cancer might not have been worth treating at all.
Is PSA worth testing then? I was fortunate recently to have Prof Joe Duffy give a lecture to our FRCPath trainees meeting. Prof Duffy is a biochemist who is recognised internationally as an expert in this area, and was also the principal author of the Association of Clinical Biochemists in Ireland tumour marker guidelines (Duffy & McGing, www.acbi.ie).
In his talk Prof Duffy outlined the pros and cons of PSA as a screening tool for prostate cancer (PCa). On the face of it, there does appear to be considerable advantages. It is the most sensitive non-invasive test for PCa.
The vast majority of cancers detected following PSA screening are organ-confined. Use of PSA has the potential to detect PCa up to 10 years before there is clinical evidence of disease. Additionally prostate cancers detected with PSA screening have lower stage and are more differentiated than those that might be detected if PSA was not carried out. Sounds great! So why the concern?
For anything to be worthwhile the benefits have to outweigh the risks. The worry about PSA is that the benefits outlined above are strong and well vocalised but you need to know the negatives. It is important that the patient is aware of these negatives in order to make an informed decision.
Recently a relative was having an angiogram. Before that procedure he received a booklet telling him about the scan. Importantly, it included details of what might happen as follow-up (including angioplasty) if an abnormality was detected. Doing PSA should be regarded similarly, not as a “simple test”, but as a procedure with potentially serious consequences.
Though the risk of serious consequences is low, such consequences do occur, and patients have a right to know this before they have a PSA test done.
So what do we need in order to assess the overall risk to benefit ratio? Returning to Prof Duffy’s lecture, he told us that PSA screening is controversial because of the absence of properly executed randomised trials (level 1 evidence studies) comparing patient outcome and quality of life in screened and control groups. In order to determine whether PSA screening is beneficial or not, a trial would require approximately 200,000 men and a time period of 10 years.
Following publication of their interim results in the New England Journal of Medicine (NEJM) last March, you will all know that two such trials are in progress, one in Europe and the other in the US – the European Randomised Screening for Prostate Cancer (ERSPC) trial and the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) trial. By the end of 2001 over 215,000 subjects had been randomised. Final results are expected in 2011.
That means we should know the risks versus benefits in 2011, but not before that (as was clear from interim results).
The NEJM editorial which accompanied the two interim-results papers stated: “Serial PSA screening has at best a modest effect on prostate-cancer mortality during the first decade of follow-up. This benefit comes at the cost of substantial overdiagnosis and overtreatment. It is important to remember that the key question is not whether PSA screening is effective but whether it does more good than harm.”
The editorial then goes on to discuss the trade offs between benefit and harm for PSA screening. It concludes: “Some well-informed clinicians and patients will still see these trade-offs as favourable; others will see them as unfavourable. As a result, a shared decision-making approach to PSA screening, as recommended by most guidelines, seems more appropriate than ever.”
In my personal life I have met many men who have expressed interest in PSA testing, some of whom have had regular PSA tests as part of annual “health screens”. However, I have not yet met any member of the public who understood the possible repercussions of a raised PSA level in an individual without prostate cancer, or the lack of reassurance to be derived from a “normal” result.
PSA is a very useful test, when applied appropriately. But doctors should not push it; nor should they order PSA just because a patient asks for it. If you do order a PSA test on an asymptomatic man, remember the recommendations on shared care. Take the time to inform him of the pros and cons, of how PSA usually can not rule out cancer and how it may lead to follow-up testing with unpleasant or nasty consequences.
In fairness, very many GPs do order PSAs appropriately. But for those who are not so careful, please think of the patient – you are the professional and you know a lab test does not give a simple yes or no. It is your responsibility.
Dr Peadar McGing is a Principal Biochemist in a major Dublin hospital
