A Letter from the President of BAUS to the Daily Telegraph

Very sensible comments from BAUS President. This daft headline and misleading comments in a major paper (https://www.telegraph.co.uk/health/healthnews/10121870/Half-of-prostate-cancer-cases-may-be-missed.html) caused reaction not only in the UK but also around the world, including Australia where I dealt with enquiries from patients and health correspondents alike. The tone of the comments contained would lead patients to believe that outside a “handful of hospitals”, that patients are being managed inappropriately by not having an MRI before a decision is taken regarding a biopsy (or to guide a biopsy).
This remains a very interesting research area and the group at UCL are leading here. However, it is certainly appropriate for the BAUS President to remind people of the current status and to reassure clinicians and the general public that the current standard is not MRI for all with a raised PSA. I am equally impressed and disappointed on a weekly basis by the results I see using 3T mpMRI – we have a way to go yet before this expensive modality finds its place in routine practice.

Laura Donnelly’s article in Saturday’s Telegraph is most unhelpful.
Sadly, it is only likely to spread further alarm and despondency among patient’s and clinicians about the diagnosis of prostate cancer. While we support the view that MRI can be useful in targeting lesions in the gland that may require biopsy, we are certainly not yet in a position to implement the practice across the UK, nor is there evidence yet that we should do so. In an recently published comment for the BJUI (https://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2012.11779.x/full) we discussed the changing paradigm for the evaluation of a raised PSA and discuss the implications of the more widespread use of multiparametric MRI, in terms of cost, availability of 3 Tesla scanners and critically expertise in the interpretation of these complex images. Simplistic and alarmist articles in national newspapers are not the best way to achieve changes that result in an eventual benefit to patient care.

Whilst agreeing with comments above I would remind everyone that in typical ‘good’ journalistic style the article was placed at the top of the front page of the Telegraph and has sparked all this comment. The final paragraph of the article was positioned away on page 2 and included the more balanced and conciliatory paragraph below. ‘She said: “This early data suggests that giving men an MRI scan before a biopsy may put clinicians in a better position to tailor investigations and treatments further down the line. However further research is necessary before we will know the true value of this method.”’

There are a number of questions that need to be answered about prostate MRI, and challenges for the development of an approach to prostate cancer diagnosis that will detect those cancers that need treating, and leave undiagnosed that which don’t pose a threat to health or life expectancy.

1. What is the positive predictive value of MRI? On current data, either before first or subsequent biopsy and taking’ all comers’ it is around 66%. If you use a scoring system like PIRADS and subdivide it into those with an equivocal score (3) and those with a higher risk score (4/5) and look at all cancer then you have about 50% and 80%+ PPVs respectively. If you try to apply some sort of threshold for clinical significance then those figures change.

2. What is the negative predictive value? A high NPV would mean we could use MRI to allow some men to avoid biopsy. I think this is easier in the older man with a large BPH prostate where the higher grade lesions show up as discrete lesions, and the PSA density is low, than the younger man whose MRI is more difficult to interpret, and diffuse change in the PZ can hide tumour.

As well as the performance characteristics of the test there are other factors to consider – would adding in MRI to the diagnostic pathway actually reduce the numbers of men biopsied, or would it just be an additional test to add to the expense of a diagnosis of PCa? What proportion of men ‘should ‘ test positive on MRI? In cervical screening the screeners are checked for ‘compliance’ with expected rates of positive tests and if they are far away form the average their work is checked to see whether it reflects different disease prevalence, or a tendency to ‘overcall’ or ‘undercall’.

There is a suggestion that in some practices a radiologist is unwilling to score a 1-2 if they think a man will not get a biopsy as a result. If that means that many are scored equivocal ‘just in case’ then adding MRI would not result in any greater efficiency but would only add to burden and cost.

MRI will not detect all cancer, and will not detect all of the clinically significant cancer – no test is perfect. The question, to my mind, is – is it better than what we have now (standard TRUS)? Who would it be most useful in – men with a borderline biopsy indication? Those at high risk (eg family history)? Those with a negative biopsy and a persistent indication eg rising PSA?

What is the best way to target a lesion on MRI? Software assistance, cognitive registration , in bore targeting? Is a transperineal & GA necessary or can most lesions be targeted using TRUS, once the area of a higher probability of cancer is known?

Ultimately, as evidence to answer these questions accumulates, we will need to consider how to control the use of MRI. Already a number of hospitals in the UK have MRI before biopsy for selected patients – if we can collect data on this, and assess how/if it changes biopsy practice then we will be in a position to assess its usefulness in UK practice. And, if it is useful outside of few highly specialist centres then we would need to address issues of capacity, training and access at that point.

I saw a draft of the BAUS Presidents letter and fully support everything it says. And as Mark Speakman points out, the only third-party comment the DT reporter obtained was from Kate Holmes of Proster Cancer UK, who added a cautionary tone about further research being required, which was unfortunately hidden at the bottom of the article on page 2 of the broadsheet. I believe a very few urologists are reassuring men with normal MRI that they don’t need a biopsy, but hopefully within a research clinic and perhaps repeating MRI as well as PSA on them at intervals. I agree with the UCLH team and others that this is coming, pending the PROMIS trial. I hope the radiological community is preparing for this influx of new work. But for now a realistic position must be stated: the UK in general terms is not ready yet.. not trained & not funded. The big issue I have with this DT article is that it undermines what the health service can currently offer. This will cause frustration and friction between patients and their doctors.

The construct of this debate is illustrative of the challenges of bringing novel ideas to routine practice. Early in cycle of a novel test, its use is clearly experimental and outside of clinical practice. After rigorous study showing a benefit of a novel test and its inclusion in clinical guidelines, then not using it along such guidelines may be sub-standard care. The challenge is this “grey zone” period where we have some data and experience, but not definitive. Its hard to determine if its sub-standard to use it versus wait for more data, and who decides when the evidence is officially “definitive.” As Prof. Dasgupta says–he would consider using and MRI before biopsy, but at this point I can neither fault him for doing that or not doing that.

I have just used this blog – to great effect I think – to introduce a panel discussion with the title, ‘Which men should be getting an MRI before biopsy?’ at a meeting in New York organised by Herb Lepor. The audience was particularly taken by the comments made on New York practice. I think it is fair to say that most of the well known units (MSKCC, NYU, Cornell) are offering high quality pre-biopsy MRI (or more correctly post-biopsy) as most consultations are the second, third or sixth opinion in many. Adoption in the USA is happening, largely led by academic centres, but this of course should not influence us.

There are, I believe, three dimensions to the discussion: a moral one; one based on evidence and one that relates to issue of access. I shall leave the moral issue until later but it may prove to be the one that drives change.

Much of the evidence has been summarised and commented upon by earlier bloggers. There are two errors that we can make in relation to adoption – to be too early or too late. Much of the concern has focused on the first of these errors. This is quite a reasonable position. However, when we adopt this position we should recognise that we become vulnerable to the second error. The second error should not be taken lightly given that one million prostate biopsies are performed each year in the EU alone, many more in the USA. Lets assume that about half of these are probably unnecessary, and therefore better avoided – in that these men will either have no disease or harbour truly low risk disease with nothing more than micro-focal Gleason 3 plus 3. Lets assume for a moment that the NPV of MRI is a 95% for clinically significant disease – a figure that has been arrived at in a large number of studies. Lets assume that the MRI is reported as ‘normal’ in about 30% of patients. It follows that if this is the case about one third of a million men per year might reasonably avoid a procedure that is uncomfortable, increasingly dangerous (Meropenem resistant plasmids were identified in India 6 months ago) and may confer a diagnosis that is associated with limited utility and possible harm (low risk prostate cancer). MRI would also increase the proportion of men with clinically significant disease that are correctly identified and risk-stratified. For this we have a systematic review as evidence and another 1000 patients reported in the literature since that review was published in January 2013. This space is not a static one.

When people have looked back on the rate of adoption of thrombolysis in the management of CVA the general consensus is that it was adopted too late, given that several RCTs (diagnostic studies do not require RCTs to generate level 1 evidence) had shown time and time again that disability and death were reduced by offering victims of stroke early intervention. Instead of adoption, the response was always ‘one more trial’. Indeed, as a result of this observation several commentators have calculated the number of lives lost and the years of life compromised by not adopting the technology earlier. It makes difficult reading. Indeed, it is humbling to note that full adoption in the UK required government intervention.

In relation to the issue of access I believe that urologists have an important role. All things in medicine have to be done well. The driver for improvement usually comes from someone asking for something better. If an MRI has movement artefact at UCLH we get another one. If the MRI quality is compromised by biopsy artefact (something that can last 6 months), we get a repeat scan in 6 months. This is no different to the quality control standards that we apply in other areas of urology. The important thing is that we, as urologists, are probably the group best placed to drive this process. The passive stance of ‘we have no resource’ is going to be hard for many outside observers to accept given how successful many groups have been in finding resources (often from charitable sources) for an equally expensive capital investment (Da Vinci robot) at a time when most of the literature was pointing to no more than equivalence.

The moral or ethical dimension is proving more and more interesting. Some of the bloggers have indicated that they themselves would probably insist on an MRI prior to a biopsy. Of note Roger and Damien in their excellent and brave newspaper piece on their own diagnoses both stated quite emphatically that they chose imaging prior to the biopsy. Indeed most urologists now hold this position. Who would not, as there is little obvious downside? This does create the dilemma that professionals may have views on their own care that is discordant with the care or advice that they offer their own patients. This is a position that is clearly not sustainable.