Prof Noel Clarke – Salford Royal NHS Foundation Trust, Salford, UK
Prof Hardev Pandha – University of Surrey, Guildford, UK
Prof Amit Bahl – University Hospitals Bristol, Bristol, UK
Dr Nina Tunariu – The Royal Marsden Hospital, London, UK
NC: Welcome to Frankfurt. We’re here at the PROSCA 2018 conference discussing elements of prostate cancer relating to diagnosis, treatment in early stages, treatment in intermediate stages and later stage disease. I’m joined by three of my esteemed colleagues from the UK, Amit Bahl from Bristol, clinical oncologist, Nina Tunariu, a radiologist from the Royal Marsden in London and Hardev Pandha, medical oncologist from Guildford. I’m Noel Clarke, I’m a urologist with a specialist interest in oncology from Manchester at the Christie Hospital. So I’m going to start by opening up with the early stage disease, Nina, and you being an expert in imaging. We’ve had quite a discussion about imaging of the primary disease, prognostication diagnostics, tell us what you’ve taken from PROSCA 2018 in relation to MR imaging of the prostate in the diagnostic setting.
NT: Well I was happy to see that, indeed, people have taken on board the latest data and the multiparametric MRI seems to be now a recognised tool and people are keen to use it in diagnosing prostate cancer. I have also been happy to see that we understand the limitations of multiparametric MRI prostate and it seems that the best way forward is, indeed, a combination of a multiparametric prostate with targeted and standard biopsies. By all means we talked about some additional tests which may take these techniques and this combination further but for the time being it seems that these two approaches – combining multiparametric MRI and biopsy – is the way forward.
NC: And this is at variance with some of the messages we get from the UK alone, isn’t it, where there is a push to get rid of the biopsy, something which has been quite controversial. But here there’s been a realisation and, indeed, some quite vocal expression that the biopsy is critical. What’s your view of that?
NT: I will agree, no matter how much I would like to say, ‘Let’s just use only MRI,’ I think we need to keep going and combining because there is no 100% test. But I do think the future is, as I said in my talk, fewer biopsies but in a wiser system.
NC: Amit, if I might come to you. Patients who have been biopsied, we had a very good discussion and some keynote lectures on biomarkers and prognostication and prediction – gene testing and so on. What was your view of Chris Evans’ talk in the biomarker prediction for prognosis and treatment stratification?
AB: Well it was a fascinating talk but I think what we need to be sure about is realising what the clinical implications are. We need to go back to the real basics as to what we are trying to address here. Some of the biomarkers which have been talked about regarding whether one can go into a surveillance strategy or one would need to be treated for prostate cancer were being done instead of doing an MRI scan for staging that prostate cancer which actually, from UK practice, I find slightly strange because I would do an MRI and I would direct things on biopsy based on that MRI, whether you collect targeted or saturation or transperineal biopsy and then consider the options regarding whether the patient goes for surveillance or not. They are here to stay because they do have some evidence, however retrospective that may be, or might not have analysed the whole prostate in its totality. It’s probably an additional tool when you’re facing an individual who is finding it difficult to make a decision as to whether to choose a radical option with the potential side effects or whether you can adopt an active surveillance strategy in that individual, so maybe in that setting. Maybe also in the salvage setting and that is where I see it as a bigger role because it’s almost learning from breast cancer with the Oncotype-DX and how to refine the results of that to try and avoid systemic therapy in the majority of the ladies with breast cancer, as we’ve just recently seen. Now, will prostate cancer be able to go that step forward? That’s my aim, that’s my hope. But we still need to remember the basics like MRI scan and basing our decisions on biopsy and multidisciplinary discussions.
NC: And, as you said, I’ll come to you in a minute Hardev, we’ve got some interesting questions that I want to you address in relation to genomics and things, but in relation to the use of these tests in the US and Europe there really is a big difference isn’t there?
AB: It’s a complete difference, so in the US, as I understood it, because multiparametric MRI is not reimbursed in the system whereas these tests are. It seems a little bit bizarre to me that you can’t do a basic test which has been proven in trials and therefore these are being used. And if these are negative or are showing you a higher risk score then they can justify an MRI scan. I would have gone the other way around. So there is a big discrepancy and maybe it is time to collect data across the Atlantic and see whether it results in differing strategies and, of course, we wouldn’t know the results but at least we can get active surveillance strategies across and see.
NC: Yes, that would be an interesting concept because surveillance really is not uniform, it’s something I’ll come back to in a minute. Hardev, there was a state of the art talk by Rob Bristow about genomic risks and family risks. Should we be doing genomic tests on all the patients or some of the patients or none of the patients?
HP: The scale of that undertaking, compared to the very small percentage of patients which this would include as a very high risk group is obviously very small. So, firstly, something very simple and clinical, which is a good clinical history, a family history and outlining what it means to have a positive family history rather than, for example, a patient having a father who died in his late 80s of prostate cancer versus somebody being diagnosed in their 60s and then having a brother and one other blood relative, that’s the common sense context first. So that would reduce the numbers considerably but, at the same time, to expand that to look at family history of ovarian cancer, of breast cancer and really widen that perspective, so I think that’s important.
NC: And that’s a really critical point, isn’t it, because not only is this a disease affecting men, which clearly it is, prostate, but it is associated with that crossover, certainly with breast cancer and the BRCA related genes.
HP: Absolutely and we know the biology of the BRCA mutation and its biological consequences and drugs that may be potentially useful. So it’s a very specific and very important group to identify, absolutely.
NC: So, Nina, could I ask you about this surveillance thing and MR scanning? Because we are a bit mixed, aren’t we, in how we’re doing things. Some people scan every six months, some people just do PSA, some people do repeat biopsies. Where does MR sit with that and how good is it at surveillance?
NT: I think that I would like to say that I’m biased. The MRI will be a good test but, and we have this conversation all the time, we do need to work towards a quality control. That’s where people have this discrepancy in their attitude because if you have a centre in which the protocol is very accurate, your radiologists are heavily trained, they do a high number of cases, then, of course, that centre will be more trusting in MRI. You have a centre in which maybe the diffusion weighted imaging, which is the cornerstone of the protocol, is not good enough then in those centres you, as a clinician, may lose a bit your trust. So, to me, in order to uniformalise that’s what we need to do – quality control of the MRI.
NC: And it’s interesting in the PROMISE trial, what people tend to ignore in those results is they started off with ten centres, all of them were quality controlled, all of them had special training, they rejected three and came down, I think, to seven, it might even have been six. So quality control is absolutely critical.
NT: Yes, for MRI specifically.
NC: Let me move on to the more advanced element of this. Firstly PSA failure, just a couple of minutes on this, Amit, because we had a good session, went a step in with what when people fail after radical local treatment. What did we learn from that?
AB: The interesting thing is that we have to deal with the situation as to whether it’s a failure post-radical prostatectomy or a failure post-radical radiotherapy. Clearly, the idea is whether we are trying to find salvage treatment options, so is there the role for radiotherapy to the prostate bed and the pelvic lymph nodes, or should we be actually chasing oligometastatic disease and then treating the oligometastatic disease, whether we treat it once, twice, n number of times. That is going to be a very continuous debated point over the next few years because some people are slightly withdrawing from the idea of prostate bed radiotherapy because we know that results in the literature, by and large, show radiotherapy being effective 50% of the time. Now, radiotherapy in primary prostate cancers, in early localised prostate cancer, is effective 90% plus of the time. So that is not the failure of radiotherapy, it’s the failure of targeting the right place for radiotherapy. And that is where imaging will come into play but that, again, is the big dilemma – what imaging do you go with? The other thing to remember is that the kneejerk reaction that the PSA just goes above 0.2 and I need to do a choline PET scan when the sensitivity of choline PET is very low below PSAs of 0.5 and, some would argue, even 1.0 and even the PSMA is better but it’s not a fool-proof test. So it is always understanding what your imaging is going to give you and what that will guide your treatment strategy as.
NC: I think that session really highlighted the lack of good quality evidence as to what to do. There was genuine confusion but with a view that treatment should be reserved, systemic treatment should be reserved, for a relatively small number. Now just finally, Amit, you gave a terrific lecture on sequencing, really enjoyable.
AB: Thank you. It’s not very usual of you to praise me like that but I’m happy for it.
NC: Most unusual. But I’m going to ask Hardev’s view of this, which is the sequencing. Now, one thing that struck me with Amit’s talk was this notion that we’re not giving docetaxel early enough and we should give it right up front. What do you think of that?
HP: I think Amit made quite a compelling argument and the reluctance to bring it in very early is very much based on perceived patient preference more and more, and clinician preference. There’s been this sense of relief at not having to give chemotherapy which Amit addressed pretty much head on. It is something really for us to look at. We talked about potential toxicity and neutropenic issues and casualty secondary to docetaxel in one of the other talks and, certainly in our collective experience, docetaxel is quite a straightforward treatment, it’s well tolerated. So that early sequencing, I think we need some sort of guidelines and consensus and what we discussed today, or Amit very eloquently put forward, was a very straightforward pathway which was very understandable for the difference between waiting until symptomatic progression versus early radiological progression. I think that’s a very, very important aspect of the timing and perhaps you need to write an article about this yourself in a very accessible form to reiterate this situation.
NC: Fantastic. So, as you can see, we’ve had a wide-ranging discussion on the whole spectrum of prostate cancer. There’s more to follow. We’ve got some certainties; we have some grey areas and we have some areas where we really need to improve our knowledge and that’s the purpose of bringing together an international audience which has been done at the PROSCA 2018 meeting here in Frankfurt. I’d like to thank our experts for their expert and illuminating commentary. Thank you very much.
