Panelists: Joe OSullivan, MD, FRCPI, FFRRCSI, FRCR, The Northern Ireland Cancer Centre, Belfast City Hospital; Johann de Bono, PhD, MB, ChB, Institute of Cancer Research, Royal Marsden Hospital; Chris Parker, MD, FRCR, MRCP, Institute of Cancer Research, Royal Marsden Hospital; Bertrand Tombal, MD, PhD, Cliniques Universitaires Saint-Luc
Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Bertrand, I’m going to start with you. How do you think next-generation imaging will be used for earlier detection of metastatic disease?
Bertrand Tombal, MD, PhD: As you know, in Europe, they are already used. The first observation is that you see more and you see it before. That’s a no-brainer. If you switch from a bone scan or CT scan to PET PSMA, PET choline, or whole-body MRI, you’re going to see more and you’re going to see it earlier. But you have to keep in mind that none of these techniques have a diagnostic accuracy of 100% and what you gain in sensitivity, you may sometimes lose in specificity. So, you’re going to see more, but some of this will not be cancer. Actually, I’m going to take the example of PET PSMA. If it drives treatment change, you have to realize it’s not perfect. In urology, for instance, these technologies, they’re used at the time of PSA recurrence after radical treatment. And so, we see all these papers now popping up where instead of doing a CT scan or bone scan, people do a PET PSMA scan. They see what they call oligometastatic deposit, which is actually metastatic deposit that the surgeon feels he can remove or the radiation oncologist feels he can irradiate.
But then, if you look at the literature, you will see that, overall, 20% is not cancer and that patients actually still progress while everything is being treated or removed. So, they are new tools, but, once again, we have not shown that it improves the care pathway in the overall survival of the patient. I don’t say we should not use it, but we have to keep that in mind. That’s important.
But then, with this technology opening, to me what is much more important is that we have started doing something we haven’t done before. In high-risk patients, very advanced patients, we monitor the response to treatment. That’s where we’re seeing a different world. I know Johann has made the same observation where, especially when you look at bone metastatic disease, you realize that the disease is absolutely heterogeneous, that you can see multiple response in multiple metastases and that you can know and envision a new generation of trials when you use that imaging.
Is new imaging better in terms of seeing more than the other one? Yes. Are they affordable? That depends on how much money the people who do the imaging want to make off of the imaging. A PET PSMA scan in my country is about €400. A whole-body MRI is €500, which can be €5000 in some other countries. So, if you have access to this technique, you’re going to see a different disease. They may change diagnoses, for sure. They may change initial therapy, but to me, one of the most important advantages in very advanced disease is being able now to allow better monitoring of the response. And that’s something for which we have improved our capability.
Chris Parker, MD, FRCR, MRCP: I strongly agree with what you’re saying about assessing response in bone metastases, and, in my practice, that’s particularly helpful when it comes to treatment with radium-223. Because, actually, it’s quite hard to assess response in any other way. PSA is not a good marker of response to radium. Brain scans and CT scans don’t help to evaluate response in bone metastases, but we’re using whole-body diffusion-weighted MRI and for the first time, we can certainly see who’s benefitting and who’s not.
Johann de Bono, PhD, MB, ChB: The other major impact here, and I think Bertrand alluded to this, is stage migration. I think we’ll see a lot less M0 disease and these patients with a rising PSA will be deemed M1. Therefore, this whole concept of treating M0 patients and looking, at that time, at metastasis may actually have very limited impact on the field.
Bertrand Tombal, MD, PhD: One of the messages I give many times when I speak about these techniques is that PSA is no longer a trigger to treat, but a trigger to image. And then you realize how difficult it is to tell somebody with a rising PSA that you’re going to delay treatment. It’s not easy to say, “You’ve got a rising PSA, but your PET PSMA is negative, so we’re not going to trigger treatment.” People often say with PET PSMA, “You’re treating a lot of patients based on this.” But they don’t see the other part, which is the number of patients we save from aggressive treatment because they have a negative PET PSMA or a negative whole-body MRI. And then, you have a small portion in-between, where you have what I call suspicious imaging. We may be overtreating them, but we also save a lot of useless treatment in these patients.
Johann de Bono, PhD, MB, ChB: What’s particularly interesting for me, from practical experience, is that some patients drive their own therapy. One of my colleagues, actually, who had a rising PSA and a normal scan wanted prostatectomy. He had radical radiotherapy. It was interesting, because the prostatectomy confirmed that he had some tumor in the prostate. But despite outstanding surgery, he still had a high PSA post surgery, which makes your point that even if you can see it on the scan, that doesn’t mean treating that primary further is beneficial. We need more data on this subject.