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Earlier Detection of Prostate Cancer Bone Metastases

Panelists: Joe OSullivan, MD, Queens University; Nicholas James, MBBS, PhD University of Birmingham; Noel Clarke, MBBS, Christie Hospital
Published: Thursday, Jan 03, 2019



Transcript: 

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: We have these new imaging modalities available, including whole-body MRIs [magnetic resonance imaging exams], diffusion weighing, PSMA [prostate-specific membrane antigen] and diagnostics. We will likely see earlier diagnoses of bone metastases; is this clinically relevant?

Noel Clarke, MBBS, FRCS, ChM: Well, the lid has been taken off Pandora’s box, and it’s not going to be put back on anytime soon. In that sense, it is clinically relevant because people are using it. The problem is, as an international community we don’t know what this means. If one takes PSMA-PET [positron emission tomography] imaging in a country like Australia, where it’s cheap and everyone can get it, there’s an issue relating to interpretation, stage migration, and so on.

The other side of the coin is the whole-body MRI—it’s very resource consumptive; it takes a long time and extensive radiologist reporting, and it is expensive. It’s fair to say that we don’t know what some of those lesions are, either. There’s no real way of accessing it unless there’s a big metastasis, in which case you would expect to pick it up on some other imaging modality. That leaves us with the question of how we deal with it; I think that we’ll have to feel our way through it. In some circumstances, we’re able to test it out against standard imaging. We have a new arm planned for the STAMPEDE study, where we’re looking at basic scanning, which is bone scan and CT scan. There will be a parallel group who have had PSMA scans. This won’t determine whether they have the treatment or not. I think there will be a big stage migration, and I think more patients will get treated.

This calls into question the issue of dormancy; we’ve never really understood it. If we sampled bone marrow, for example, in prostate cancer and breast cancer patients, we can see cells that are in the bone marrow. We also know that if a patient has a radical prostatectomy for high-risk disease, up to a third of them will have microscopic metastatic lymph node disease, and a proportion of those will not progress at all. This is clinically relevant insofar as it’s going to influence practice. People need to think about whether they should use the standard methods for deciding on treatment triggers or whether they will move to PSMA-based options. We’ll fall in the cracks through the middle, actually.

Nicholas James, MD: We know for the nonmetastatic high-risk disease that radical radiotherapy to the prostate improves survival. If you did a PSMA-PET scan on the patients in that trial, they would be metastatic, for sure, which is why the control arm was given only hormone therapy, because it was viewed as a metastatic disease. You would then know the number of those who were metastatic. But they would probably still have benefited, as we now know from the STAMPEDE trial, a low-volume metastatic trial. If you said, “This patient is metastatic, so we’re not going to treat him” instead of “If we do the CT and bone scan, we are going to treat him,” we would have made the wrong decision. If you want to get the results that you saw in the trial, you have to do the same regimen from the trial. If you change the staging modalities, you’ve got to make sure you don’t reclassify patients erroneously into the wrong treatment decisions.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: It would be a real shame if patients started on more curative therapy.

Nicholas James, MD: Something else that will happen—which has been happening anyway with this trend, which we’ve observed in our centers—is that giving less treatment and more imaging is going to drive up the use of stereotactic radiotherapy because, although the tariffs are quite high, in reality the cost of it is only $3,000 to $4,000. If it’s a treatment that turns out to prolong survival, as it appears to be, it’s a very cheap way to prolong survival.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Exactly.

Nicholas James, MD: You’re sparing adverse effects of long-term systemic therapies. The trend that’s going to be driven by better imaging is an increased use of stereotactic radiotherapy. The question of whether it’s oligometastatic or not almost doesn’t matter; you’re treating the 3 biggest lumps.

Transcript Edited for Clarity

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Transcript: 

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: We have these new imaging modalities available, including whole-body MRIs [magnetic resonance imaging exams], diffusion weighing, PSMA [prostate-specific membrane antigen] and diagnostics. We will likely see earlier diagnoses of bone metastases; is this clinically relevant?

Noel Clarke, MBBS, FRCS, ChM: Well, the lid has been taken off Pandora’s box, and it’s not going to be put back on anytime soon. In that sense, it is clinically relevant because people are using it. The problem is, as an international community we don’t know what this means. If one takes PSMA-PET [positron emission tomography] imaging in a country like Australia, where it’s cheap and everyone can get it, there’s an issue relating to interpretation, stage migration, and so on.

The other side of the coin is the whole-body MRI—it’s very resource consumptive; it takes a long time and extensive radiologist reporting, and it is expensive. It’s fair to say that we don’t know what some of those lesions are, either. There’s no real way of accessing it unless there’s a big metastasis, in which case you would expect to pick it up on some other imaging modality. That leaves us with the question of how we deal with it; I think that we’ll have to feel our way through it. In some circumstances, we’re able to test it out against standard imaging. We have a new arm planned for the STAMPEDE study, where we’re looking at basic scanning, which is bone scan and CT scan. There will be a parallel group who have had PSMA scans. This won’t determine whether they have the treatment or not. I think there will be a big stage migration, and I think more patients will get treated.

This calls into question the issue of dormancy; we’ve never really understood it. If we sampled bone marrow, for example, in prostate cancer and breast cancer patients, we can see cells that are in the bone marrow. We also know that if a patient has a radical prostatectomy for high-risk disease, up to a third of them will have microscopic metastatic lymph node disease, and a proportion of those will not progress at all. This is clinically relevant insofar as it’s going to influence practice. People need to think about whether they should use the standard methods for deciding on treatment triggers or whether they will move to PSMA-based options. We’ll fall in the cracks through the middle, actually.

Nicholas James, MD: We know for the nonmetastatic high-risk disease that radical radiotherapy to the prostate improves survival. If you did a PSMA-PET scan on the patients in that trial, they would be metastatic, for sure, which is why the control arm was given only hormone therapy, because it was viewed as a metastatic disease. You would then know the number of those who were metastatic. But they would probably still have benefited, as we now know from the STAMPEDE trial, a low-volume metastatic trial. If you said, “This patient is metastatic, so we’re not going to treat him” instead of “If we do the CT and bone scan, we are going to treat him,” we would have made the wrong decision. If you want to get the results that you saw in the trial, you have to do the same regimen from the trial. If you change the staging modalities, you’ve got to make sure you don’t reclassify patients erroneously into the wrong treatment decisions.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: It would be a real shame if patients started on more curative therapy.

Nicholas James, MD: Something else that will happen—which has been happening anyway with this trend, which we’ve observed in our centers—is that giving less treatment and more imaging is going to drive up the use of stereotactic radiotherapy because, although the tariffs are quite high, in reality the cost of it is only $3,000 to $4,000. If it’s a treatment that turns out to prolong survival, as it appears to be, it’s a very cheap way to prolong survival.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Exactly.

Nicholas James, MD: You’re sparing adverse effects of long-term systemic therapies. The trend that’s going to be driven by better imaging is an increased use of stereotactic radiotherapy. The question of whether it’s oligometastatic or not almost doesn’t matter; you’re treating the 3 biggest lumps.

Transcript Edited for Clarity
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Community Practice Connections™: 2nd Annual International Congress on Oncology Pathology™Aug 31, 20191.5
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