How to Manage Patients with Low-Volume on Conventional and High-Volume on NGI "Presentation" - Dana Rathkopf
November 15, 2024
At the 2024 Advanced Prostate Cancer Consensus Conference (APCCC), Dana Rathkopf addresses the complex challenge of managing prostate cancer patients who show low-volume disease on conventional imaging but high-volume disease on next-generation PET imaging. The presentation explores evidence suggesting PET-only metastases may be more indolent than conventional imaging-visible disease.
Biographies:
Dana Rathkopf, MD, Genitourinary Oncologist, Memorial Sloan Kettering Cancer Center, New York, NY
Biographies:
Dana Rathkopf, MD, Genitourinary Oncologist, Memorial Sloan Kettering Cancer Center, New York, NY
Read the Full Video Transcript
Dana Rathkopf: So it's going to take me all 10 minutes just to read my topic. How to manage patients with low-volume disease on conventional imaging and high-volume on next-generation imaging. These are my disclosures. So we've heard quite a bit over the past two days about clinical risk groups and treatment selection, and you can tell already it's already complex as is. And now, we need to incorporate next-generation imaging into the current treatment paradigm.
So the clinical conundrum of PET imaging for initial staging and treatment of metastatic hormone-sensitive prostate cancer includes a lot of pros. There's increased accuracy relative to conventional imaging. It's better at detecting small lymph nodes and early lytic bone disease, even at low PSA. There's potential for targeted treatment options based on imaging results.
But there are also, I'm not going to say contraindications, but considerations that we need to think about. Indeterminate findings can delay treatment and cause patient distress. And this is really important to think about in this population because a lot of patients are going to be diagnosed for the first time with metastatic hormone-sensitive prostate cancer, and they're trying to understand their prognosis, their extensive disease, what's coming, what their treatment options are.
And when you have discordant imaging findings and additional tests that need to happen, and this delays the treatment plan, it can be really stressful for patients and stressful for us as clinicians trying to adjudicate these findings.
We don't really know what the importance of PET-only metastasis is. If you have conventional imaging occult lesions but lesions on PET imaging, what do those lesions mean? Are they indolent, perhaps? Or maybe they're a harbinger of something more aggressive to come, and you need to escalate therapy. And really, at the crux of all of this is do PET-directed treatment decisions lead to better clinical outcomes?
This was an interesting multicenter, international study that was retrospective, but it looked at clinical and genomic differences between metachronous oligometastatic hormone-sensitive prostate cancer. They broke the patients up into conventional imaging, where you could see metastasis, and PET-only imaging, where you saw metastasis.
What they saw was that in the PET-only metastasis group, there were fewer high-risk mutations and better survival. And this is food for thought today in the context of this talk because it makes you wonder, can we extrapolate this concept of PET-only disease potentially being more indolent to the polymetastatic setting?
It's important to point out, and we already know this, that the prognostic clinical subgroups are very helpful, but they're not one-size-fits-all. And this is true more so than ever now that we have next-generation imaging. This study on the right was looking at patients that had had conventional imaging and PET imaging. And what you can see is that 40% of patients that had low volume on conventional imaging actually shifted their subgroup on PET.
And I'm going to point out that they not only shifted their subgroup up to more aggressive disease, but also down to more localized disease. And so we need to be very, very cautious when trying to retrofit PET findings into conventional imaging-defined volume subgroups. A high-volume PET imaging patient might not be a high-volume conventional imaging patient in terms of prognosis.
I think the Stampede II trial illustrates this nicely. I appreciate that they're using different terminology for the PET imaging, oligometastatic and polymetastatic. And I think this helps in terms of confusion, in terms of prognoses. Calling a high-volume PET patient is not the same as conventional imaging. So I very much favor this oligometastatic/polymetastatic terminology.
And this is just one example of multiple studies that we've seen over the past several days that are trying to incorporate next-generation imaging into the study designs so we can better understand the natural history and how it impacts outcomes.
But in the meantime, many of us are going back to clinic next week, and we are going to be seeing patients that have discordant imaging, conventional imaging low volume, and PET imaging high volume. And even in our own APCC conference in 2022, we were split pretty much down the middle as how to manage this.
There have been other consensus groups also giving guidance, such as treatment should not be changed based on next-generation imaging findings, or patients should not be denied radical local treatment solely because of metastatic lesions on MGI. And in principle, I agree with this. But in practice, it's much more difficult.
So here's an extreme example. This is a patient with low-volume disease on conventional imaging, 58, newly diagnosed, fit, Gleason 9 prostate cancer. Reasonable minds might differ on the treatment path here, and that's fine, as it should be. It's not one-size-fits-all, as I mentioned. But more or less, if you were going to treat this patient, I think certainly androgen deprivation therapy and an androgen receptor pathway inhibitor.
Personally, I probably wouldn't use docetaxel unless I had some more compelling evidence. Because there is limited data for this low-volume—or immature data for this low-volume group of patients. I would certainly think about prostate radiation therapy and plus or minus metastasis-directed therapy. I think we all do it in our clinics, and that's fine. But we don't really have a lot of good prospective data for this yet.
But this is what this patient's PET scan looks like. Imagine how the patient feels. And for us, it's very confusing. We can't ignore this finding and we shouldn't ignore this finding. But how does it affect our treatment plan? Well, for me, I would still use androgen deprivation therapy and an androgen receptor pathway inhibitor. I think there's good data for that in all stages of disease.
It might make me think a little bit more about docetaxel. I mentioned that there's limited and immature data, but not no data for low-volume de novo disease. It would certainly make me think a little bit more about whether or not to use prostate radiation. But we've heard quite a number of talks yesterday talking about radiation to the prostate for local control is an option. And it probably would lead me against doing metastasis-directed therapy. We know the STOMP and ORIOLE trials that did incorporate PET imaging showed that if you leave lesions behind, that doesn't really help the patients.
In conclusion, general principles for treating metastatic hormone-sensitive prostate cancer in the burgeoning age of PET imaging: I think that clinical subgroups should guide, but not decide treatment decisions. I mentioned that treating metastatic hormone-sensitive prostate cancer is complex in the beginning. And it's complex not just because of our treatment selections, but also because of the patients. Patients are complex and bring their own history and their own preferences to clinic, and we need to honor that in our treatment decisions.
I think we really need to be careful about terminology for PET findings, especially when they're discordant. I favor oligometastatic and polymetastatic as opposed to high-volume PET, low-volume PET. I feel that's confusing. And finally, PET imaging is just one piece of the treatment puzzle. Use caution because what you see is not always what you get.
And so for us, the metastatic hormone-sensitive prostate cancer treatment puzzle, if you will, there are many pieces. Our challenge is to put them together so that we can see the big picture and treat our patients best we can. Thank you.
Dana Rathkopf: So it's going to take me all 10 minutes just to read my topic. How to manage patients with low-volume disease on conventional imaging and high-volume on next-generation imaging. These are my disclosures. So we've heard quite a bit over the past two days about clinical risk groups and treatment selection, and you can tell already it's already complex as is. And now, we need to incorporate next-generation imaging into the current treatment paradigm.
So the clinical conundrum of PET imaging for initial staging and treatment of metastatic hormone-sensitive prostate cancer includes a lot of pros. There's increased accuracy relative to conventional imaging. It's better at detecting small lymph nodes and early lytic bone disease, even at low PSA. There's potential for targeted treatment options based on imaging results.
But there are also, I'm not going to say contraindications, but considerations that we need to think about. Indeterminate findings can delay treatment and cause patient distress. And this is really important to think about in this population because a lot of patients are going to be diagnosed for the first time with metastatic hormone-sensitive prostate cancer, and they're trying to understand their prognosis, their extensive disease, what's coming, what their treatment options are.
And when you have discordant imaging findings and additional tests that need to happen, and this delays the treatment plan, it can be really stressful for patients and stressful for us as clinicians trying to adjudicate these findings.
We don't really know what the importance of PET-only metastasis is. If you have conventional imaging occult lesions but lesions on PET imaging, what do those lesions mean? Are they indolent, perhaps? Or maybe they're a harbinger of something more aggressive to come, and you need to escalate therapy. And really, at the crux of all of this is do PET-directed treatment decisions lead to better clinical outcomes?
This was an interesting multicenter, international study that was retrospective, but it looked at clinical and genomic differences between metachronous oligometastatic hormone-sensitive prostate cancer. They broke the patients up into conventional imaging, where you could see metastasis, and PET-only imaging, where you saw metastasis.
What they saw was that in the PET-only metastasis group, there were fewer high-risk mutations and better survival. And this is food for thought today in the context of this talk because it makes you wonder, can we extrapolate this concept of PET-only disease potentially being more indolent to the polymetastatic setting?
It's important to point out, and we already know this, that the prognostic clinical subgroups are very helpful, but they're not one-size-fits-all. And this is true more so than ever now that we have next-generation imaging. This study on the right was looking at patients that had had conventional imaging and PET imaging. And what you can see is that 40% of patients that had low volume on conventional imaging actually shifted their subgroup on PET.
And I'm going to point out that they not only shifted their subgroup up to more aggressive disease, but also down to more localized disease. And so we need to be very, very cautious when trying to retrofit PET findings into conventional imaging-defined volume subgroups. A high-volume PET imaging patient might not be a high-volume conventional imaging patient in terms of prognosis.
I think the Stampede II trial illustrates this nicely. I appreciate that they're using different terminology for the PET imaging, oligometastatic and polymetastatic. And I think this helps in terms of confusion, in terms of prognoses. Calling a high-volume PET patient is not the same as conventional imaging. So I very much favor this oligometastatic/polymetastatic terminology.
And this is just one example of multiple studies that we've seen over the past several days that are trying to incorporate next-generation imaging into the study designs so we can better understand the natural history and how it impacts outcomes.
But in the meantime, many of us are going back to clinic next week, and we are going to be seeing patients that have discordant imaging, conventional imaging low volume, and PET imaging high volume. And even in our own APCC conference in 2022, we were split pretty much down the middle as how to manage this.
There have been other consensus groups also giving guidance, such as treatment should not be changed based on next-generation imaging findings, or patients should not be denied radical local treatment solely because of metastatic lesions on MGI. And in principle, I agree with this. But in practice, it's much more difficult.
So here's an extreme example. This is a patient with low-volume disease on conventional imaging, 58, newly diagnosed, fit, Gleason 9 prostate cancer. Reasonable minds might differ on the treatment path here, and that's fine, as it should be. It's not one-size-fits-all, as I mentioned. But more or less, if you were going to treat this patient, I think certainly androgen deprivation therapy and an androgen receptor pathway inhibitor.
Personally, I probably wouldn't use docetaxel unless I had some more compelling evidence. Because there is limited data for this low-volume—or immature data for this low-volume group of patients. I would certainly think about prostate radiation therapy and plus or minus metastasis-directed therapy. I think we all do it in our clinics, and that's fine. But we don't really have a lot of good prospective data for this yet.
But this is what this patient's PET scan looks like. Imagine how the patient feels. And for us, it's very confusing. We can't ignore this finding and we shouldn't ignore this finding. But how does it affect our treatment plan? Well, for me, I would still use androgen deprivation therapy and an androgen receptor pathway inhibitor. I think there's good data for that in all stages of disease.
It might make me think a little bit more about docetaxel. I mentioned that there's limited and immature data, but not no data for low-volume de novo disease. It would certainly make me think a little bit more about whether or not to use prostate radiation. But we've heard quite a number of talks yesterday talking about radiation to the prostate for local control is an option. And it probably would lead me against doing metastasis-directed therapy. We know the STOMP and ORIOLE trials that did incorporate PET imaging showed that if you leave lesions behind, that doesn't really help the patients.
In conclusion, general principles for treating metastatic hormone-sensitive prostate cancer in the burgeoning age of PET imaging: I think that clinical subgroups should guide, but not decide treatment decisions. I mentioned that treating metastatic hormone-sensitive prostate cancer is complex in the beginning. And it's complex not just because of our treatment selections, but also because of the patients. Patients are complex and bring their own history and their own preferences to clinic, and we need to honor that in our treatment decisions.
I think we really need to be careful about terminology for PET findings, especially when they're discordant. I favor oligometastatic and polymetastatic as opposed to high-volume PET, low-volume PET. I feel that's confusing. And finally, PET imaging is just one piece of the treatment puzzle. Use caution because what you see is not always what you get.
And so for us, the metastatic hormone-sensitive prostate cancer treatment puzzle, if you will, there are many pieces. Our challenge is to put them together so that we can see the big picture and treat our patients best we can. Thank you.