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Unraveling Prostate Cancer Response: PSMA PET Sheds New Light on Treatment Effectiveness - Andrei Gafita & Wolfgang Fendler
January 30, 2023
In a recent led by Phillip Koo, Andrei Gafita and Wolfgang Fendler provide valuable insights on their innovative research, demonstrating the potential of PSMA PET imaging as a response to therapy tool in prostate cancer. Their study highlights the inconsistencies between PSMA PET responders and PSA levels, with about 50% of patients exhibiting this discrepancy. They found that PSMA PET imaging may offer greater prognostic accuracy for survival, even when PSA levels do not indicate treatment response or progression. As a result, PSMA PET's total tumor volume could serve as an independent biomarker, offering a new response tool. Looking ahead, both doctors anticipate further validation of these findings through prospective trials and broader application of the RECIP criteria in clinical trials, with the hope of harnessing PSMA PET's potential to enhance treatment response evaluation and prognosis accuracy.
Biographies:
Andrei Gafita, MD, Postdoctoral Scholar, Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA
Wolfgang Fendler, MD, Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK), University Hospital Essen, Essen, Germany
Phillip J. Koo, MD, Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center in Arizona
Biographies:
Andrei Gafita, MD, Postdoctoral Scholar, Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA
Wolfgang Fendler, MD, Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK), University Hospital Essen, Essen, Germany
Phillip J. Koo, MD, Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center in Arizona
Read the Full Video Transcript
Phillip Koo: Hello, my name is Phillip Koo and welcome back to UroToday. We are having a discussion today about response criteria in prostate cancer, and we have with us Dr. Andrei Gafita and Dr. Wolfgang Fendler, who spoke earlier about their landmark study about using PSMA as a response to therapy tool. An interesting topic within that larger discussion is how you handle patients who might be PSMA PET responders, but have a PSA discrepancy where it rises, or the vice versa, where the PSMA looks worse but the PSA levels improve. I know you guys have some data on this, maybe you could share with us some of the findings that you've seen with those discrepant PSMA PET imaging versus PSA responders.
Andrei Gafita: Sure. Would be our pleasure. We looked for treatment response in PSMA PET, which was assessed by RECIP criteria, and also PSA changes. And we've noticed that at 12 weeks, patients who actually did not have a PSA response, a PSA declined greater than 50%, but a response in PSMA PET by RECIP, they had significantly longer survival than those who did not have a response in PSMA pet. And vice versa, patients who did not have a PSA progression, so the treatment will not be discontinued, we've seen in these patients that about 50% of them had a progression by PSMA PET and they had a significantly shorter overall survival compared to those without a progression in PSMA PET. So these initial signals suggest that PSMA PET might have added value to PSA as a treatment response biomarker.
Phillip Koo: This is fascinating, because oftentimes, whether it's physician or even patients there's that hyper focus on PSA. And what oftentimes we don't think about is PSA might respond, but it actually might rise at a more rapid pace following treatment. But being able to visualize how the treatment is working with a PSMA PET clearly, in your study, shows signal that it might be a better biomarker, better response, so I think this is fascinating. Dr. Fendler, your thoughts?
Wolfgang Fendler: I agree, especially in the advanced prostate cancer, it can get very challenging to use PSA as a response biomarker, because in some of the studies it's been prognostic, and many studies it did not show an association with over survival. But the PSMA PET offers now an independent biomarker, an independent endpoint. The PSMA PET's Total tumor volume can now be used as a new response tool and can also be assessed in addition in combination, but also head-to-head to find out if this can offer, in the setting of advanced prostate cancer, maybe more prognostic accuracy for overall survival.
Phillip Koo: In your study. Do you know what percentage of patients had that discrepancy between PSMA PET and PSA?
Andrei Gafita: About 50% of them.
Phillip Koo: Wow. And did you notice anything, did the discrepancy occur in patients who had more lines of therapy up front, later in their disease where the disease might be a little more heterogeneous, or no sign?
Andrei Gafita: We haven't looked into that, but I think that's a great research question for next study.
Phillip Koo: Great. All right. So, speaking of next studies, Dr. Fendler, what are your thoughts on how we take this to the next level?
Wolfgang Fendler: I think the RECIP was now used and validated in the cohort of patients who underwent lutetium PSMA therapy, and this is kind of opening the door for using PSMA PET as a response biomarker. But we need, certainly, more data on the prognostic value of RECIP criteria. So I think what this can do is to encourage study groups to include RECIP criteria as much as possible into clinical trials in the setting of metastatic prostate cancer to evaluate this. It could be an add-on imaging to evaluate the value of RECIP in clinical trials and gather more data, maybe also in other treatments than lutetium PSMA, to correlate and assess the prognostic value for RECIP on overall survival in as many studies as possible so we can get more confidence and also more clinical scenarios where this could be used.
Phillip Koo: Wonderful, very exciting, Dr. Gafita, any last thoughts?
Andrei Gafita: We are looking forward to start some clinical trials with RECIP to validate in a prospective setting, and also to see RECIP being used in clinical practice.
Phillip Koo: This is so wonderful, and it's also wonderful to see more of our nuclear medicine physicians take charge and lead a lot of these novel clinical trials. So congratulations, and thank you on behalf of the whole nuclear medicine and prostate cancer community for this wonderful work.
Wolfgang Fendler: Thank you.
Andrei Gafita: Thank you so much.
Phillip Koo: Hello, my name is Phillip Koo and welcome back to UroToday. We are having a discussion today about response criteria in prostate cancer, and we have with us Dr. Andrei Gafita and Dr. Wolfgang Fendler, who spoke earlier about their landmark study about using PSMA as a response to therapy tool. An interesting topic within that larger discussion is how you handle patients who might be PSMA PET responders, but have a PSA discrepancy where it rises, or the vice versa, where the PSMA looks worse but the PSA levels improve. I know you guys have some data on this, maybe you could share with us some of the findings that you've seen with those discrepant PSMA PET imaging versus PSA responders.
Andrei Gafita: Sure. Would be our pleasure. We looked for treatment response in PSMA PET, which was assessed by RECIP criteria, and also PSA changes. And we've noticed that at 12 weeks, patients who actually did not have a PSA response, a PSA declined greater than 50%, but a response in PSMA PET by RECIP, they had significantly longer survival than those who did not have a response in PSMA pet. And vice versa, patients who did not have a PSA progression, so the treatment will not be discontinued, we've seen in these patients that about 50% of them had a progression by PSMA PET and they had a significantly shorter overall survival compared to those without a progression in PSMA PET. So these initial signals suggest that PSMA PET might have added value to PSA as a treatment response biomarker.
Phillip Koo: This is fascinating, because oftentimes, whether it's physician or even patients there's that hyper focus on PSA. And what oftentimes we don't think about is PSA might respond, but it actually might rise at a more rapid pace following treatment. But being able to visualize how the treatment is working with a PSMA PET clearly, in your study, shows signal that it might be a better biomarker, better response, so I think this is fascinating. Dr. Fendler, your thoughts?
Wolfgang Fendler: I agree, especially in the advanced prostate cancer, it can get very challenging to use PSA as a response biomarker, because in some of the studies it's been prognostic, and many studies it did not show an association with over survival. But the PSMA PET offers now an independent biomarker, an independent endpoint. The PSMA PET's Total tumor volume can now be used as a new response tool and can also be assessed in addition in combination, but also head-to-head to find out if this can offer, in the setting of advanced prostate cancer, maybe more prognostic accuracy for overall survival.
Phillip Koo: In your study. Do you know what percentage of patients had that discrepancy between PSMA PET and PSA?
Andrei Gafita: About 50% of them.
Phillip Koo: Wow. And did you notice anything, did the discrepancy occur in patients who had more lines of therapy up front, later in their disease where the disease might be a little more heterogeneous, or no sign?
Andrei Gafita: We haven't looked into that, but I think that's a great research question for next study.
Phillip Koo: Great. All right. So, speaking of next studies, Dr. Fendler, what are your thoughts on how we take this to the next level?
Wolfgang Fendler: I think the RECIP was now used and validated in the cohort of patients who underwent lutetium PSMA therapy, and this is kind of opening the door for using PSMA PET as a response biomarker. But we need, certainly, more data on the prognostic value of RECIP criteria. So I think what this can do is to encourage study groups to include RECIP criteria as much as possible into clinical trials in the setting of metastatic prostate cancer to evaluate this. It could be an add-on imaging to evaluate the value of RECIP in clinical trials and gather more data, maybe also in other treatments than lutetium PSMA, to correlate and assess the prognostic value for RECIP on overall survival in as many studies as possible so we can get more confidence and also more clinical scenarios where this could be used.
Phillip Koo: Wonderful, very exciting, Dr. Gafita, any last thoughts?
Andrei Gafita: We are looking forward to start some clinical trials with RECIP to validate in a prospective setting, and also to see RECIP being used in clinical practice.
Phillip Koo: This is so wonderful, and it's also wonderful to see more of our nuclear medicine physicians take charge and lead a lot of these novel clinical trials. So congratulations, and thank you on behalf of the whole nuclear medicine and prostate cancer community for this wonderful work.
Wolfgang Fendler: Thank you.
Andrei Gafita: Thank you so much.