Performance of rhPSMA 7.3 (18F) PET Ligand in Suspected Prostate Cancer Recurrence - UroToday Journal Club - Christopher Wallis & Zachary Klaassen

April 22, 2022

Christopher Wallis and Zachary Klaassen discuss the article published in the Journal of Nuclear Medicine reporting on the first retrospective data on the detection efficacy and potential impact of 18F-rhPSMA-7.3 on clinical management in a homogeneous cohort of patients with biochemical recurrence after radical prostatectomy, and prior to any salvage therapy. 18F-rhPSMA-7.3 is under investigation in two multicenter phase III trials for PET imaging. In this publication, the first retrospective data on the detection efficacy of 18F-rhPSMA-7.3 and its potential impact on clinical management in a homogeneous cohort of patients with biochemical recurrence after radical prostatectomy, and prior to any salvage therapy are reported. 

Biographies:

Christopher J.D. Wallis, MD, Ph.D., Assistant Professor in the Division of Urology at the University of Toronto.

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Georgia Cancer Center


Read the Full Video Transcript

Christopher Wallis: Hello, and thank you for joining us for this UroToday Journal Club discussion. Today, we're discussing a recent publication entitled, the Detection Efficacy of 18F-rhPSMA-7.3 PET/CT and Impact on Management in Patients with Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy and Before Potential Salvage Treatment.

I'm Chris Wallis. I'm an Assistant Professor in the Division of Urology at the University of Toronto. With me today, is Zach Klaassen, Assistant Professor in the Division of Urology at the Medical College of Georgia.

You can see here, the citation for this publication recently published in JNM.

Biochemical recurrence is a relatively common outcome following initial curative-intent to treatment for localized prostate cancer, whether by surgery or radiotherapy. At low levels of PSA, conventional imaging performs quite poorly in localizing recurrent disease.

There are, however, alternative approaches, such as the PET imaging, which have been explored. And a 68Ga-PSMA-11 PET has been extensively studied, and along with DCFPyL, is now guideline recommended for the investigation of patients with biochemical recurrence, following their initial local therapy.

You can see here, the PSMA target being a transmembrane protein, with a variety of different ligans, used at this substrate recognition site, that's extracellular.

PSMA-PET leads to frequent changes in management, as you can see here. One example using 18F-DCFPyL, where we have approximately, 70 age percent of the population that has a change in management. However, when we try and compare across trials, with considerable heterogeneity, based in part on different PSA levels, PET positivity, and the definition of what a change in management is.

Additionally, as we alluded to before, 68 gallium was among the first ligands used in PSMA imaging, but it has notable limitations, including a short half life, labor intensive production, which prevents the distribution and urinary excretion, and which makes some interpretation more difficult. In contrast, fluoridated approaches, including 18F-PSMA-1007, 18F-DCFPyL, and 18F-rhPSMA-7, have notable benefits, including a longer half life, lower positron energy, allowing for better resolution, and lower genitourinary accumulation. These however, target the same recognition site.

So rhPSMA is the contraction of radio hybrid PSMA ligands. And this represents a novel class of radiopharmaceuticals. They may be labeled with 18 fluoride, or with other radiometals, including 68 gallium, 177 lutetium, or 225 actinium. Thus, whether used with 18 fluoride or 60 gallium, for diagnostic imaging purposes, or lutetium, for theranostic purposes, and the same ligand may be used with different radiometals.

18F-rhPSMA-7 has four stereoisomers. And on the basis of improved pharmacokinetics, tumor accumulation, and low renal uptake, RHPSMA-7.3 was the preferred isomer selected, and therefore, used in the study.

The goal of this study, was to assess the detection accuracy of 18F-rhPSMA-7.3. And the impact of the use of the scan on patient management among a select group of patients with biochemical recurrence following their radical prostatectomy.

Authors included 242 patients in a retrospective cohort study, and it accrued these patients on the basis of biochemical recurrence following initial radical prostatectomy, who received imaging with 18F-rhPSMA-7.3, between September of 2018, and October 2019.

Patients could not have had prior salvage therapy with either radiotherapy, salvage surgery, or prior androgen deprivation.

In terms of imaging, patients received a mean of 332 MBq, approximately 73 minutes before scan. PET/CT was performed using a Biograph mCT flow scanner. And initially, a diagnostic CT was performed in the portal venous phase, followed by a PET scan. All patients received diluted oral contrast, as well as Lasix. And standard correction was performed, in terms of emission data, as well as reconstruction, and post reconstruction smoothing.

The images were interpreted by board certified nuclear meta medicine physicians.

And all lesions suggestive of recurrence were noted.

Any focal up trace that was above the levels of the blood-pool without physiologic uptake was considered to be suggestive of disease recurrence.

The PROMISE criteria were used for lesion assessment, and then, lesions were categorized using the miTNM framework.

The authors then, assessed the impact of these scan results on patient management. To do so, they first created a simulated interdisciplinary tumor board, including a urological oncologist, radiation oncologist, and nuclear medicine physician.

Using national and international guidelines, they made treatment decisions based on clinical data.

Subsequently, PSA imaging results were presented. And then, a post-imaging treatment recommendation was made.

The authors compared changes from pre-imaging to post-imaging, on the basis of treatment that was grouped into five categories; including radiation therapy, surgery, systemic therapy, multimodal therapy, or no recommended therapy. A change within a treatment modality was deemed minor. Whereas, a change between modalities was deemed a major change.

In terms of statistical analysis, the authors assessed the detection rate of presumed recurrent sites, according to baseline PSA. And they assessed this, both at the patient level, and at the region level. Mann-Whitney U test was used to compare PSA levels between patients with PSMA evidence of disease and without. And the proportion of patients with management changes was determined, and a Sankey diagram was used to visualize this.

Now I'm going to hand it over to Zach, to walk us through the results of this study.

Zachary Klaassen: Thanks very much, Chris, for that great introduction.

So this is the patient characteristics of baseline table. And you can see here, that the age at PET/CT scan was 72. The most common ISA grade group was grade group two, at 28.5%. In terms of pathological primary staging, most commonly was T3 at 45.9%. Secondly, T2 at 39.3%. The majority of these patients were pathological N0, at 62.4%. With regards to positive margin status. 18.2% of patients had a positive margin. Initial PSA median was 10.5. And the time between surgery and PET scan was 50 months. Last PSA value before PET/CT scan was a median of 0.60.

This figure looks at the overall detection rate of rhPSMA-7.3 stratified by PSA. And we can see here, an impressive detection rate between 0.2 and 0.5 PSA of 61.8%, which increases with increasing PSA. So at 0.5 to one, 67.9% of PSA of one to two, 81.1%, and a PSA of greater than two, 5.7%.

This figure looks at the localization of the lesions, using the miTNM classification, as well as stratified by PSA. So in the bottom here, we'll go through the legend real quick. miTr is essentially, prostate bed, and this is in blue. miN1ab is in orange. miM1a is in gray. miM1b is in yellow. And miM1c is in dark blue.

So looking at the lowest PSA of 0.2 to 0.5, even with a low PSA, we see, not surprised, 30.2% in the prostate, but we do see lymph node involvement, 20.6%, and M1b, even with this low PSA, at 8.8%. As we increase the PSA, more prostate bed detection, ranging from 44.6%, up to 64.9 and 61.7%. Similarly, we see more lymph node involvement, 25% at a PSA of 0.5 to one, up to 53% with a PSA greater than two. And again, M1b, 7.1%, PSA 0.5 to one, 10.8 PSA of one to two, and upwards of 29% with a PSA of greater than two.

This table looks at the post-PET management category details. And so on the left here, is the potential management before PSMA-PET. In the middle is potential management after PSMA-PET. And we see here, in terms of a potential management before PET of local radiotherapy to the prostate bed, this essentially was unchanged in 19% of patients. However, after the PSMA-PET, this was changed to local radiotherapy plus an integrated boost in 16% of patients. And in 5% of the patients, local therapy, plus a boost, plus ADT.

Moving down to local radiotherapy plus ADT before PSMA-PET, no change in 7% of patients. However, with an addition of an integrated boost in 24% of patients. And actually, 4% of patients undergoing salvage lymphadenectomy after the PSMA-PET scan was performed.

This is the Sankey diagram, which Chris mentioned in the methods, for the pre to post PET change and potential management. And importantly, therapeutic management changed after PET/CT in 60.2% of patients. This was categorized as a major change in 22.3% of patients, and a minor change in 40.9% of patients.

Two items to look at and highlight here. As I mentioned in the previous table, local radiotherapy, and then the green line here, leading to local radiotherapy plus integrated boost, was quite common, as well as local radiotherapy plus ADT pre-imaging, to local radiotherapy, plus a boost, plus ADT, after PET imaging.

This figure looks at the potential management change after PSMA-PET stratified by PSA values. I've kind of summarized the findings here on the right. In terms of management change by PSA, for a PSA of 0.2 to 0.5. 60.7% had a change in management for PSA of 0.5 to less than one, 67.9% had a change in management. And for a PSA of one to two, 86.5% of patients had a change in management after the PSMA-PET scan.

This table looks at potential management change according to lesion localization. In terms of local recurrence, there was 118 patients. The majority that had a change, were minor changes in 80 of these 118 patients. However, when we look at pelvic lymph node involvement, there was 70% of patients. 47 of these 70 patients had a major change in management after PET imaging. Again, looking at the bottom here, bone metastases, 32 patients, of which 23 had a major change in management after PSMA-PET imaging.

Sort of the final figure in the results here. This is several examples provided by the authors, looking at actual images and changes in management, after patients underwent rhPSMA-7.3. So on the left, the first patient is a 70 year old male, with a PSA of 0.49, which did not show anything on PET/CT scan, but it did show an uptake in the right prostate bed on PSMA-PET imaging. And you can see this here, highlighted with the red arrow. And this management change was from radiotherapy to radiotherapy with an integrated boost. And this was categorized as a minor change in management.

The second case is a 57 year old male, with a PSA of 1.0, who had uptake in the left pelvic lymph node, as you can see here, on both the CT scan and the PET imaging. And this management change was from radiotherapy plus short term ADT, before PET imaging, to a salvage lymph node dissection after imaging. And this was categorized asa major change.

The final case is on the right. You can see a 62 year old male, with a PSA of 0.3, with uptake in the left iliac bone on PET imaging, as signified by the arrow here. And this management change was from ADT before PSMA-PET to SBRT after imaging, which was also categorized as a major change in management.

So several discussions points from this study. In this retrospective analysis of a large cohort of men with biochemical recurrence after radical prostatectomy and before savage therapy, rhPSMA-7.3 PET/CT detected and localized prostate cancer in 72.3% of patients. This is consistent with other PET tracers, the detection rate of rhPSMA-7.3 increases with PSA level, as we showed in the previous slides.

rhPSMA-7.3 PET/CT improved detection at low PSAs, less than 0.5. And you can see here, that in this study, it was 39% for rhPSMA-7.3, versus only 20% for Ga PSMA-11.

As we've shown in this study, and then in other studies, improved staging leads to changes in management, which occurred in 63.2% of patients undergoing rhPSMA-7.3, and previously reported as 68% for Ga PSMA-11.

So in conclusion, in this large population of patients with recurrent prostate cancer after radical prostatectomy and before savage therapy, rhPSMA-7.3 PET/CT offered high detection rates, at least consistent with those for Ga PSMA-11.

Incorporation of rhPSMA-7.3 PET/CT results into simulated clinical decision making led to a change in management in nearly two thirds of patients, potentially paving the way to personalized medicine.

Thank you very much for your attention. We hope you enjoyed this UroToday Journal Club discussion.

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