F-18-Labeled DCFPyL in Patients With Metastatic Prostate Cancer Undergoing Treatment With ADT – Esther Mena Gonzalez

July 21, 2021

In this presentation from Esther Mena Gonzalez, she discusses her team’s findings on the role of castration status or hormone-sensitive castrate-resistance data and androgen deprivation therapy (ADT) in the use of 18F DCFPyL PET/CT. She discussed the objective of her study to be to investigate the performance of 18F DCFPyL in her cohort of patients with documented metastatic prostate cancer who were undergoing treatment with ADT. The population for this study consisted of 37 patients with biopsy-proven prostate cancer with the presence of metastatic disease. 14 of those patients were metastatic castrate-sensitive patients, while 23 of them were metastatic castrate-resistant. The findings from Dr. Gonzalez’s study showed more detectable lesions in castrate-resistant, compared to castrate-sensitive, patients. Dr. Gonzalez concluded that the utility of PSMA targeted imaging in metastatic prostate cancer patients is dependent on patient’s castrate status and how long they have been on ADT. Looking ahead to a future study, Dr. Gonzalez plans on doing a longitudinal study with intermittent scans to assess for ADT utility over time.

Biographies:

Esther Mena Gonzalez, MD, Staff Clinician at the Molecular Imaging Branch (MIB). She is Board-Certified in the field of Nuclear Medicine. National Cancer Institute. NIH, Bethesda, MD

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.


Read the Full Video Transcript

Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University. I'm so excited to have here with me today, Dr. Esther Mena, who is a Nuclear Medicine Physician and a staff physician at the Molecular Imaging Branch of the National Cancer Institute. She's here to talk with me a little bit today about her presentation at the recent SNMMI meeting, where she talked about the role of the castration status or hormone-sensitive castrate resistance data and androgen deprivation therapy in the use of F18 DCFPyL PET/CT. Thank you so much for being here with me today, Dr. Mena.

Esther Mena Gonzalez: Thank you Dr. Morgans for the introduction on this kind invitation. I'm delighted for the opportunity to present about work on DCFPyL PET/CT from the Molecular Imaging Branch at the National Cancer Institute at NIH. This is a poster presentation of our work on DCFPyL PET in patients with metastatic prostate cancer that was recently presented at the Society of Nuclear Medicine and Molecular Imaging annual meeting. F-18-labeled DCFPyL targets prostate-specific membrane antigen, PSMA. A membrane-like a protein highly expressed in prostate cancer, and specifically in more aggressive tumors and metastatic disease. PSMA target imaging probes have been developed and demonstrate improved sensibility, sensitivity, and specificity for two more detections in patients with biochemical recurrence prostate cancer and metastatic prostate cancer. The performance of F-18-labeled DCFPyL may depend on patients castrate status and time from a hormone therapy exposure.

The objective of our study was to investigate the performance of F-18-labeled DCFPyL in our prospective cohort of patients with documented metastatic prostate cancer who were undergoing treatment with androgen deprivation therapy. This is our prospective institutional board review approved single institutional study that is actually actively recruiting patients. The population that we selected for this abstract was 37 patients with biopsy-proven prostate cancer, along with the presence of metastatic disease on conventional imaging. The median PSA was 6.3 with a wide range of PSA values. Out of 37 patients, 14 patients were metastatic castrate-sensitive prostate cancer, and 23 were castrate resistant. All patients had prior exposure to androgen deprivation therapy, ADT and 32 of them were currently under ADT at the time of this [inaudible 00:03:09]. We underwent DCFPyL PET/CT for all patients and we used [inaudible 00:03:20] software to assess PET quantitative parameters such as standard uptake value, number of lesions, tumor volume burden and total lesion PSMA. Correlations with PET parameters on PSMA values were evaluated as well as correlations with the ADT exposure.

This is a table with the patient's characteristics. More than half of the patients had prior prostatectomy or radiation and the remainder received androgen deprivation therapy alone or in combination therapy. Most of the patients had higher [inaudible 00:03:59] on the scores at diagnosis. 23 were castrate-resistant prostate cancer patients and 14 were castrate-sensitive with PSA values in a wide range.

At the time of the scan, most of the patients were under androgen deprivation therapy with a median duration time of 25 months. As results, we found that DCFPyL was able to detect metastatic disease in all patients with significantly more lesions detected in patients with castrate-resistant prostate cancer than castrate sensitive and with higher tumor volume burden for castrate-resistant prostate cancer patients, the standard uptake value, SUVmax in tumors was significantly higher in castrate-resistant prostate cancer patients than in castrate sensitive. These are some examples in my case of DCFPyL PET/CT into different metastatic prostate cancer patients.

The set of images on the left is from a patient of a 67 year old male with androgen-sensitive metastatic prostate cancer to the bone, PSA of 6.9, and DCFPyL [inaudible 00:05:24] demonstrate a very intense uptake in several DCFPyL-avid bone metastasis in the spine and in the pelvis, as we can see on the PET/CT images, with overall low tumor volume burden compared to the patient on the right.

The patient on the right is a 63-year-old male with metastatic castrate-resistant prostate cancer with multiple prior therapies and PSA of 134. Images show multiple DCFPyL-avid metastatic lesions in the bones and in the liver with high tumor volume burden. Both patients were under the influence of ADT at the time of the scan. And we were still able to identify lesions in both cases. We also found that PSA at the time of this scan correlated with total tumor volume burden for all patients and with the tumor uptake is to be matched for castrate sensitive prostate cancer patients. In patients with ADT at the time of the PSMA PET scan, PSMA tumor uptake was significantly lower for early castrate sensitive patients on short term ADT when PSA was lower than .2 compared to those with advanced disease and long-term ADT.

We may conclude that DCFPyL PET imaging was able to identify metastases in both castrate sensitive and castrate-resistant metastatic prostate cancer patients. In patients with advanced metastatic castrate prostate cancer, F-18-labeled DCFPyL demonstrated more lesions, higher tumor volume burden and higher PSMA PET uptake than castrate sensitive prostate cancer patients. For early castrate-sensitive prostate cancer patients on short-term ADT with PSA less than 0.2, the PSMA uptake was lower than the patients on long-term ADT. So we believe that the utility of PSMA targeted imaging in metastatic prostate cancer may depend on patient's castrate status an ADT exposure time. Thank you very much for your attention.

Alicia Morgans: 
Thank you so much for sharing that and thank you for doing this work. I think that these are precisely the questions that we're asking in the field because 18F‐DCFPyL has recently been approved now. So we are all anticipating integrating it into our treatment planning procedures as we're moving forward with our patients, particularly I think, as you mentioned in the biochemical recurrence setting, importantly, sometimes we have patients on hormonal suppression in that setting and sometimes not. So ensuring that we understand how the castration status affects the imaging, it's going to be very, very important.

Now, we talked a little bit before this interview, and I think one point that I would love to hear from you that you mentioned then is the utility of this type of study, which is really a single point in time versus a longitudinal study. This is really a nice starting point, but you mentioned that it might be really interesting for you and the team and for others to do investigations that look across time at patients to understand how expression of PSMA may change in how the utility at the imaging may vary, or at least to understand how we can best use imaging over time. What are your thoughts?

Esther Mena Gonzalez: As you may see from our results, we have a very small cohort of patients with metastatic prostate cancer. So we scan these patients only at one-time point, and this will be fantastic to increase the numbers and a longitudinal study with more patients and scan those patients over time to assess for the utility of ADT over time.

Alicia Morgans: 
Great. So I think that will be very interesting and I look forward to seeing your future work. Is there anything else that you want to share as an overarching theme about your findings here or the take-home message for the viewers?

Esther Mena Gonzalez: So for the viewers, we see from our results that the short term and long-term use of ADT, that didn't interfere in the interpretation of PSMA PET in patients with metastatic prostate cancer patients, because we saw lesions in all of our patients and with a wide spectrum of PSA values and with a wide spectrum of time from ADT-

Alicia Morgans: 
Very, very important. Was there anything else you wanted to add?

Esther Mena Gonzalez: This particular thing that we saw in patients with short term ADT and with PSA very low, .20, less than .20, those patients, PSMA PET, the SUV values and the uptake values is lower than the other patients of the other end of the spectrum and most likely is due to those patients receiving ADT are short term and responding to ADT most likely.

Alicia Morgans: I think those are very good points-

Esther Mena Gonzalez: [crosstalk 00:11:37] cohort of patients, of course.

Alicia Morgans: Of course, of course. Very good points and very important work. So interesting and I appreciate that you took the time to go through this with us today. I sincerely congratulate you and your team for the successful investigation and I look forward to seeing your work in the future. Thank you so much, Dr. Mena.

Esther Mena Gonzalez: Thank you so much.
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