A Novel Imaging Modality, FAP Imaging for Patients with Bladder Cancer - Vadim S. Koshkin

October 17, 2022

Petros Grivas and Vadim Koskin discuss an investigator-initiated trial of imaging across solid malignancies. A novel way of imaging cancer. Fibroblast activation protein-α (FAP) is a transmembrane protein overexpressed on cancer-associated fibroblasts (CAFs), and instead of imaging cancer cells themselves, this images cells that are present in cancer. These scans label fibroblast activation proteins that are present in cancer-associated fibroblasts. This is an ongoing trial aiming to enroll about 80 patients across the board for solid malignancies, and in this discussion, Drs. Grivas and Koshkin focus on bladder cancer patients for this discussion. 


Vadim S. Koshkin, MD, Assistant Professor, Division of Hematology and Oncology, University of California San Francisco, San Francisco, CA

Petros Grivas, MD, Ph.D., Associate Professor, Clinical Director of Genitourinary Cancers Program, University of Washington, Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center.

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Petros Grivas: Hello! I'm Dr. Petros Grivas from University of Washington, Fred Hutchinson Cancer Center. I'm very excited to be at ASCO 2022, being in person after a long time of course, with safety measures. I'm also very excited to be here today with Dr. Vadim Koshkin, who's an Assistant Professor at University of California, San Francisco, UCSF. Vadim, welcome.

Vadim Koshkin: Thank you so much Petros for the opportunity to talk to you about this abstract and to see you in person again. Yeah.

Petros Grivas: It's great to be here and see you and so much going on at that ASCO meeting. And we'll ask you about your poster, that you're presenting. Great, really interesting work with the novel imaging in the field of urothelial cancer, the FAP imaging, the fibroblast associated protein, activation protein and cancer associated fibroblasts. And I would like to hear more about your abstract and how this novel imaging might potential have a role down the road.

Vadim Koshkin: Well, again, thank you for the opportunity to discuss this abstract here today. And again, the opportunity to meet in person again for first time in two years, since our last big ASCO meeting. I'm here today to talk about an abstract, that we are presenting with one of my colleagues at the University of California, San Francisco, Dr. Tom Hope. And I really want to acknowledge his role in really driving this research. This is an investigator-initiated trial of imaging across solid malignancies. So FAP scans, which is what we're discussing today is basically a novel way of imaging cancer. So, instead of imaging cancer cells themselves, this images cells that are present in the cancer. So, these scans label fibroblast activation proteins that are present on cancer associated fibroblasts. And it presents basically a new opportunity for both novel imaging and also potentially for Theranostics, though we won't talk too much about that today.

This is an ongoing trial, aiming to enroll about 80 patients across the board for solid malignancies, but I really want to focus on the bladder cancer patients for this discussion. Currently, 27 patients have been enrolled and we're enrolling in three cohorts. First cohort, is just a dosimetry cohort and then cohorts two and three respectively, are cohorts of patients with RECIST measurable metastatic disease, and then also patients at high risk for metastatic disease but who don't necessarily have RECIST measurable disease. And I want to highlight quickly the results that we have thus far, which really are I think quite promising and suggest that this could be a really novel way of imaging patients with advanced bladder cancer. So, thus far of the 27 patients enrolled, 24 had positive FAP uptake on scans. So, sensitivity of almost 90%. This includes eight of nine bladder cancer patients. Bladder cancer patients had the highest SUV uptakes.

Moreover, I should also say that most patients in the trial had FDG-PET scans that were paired with these novel FAP scans as well. And across the board for bladder cancer patients, the SUV uptake was considerably higher on the FAP scans then on the FDG-PET scans. Additionally, what we're finding is that many lesions that are not detected in FDG-PET scans, and of course not appear as normal size lymph nodes on conventional imaging are detected by FAP scans. And in certain cases, these lesions detected on FAP scans when biopsy confirmed actually even led to changes in clinical management. Again, a lot of these results are preliminary, which is why we're excited to present this initial abstract. And this is ongoing, but really suggest I think significant promise for this as a novel imaging modality for patients with advanced bladder cancer.

Petros Grivas: That sounds very exciting in novel imaging for sure. And imaging is definitely a modality we need to develop further in the field of urothelial cancer and bladder cancer, will help us with staging as you pointed out and ultimately to see whether we can impact treatment decisions and eventually outcomes. So in that context, my question to you is what are the next steps here? How can we further validate prospectively in the larger sample sizes exciting work and evaluate whether the incorporation of this novel imaging can have an impact in the more in the decision making, but also in patient outcomes? How will you go further to assess that?

Vadim Koshkin: Absolutely, great question. Well, the immediate next steps are of course to finish out basically enrolling this trial. Initially, this abstract is presenting an initial 27 patients. We're actually over halfway done with this trial by now, so it's certainly progressing. But again, the really exciting data from this trial among other malignancies has been in bladder cancer. And so, based off of this, we are planning a larger study focusing specifically on bladder cancer patients in the perioperative setting. So, patients who have muscle invasive disease and are intended to undergo radical cystectomy, and to see if there's a better way to essentially detect especially localized lymph node metastasis, which currently available scans there is much to be desired in terms of how well we're doing that prior to radical cystectomy.

Petros Grivas: It's a great opportunity. And again, we are struggling with an optimal clinical staging in bladder cancer, especially localized disease, and whether lymph node metastasis present can make a big difference in the management of a patient. So, I think evaluating perspectively this new imaging modality and see whether it has an impact in decision making and outcomes will be a big deal. And of course, I suppose one other question can be the ascertainment of the positive finding with the biopsy is another question and the practicality of that of course.

Vadim Koshkin: Yeah, absolutely. And that's of course, really the gold standard that we're seeking. In the current data set and the data presented in this abstract, we didn't cover that as much. But I will say that again, as I mentioned earlier, that there were several instances where lesions quiescent or really not detected on conventional imaging, but detected on FAP imaging were biopsied and confirming basically metastatic disease, which we would not have otherwise found. And this really changed the clinical decision making for a patient. So, a patient who would've gone to radical cystectomy instead was treated with systemic therapy for metastatic disease. But going forward, in the larger trial of course, this ascertainment will be addressed by essentially using the pathology results at the time of radical cystectomy as the gold standard. So, for instance pelvic lymph nodes detected on the scan, will essentially their pathology will be confirmed at the time of surgery.

Petros Grivas: And if you find that distant metastatic site at the time of FAP imaging, would that deter you from doing your radical cystectomy? Or how do you reconcile that? Or you still pursue radical cystectomy because not validated yet?

Vadim Koshkin: Yeah. Well this is an experimental scan, which is not yet validated, right? So, that's a great point. So, going forward, this is a decision that has to be made on a patient-by-patient basis. Certainly if there is high clinical suspicion I would say of metastatic disease, I mean you have to do what you think is best in your clinical judgment and probably attempt to confirm that with a biopsy. However, at this point I would say the scan being an experimental scan should not be used, should not be relied exclusively to make clinical decisions.

Petros Grivas: And that's a great point. I think for the audience I want to give the take home message is this a very exciting new research on a novel imaging modality, the FAP imaging for patients with bladder cancer is not ready for prime time yet, as Dr. Koshkin mentioned. It requires prospective validation and whether it can impact decision making and outcome. So, stay tuned in the future for more research by Dr. Koshkin and Dr. Hope and colleagues. More trials, so can keep that in the radar, again not practice changing yet but very promising for the future. Dr. Koshkin, thank you so much for your time here today and for your overall work in the field, that's very exciting.

Vadim Koshkin: Absolutely. Thank you so much for the opportunity to discuss this today and always appreciate this.

Petros Grivas: Of course, and thank you so much for your attention. Enjoy ASCO.