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Neeraj Agarwal: Welcome to Dr. Mike Wenzel, to today's UroToday episode. Dr. Wenzel is a urologic surgeon in the Department of Urology in the University of Frankfurt in Germany. He presented quite intriguing results from the real-world experience of comparison of efficacy of cabazitaxel and lutetium-177–based radioligand therapy from a large database in Germany. So we would love to hear from Dr. Wenzel about the findings, and then we'll have some questions and answers. So welcome, Mike.

Mike Wenzel: Thank you for having me today. So I'm very pleased to talk about my findings regarding the real-world comparison of cabazitaxel versus lutetium-PSMA radioligand therapy today. And what we basically did was rely on the FRAMCAP database, the database we created several years ago, standing for Frankfurt Metastatic Cancer Database of the Prostate, sampling over 1,200 metastatic prostate cancer patients.

On the slide, you see the average patient being in the database roughly about 70 years, 50% of patients being high-volume disease according to CHAARTED criteria, a certain percentage of patients harboring ECOG status greater or equal to 2, currently a median follow-up of three years, and over 20 papers currently under review or published regarding the FRAMCAP database.

And when we looked into our comparisons of patients receiving the therapy in first- to seventh-line mCRPC, we gathered roughly 300 patients, of which 52 were receiving cabazitaxel and 82% lutetium-PSMA. Comparing baseline characteristics, we’ve seen that the baseline characteristics were more unfavorable in the lutetium cohort—being older or harboring higher rates of ECOG status greater or equal to 2.

Conversely, patients receiving cabazitaxel harbored higher median PSA or higher rates of Gleason score 8 to 10 de novo or high-volume mHSPC disease. Looking into our outcomes, firstly regarding the progression-free survival on the left side, we’ve seen that patients undergoing lutetium therapy harbored a significantly longer PFS outcome, 13 months versus 7 months, also very significant after multivariable adjustment.

On the right side, you can see the figure regarding overall survival. And you see a certain trend for better overall survival for lutetium patients, 17 months versus cabazitaxel patients, 15 months. And patients receiving both treatments sequentially have the best outcome. Afterwards, we also conducted sensitivity analyses to replicate a phase III trial and inclusion criteria such as the VISION trial or TheraP trial, and we almost saw similar results. Seen on the left side, the PFS outcomes were also 13 versus 8 months, then with a significant difference, unfortunately not significant after multivariable adjustment, and also kind of similar results for overall survival.

So we concluded that treatment with lutetium results in significantly better PFS outcomes for mCRPC patients. OS is numerically better, kind of comparable compared to cabazitaxel. Similar results were seen in the VISION or TheraP trial. And if possible, both treatments should be applied to our mCRPC patients. And we were very happy that this project was already published in the Journal of Nuclear Medicine this year.

Neeraj Agarwal: Congratulations, Mike, for presenting these data at the ASCO-GU 2025 symposium, and for soon-to-be-published manuscript. So we are looking forward to reading the manuscript and seeing the data in more detail. Let me ask you the first question first. What are those patients? Where are they seen? Are they seen at the university hospital? Or are they seen in the community, or a mix of that?

Mike Wenzel: Thank you for your question. And these patients are usually seen within our Department of Urology, treated there at the university hospital, and a certain amount are patients seen by outpatient urologists seeking our help and consultation.

Neeraj Agarwal: So these patients still have access to the University of Frankfurt urology service?

Mike Wenzel: Exactly.

Neeraj Agarwal: I’m asking because, first of all, it’s very impressive to see that patients are getting up to seven lines of treatments in metastatic CRPC, which is kind of unusual to see among those patients who are not really seen in a tertiary cancer center—so which was impressive. The second is, again, this is great to have such a data set. To be maintained, it must require significant time and efforts to maintain such a database, which has individual patient-level information with so many nuances that you can perform sensitivity analyses. You can actually replicate the trial design in a retrospective data set.

And that’s how we get to learn so much from this data set. As you mentioned, you have about 20 manuscripts, either accepted or submitted from this database. Coming to the conclusion, lutetium-177–based radioligand therapy seems to be superior to cabazitaxel from a progression-free survival perspective. Obviously, there’s a trend for overall survival, but the data are not large enough—the patient sample size is not large enough to inform on overall survival yet.

Did you take into account the delay in administration of lutetium-177? So there was an abstract presented at ASCO-GU by Dr. Swami and team that it takes about three times longer to arrange the actual administration of lutetium therapy to our patients compared to cabazitaxel. That’s number one. And that didn’t take into account the time, which it takes, at least in the US, to obtain a PSMA PET scan. So we have to obtain a PSMA PET scan first. And then we ask insurance companies to pre-authorize for lutetium therapy.

And that adds another period to that already long period when you are starting PSMA PET scan, then you are ordering a lutetium-177 treatment. And then you have to coordinate with nuclear medicine. You have to coordinate with other stakeholders, especially if a patient is not from within the town. If they are traveling, then you have to coordinate with other services to make sure the lutetium therapy is delivered on time. So how is the situation different in your setting from what we are seeing in the US?

Mike Wenzel: Very good point. We also have similar problems in Germany. And that leads to the point that we need closer cooperation with the nuclear department, I guess, in the future, because all those therapies will come in more, maybe also in the mHSPC setting at some time. So these patients are going to be seen by the nuclear department in the future.

And currently, we also have some situations in which we need to find solutions for the patients. And I totally agree that reimbursement and getting the right environment for the patient is challenging right now. But I guess we’re going to find ways. Because if you deliver cabazitaxel, you face similar problems if the patient is outpatient and needs to come to the hospital. So from that point of view, I guess it’s similar. But cabazitaxel treatment might be easier to administer because of the reimbursement and administration stuff.

So I completely agree with you. We have similar problems and things we need to take care of in Germany.

Neeraj Agarwal: So I’m glad to hear that we are facing similar issues. And it seems like the key to administering lutetium-177 therapy in a timely fashion is to closely coordinate with nuclear medicine and other referring physicians who are referring the patients from the community or from other sites where nuclear medicine facility or nuclear medicine expertise is not there.

Now, coming back to the data, you showed that lutetium-177 RLT was superior to cabazitaxel from progression-free survival. How big was the difference, just for the recollection for our audience?

Mike Wenzel: Yeah, it was five to six months in median, so quite a big difference in PFS outcomes.

Neeraj Agarwal: Did you select patients based on the VISION criteria, meaning the PSMA PET scan results should show PSMA uptake more than liver? Or was there a selection bias in terms of a higher SUV uptake being required before you included these patients?

Mike Wenzel: For sure, a certain selection bias cannot be ruled out here, since only patients with PSMA uptake were administered or were referred to our nuclear medicine department. So if the patient maybe didn’t have a PSMA uptake good enough for the radioligand therapy, they may have received cabazitaxel. So there’s a certain selection bias which needs to be accounted for in the interpretation of the results. But results were quite similar in the VISION trial or in the TheraP trial.

So we kind of tried to replicate this. And I guess it’s very convincing for treating oncologists or urologists, depending on which country you are in, that you see similar results within real-world evidence cohorts and also in prospective phase III trials, so that we can go to our oncologist or our urologist and tell them, these are our patients, which we are seeing each day, and these are the results of our patients. So I guess this is quite convincing.

Neeraj Agarwal: I agree with you. We are also looking into this in the large Flatiron database, which is the patient-level database in the US, and hope to present these findings in a meeting in the near future. But I agree with you. Your data are very much in line with what we have seen in VISION, what we have seen in the TheraP trial, even though it was a smaller trial compared to VISION. But again, very similar trends. Looks like, just for our audience, it is better.

The message is, it’s better to get lutetium-177 over cabazitaxel if both are available, but it may be even better to give both if possible. Is that correct?

Mike Wenzel: That’s correct. This is also a certain bias. If you receive both treatments, you are one of these patients responding well on the first treatment, or you have a good life expectancy. You don’t have complications or comorbidities, and so you’re going to receive a subsequent treatment as well. And as you already said, within our cohort, we included patients up to the seventh line of mCRPC. But what we’ve also seen is that within our database, the median therapy lines in mCRPC are 1 or 2.

So I guess we need to keep that in mind that not the majority of patients are receiving four, five, six therapy lines in mCRPC. And we need to find our way to expand those treatments for these patients.

Neeraj Agarwal: Thank you very much. So again, congratulations, Mike, for presenting this real-world comparison of cabazitaxel plus lutetium-177 PSMA radioligand therapy from a real-world database from the University of Frankfurt and the associated practices, showing that progression-free survival with lutetium-177 was quite remarkably longer than cabazitaxel. But the patients who did best were those who were able to receive both lutetium-177 and cabazitaxel. So thank you very much for taking the time to join us, and we look forward to seeing the full publication soon.

Mike Wenzel: Thank you very much for having me today, the opportunity to present my data—or our data of our research team—and the nice discussion.