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Ashish Kamat: A warm welcome to all of you to the UroToday Studios. I'm Ashish Kamat, Professor of Urologic Oncology at M.D. Anderson Cancer Center in Houston, Texas. We're live in San Francisco at ASCO-GU '25. It's a pleasure to welcome all the way from Germany, Professor Jens Bedke, who is here today. And he's going to share with us insights on the situation with BCG and the global shortage and everything to do with bladder cancer. So welcome, Jens.

Jens Bedke: Hey, thanks, Ashish. It's a pleasure to be here, live here in San Francisco, talking about non-muscle invasive bladder carcinoma and BCG treatment. Also, of course, BCG shortage. And we are presenting a poster tomorrow in the congress where we did a global survey of more than 1,900 patients—1,900 patients—which were interviewed between June and December 2023.

And they were having high-risk non-muscle invasive disease. And we captured some data on these, specifically if they received BCG treatment. And the result was, one of the main results is that only 2/3 are treated with BCG. I think this is quite interesting because I think you share my opinion that BCG is, well, the cornerstone of treatment in high-risk NMIBC.

Ashish Kamat: Yeah. No, I mean, and studies such as yours that look at what's happening across the globe are very important because one of the things we hear from our European colleagues and friends is that there's no shortage in Germany, right? Medac produces BCG, but we have a shortage here. So could you explain, were there regional differences in the receipt of BCG?

Jens Bedke: Yeah. One of the results is regional differences. And I totally agree. From my perspective in Germany, we don't really have a BCG shortage. We had that, like, two or three years ago. And they were only able to prescribe four doses, and then we had to re-prescribe. But at the end, every patient who needed BCG got BCG.

But we observed regional differences also within Europe, but also within the US. Canada had some patients, and they had BCG shortages up to 70%. And so I think it's an issue. And it's also an issue that the BCG strain you're using—sometimes you have to shift the strain. And we all know about the strains, that there are different strains, different efficacies.

Ashish Kamat: Yeah, and that brings up a good point. So currently, what strain are you using in your institution in Germany?

Jens Bedke: Usually we are using the BCG, the Medac strain, which is widely used in Germany. We have some access to the TICE, which I think is mainly used here in North America, but it's rare in Germany. I think it's more in the US.

We don't have access to the Tokyo strain, to be honest. Sometimes the Danish strain. Yeah, that's it.

Ashish Kamat: So when we see these patients now enrolling on studies for BCG-unresponsive disease, the definition was proposed to the FDA based on the data in the US—single-arm studies, BCG-unresponsive, you don't need a control arm. But that clearly was based upon the historic results with, for example, TICE BCG.

Do you have any sense, in your experience, your patients in Germany that are being treated with the Medac strain, for example, how do they fare compared to historic controls and historic response rates? Are you noticing any anecdotal differences?

Jens Bedke: Oh, I think it's a difficult question. And I'm not sure if there is data on the BCG unresponsiveness in relationship to different BCG strains which have been used in this treatment. I think from the clinical perspective, we do count the patients as BCG refractory as yes or no.

And always consider early cystectomy in these patients because, if compared to the US, we do not have the salvage strategies. For example, pembrolizumab is not approved in this indication in BCG-refractory patients. And we all know that the definition of BCG being BCG refractory has evolved a little bit. And also the question, shall we do a re-induction of the BCG, for example.

But getting back to the abstract or to the poster presentation, there was also one interesting result: the duration of BCG was very varied. So, to make it easy, one-third just received one year, another third received two years, and there was a final third which received up to three years of BCG. So I think one of the problems of BCG is also it's not really defined how long the maintenance phase should go.

Ashish Kamat: Yeah. And I think that's another important point, because the guidelines always state, do the maintenance—the induction and the maintenance—up to three years. And because of shortages, we've actually made recommendations in the US, for example (and I've done work, of course, with the EAU) saying that in the lesser-risk patients, you can do induction and up to one year of maintenance, and in the patients that are higher risk, you should try to push it to three years. Did you get any sense from your global survey as to whether people were using these selected maintenance durations based on shortage? Was there any clue in there?

Jens Bedke: Well, we did not correlate the patient with shortage or with a reduced use of BCG in terms of the efficacy and the refractory disease. So this was not part of the result. But it's an interesting idea to analyze that.

We observed, as mentioned, that patients were underdosed or that the dose was modulated due to the shortage issue. On the other hand, well, what shall we do with these patients who experience an effective shortage and are getting refractory and are relapsing?

And I think this clearly points out that they need other strategies. Maybe we also need strategies in combination of checkpoint inhibitors—BCG plus checkpoint inhibitor. As we know, there are a lot of trials ongoing. We got one press release of a positive trial of the CREST trial, which is positive according to the press release. So it's a field which is moving, I think.

Ashish Kamat: Yeah, no. And again, with all these BCG plus IO trials, the readouts have been delayed for years. They were supposed to be read out two years ago, three years ago. But the events on the BCG arm have been very low, we all suspect, because BCG is so effective nowadays. So it'd be interesting to see that it's positive, but how positive it is. And let me put you on the spot a little bit. If it's positive, which we expect it to be, in your opinion, when you're counseling your patients, what differential benefit would you want to see of BCG plus atezolizumab to make up for the toxicity of a systemic agent?

Jens Bedke: I think we will have to wait until we see the results to clearly answer this question. As far as of now, we only know that it is positive, according to the press release which was published. But a detailed discussion I think must be done when the data is out in the public domain.

Ashish Kamat: But hypothetically, let's ignore the study and let's say hypothetically BCG has an 80% two-year disease-free survival. Would you want to see BCG plus IO at 90, 85? What would you as a clinician like to see there?

Jens Bedke: Well, this brings us a little bit to the character of high-risk non-muscle invasive bladder carcinoma. I think we have two aspects: it's the relapse and the progression of disease. And that the high risk is defined as T1 high grade, but also incorporating CIS. And of course, what we do not want to have is patients progressing—progressing to metastatic disease.

We do not want to have patients progressing to T2 or even to T3 tumors, initially starting from a T1 or a CIS tumor. The clinical need which is there is the delay, but the decrease of progression. And of course, from the economic aspect side, it's the question, can we reduce the rates of relapses? Because every relapse means a TURBT. Every TURBT makes a scarring on the bladder. And we all know if a patient has had, like, five, six, seven TURBTs, the bladder capacity, the volume of the bladder, shrinks. The bladder scars. So there's also adverse changes within the bladder due to the multiple relapses which could occur.

Ashish Kamat: Absolutely. No, that's a great point. Coming back to your abstract, and just in closing—any closing thoughts for the audience? Where are you going to take the data that you have, and what are you going to use it for?

Jens Bedke: I think we shall use it that BCG is an issue, a BCG shortage is an issue—that the effective treatment time is an issue. So that we need the maintenance for the two years; patients should not be underdosed, which we observed. And that only 2/3 of the patients effectively received BCG. There was 1/3 of patients who did not receive BCG in this high-risk situation. And I think we must point out that there are patients in real-world practice not receiving the guideline-recommended therapy.

Ashish Kamat: Yeah. No, that's an important message for people to recognize, because clearly we have to do what's best for our patients. And hopefully the BCG shortage will be a thing of the past once the companies have more production capacity.

Jens Bedke: Definitely.

Ashish Kamat: Jens, thank you again for taking the time. Always a pleasure.

Jens Bedke: No, thank you.