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Ashish Kamat: So welcome. I have the pleasure of having with us today, Professor Jens Bedke from the University of Tubingen. He is a Professor of Urologic Oncology and Vice-Chairman there. Welcome and thank you for taking the time.

Jens Bedke: Yeah. Thank you, Ashish, for the invitation.

Ashish Kamat: My pleasure. We had an excellent bladder cancer session at the EAU this year. And one of the topics that you touched upon was the role of the surgeon in the multimodal management of patients with bladder cancer. So if you could elucidate a little bit as to your treatment paradigm for these patients, how you approach them, little tips for our listening audience, and viewing members.

Jens Bedke: Yeah. Thanks for the question. I think it's very, very important because treatment on metastatic renal cell carcinoma, metastatic bladder cell carcinoma is changing. And we know that cystectomy is the option which will provide the most benefit for our patients in the long term, but that we have to differentiate between different kind of patients and between different tumor types, and also between different stages. 

And while it was a great session where we discussed all the different scenarios and in the case, we especially focused on, we had a patient with a squamous cell carcinoma, which is one of the variants, which is well, not so frequent, but well, 10% of the patients present with this entity. And the question is, should these patients have neoadjuvant chemotherapeutic approach first? Or should they undergo cystectomy first and... Well, data for this approach is very limited, so we do not actually know what to do. And if we have a close look at clinical trials and retrospective case series, which are available, we know that a multidisciplinary approach is very much of importance for this patient population and the data available are subgroup analysis of the SWOG trial for the neoadjuvant chemotherapy. And at the end, we ruled out in the session that the most benefit for the patient is probably the variants and squamous cell carcinoma of the bladder [inaudible] that you make chemotherapy first, like a neoadjuvant approach. And then as a second step, take out the bladder by a cystectomy.

Ashish Kamat: So you mentioned variant histology. So of course there are many different variant histologies. There's micropapillary, there's squamous cell carcinoma, small cell carcinoma. When you're counseling these patients, do you factor in the percentage of their variant histology in the pathology report to make your treatment decisions?

Jens Bedke: Yes we do. And this is, I think very, very important if you have a pure variant or if you have a mixed type. And we usually tend, if it's a mixed type of a predominant component as a transitional cell carcinoma, that we stick to the treatment regimens of the transitional cell carcinoma. And just keep in mind that it's a subtype, which is in between, but with a smaller percentage. On the other hand, if you have a pure variant, especially for the small cell carcinoma, this is of utmost importance because here chemotherapy in our hands is very, very important to start first, and also to make a correct staging of the patients that you include, not only a CT scan of lung, abdomen, and the pelvis, but that you do not forget also to stage the brain.

Ashish Kamat: Yeah, no, that's a very important point because brain metastasis is rare with bladder cancer, but not so rare with small cell carcinoma. At our center, we have a prophylactic whole brain radiation paradigm for patients with advanced small cell carcinoma. Do you also use that at your center or do you have any other special tips for patients with small cell carcinoma?

Jens Bedke: Well, I'm aware of that. Actually, we do not do that as a prophylactic, the whole brain radiation, if there are no brain mets present at the initial stage. So we always have to keep in mind the timeframe of the patients, as you do not know at the beginning if the patient belongs to tumor biology is an early progressor, or is he slow progressor, even if it's the same entity of small cell carcinoma. So if the brain mets are not present we go to the neoadjuvant chemotherapy and then immediately to the cystectomy.

Ashish Kamat: There's a lot of discussion nowadays about molecular profiling of tumors and the TCGA and other similar projects, which are very important clearly. But do you think that they're ready for prime time use or still a research tool?

Jens Bedke: Well, I think there are different opinions about this. And first of all, I personally think that the paper from Robert [inaudible], the European Urology, is a landmark paper. And it's not only hypothesis-generating because it clearly demonstrated, even if it's in a retrospective fashion, that the TCGA subtypes of clinical relevance in bladder carcinoma, that you should differentiate between luminal and basal types. And the paper achieved the results that the basil subtypes are the most who will benefit from a neoadjuvant chemotherapy and that there are subtypes where we have, let's say lack of evidence, who will not benefit and who are probably prone to an immunotherapeutic approach, which will hopefully be observed in the perioperative IO trials, which will be starting or have already started for the neoadjuvant cystectomy and then the adjuvant IO approach. So currently, to come back to the question, while in clinical routine, TCGA subtyping is nothing we do on a routine basis because actually, prospective data for that concept is missing. And I would really appreciate to take that in the hand of the urological community to generate prospective database from this Robert [inaudible] paper.

Ashish Kamat: No, that's a very good point because, I think the data that we have to date is suggesting that it is real. The data is actually real, but it does need to be validated in a prospective manner before we can use it in the clinic. Let's switch gears just a little bit, and let's talk about your opinion on the role of surgery and chemotherapy in more advanced bladder cancer and the sequencing of the two. Which comes first and why?

Jens Bedke: Well, we have the concept that the metastatic bladder carcinoma, the main pillar of treatment is the systemic chemotherapy if the patient is eligible for cisplatin. If he's not eligible in the first-line setting, the so called cisplatin-ineligible, based on performance status or low GFR, that you have the immunotherapy of atezolizumab and pembrolizumab as an option. So first of all, the patient should have systemic treatment. And I do not think that you should consider a metastasectomy or a surgical approach as the most feasible way in this clinical situation of primary metastatic disease in metacarcinoma patients. So if you have started with chemotherapy and the patient is responding very well and belongs to the group of lots of longterm responders and disease is shrinking, and you have a partial response, and seems to be stable, then metastasectomy and surgery takes over and has its place in this treatment algorithm, that you make a metastasectomy and take out the remaining tumor, which at that stage should be at a limited volume. So either it's pelvic lymph nodes or isolated lung metastasis. There I think in this multidisciplinary approach surgery has its place.

Ashish Kamat: Do you think there's a window during which you need to observe the patient before you move to metastasectomy?

Jens Bedke: I think there is a window, but the window is individual. So I would not say the patient must be stable between six or 12 months with this disease. You should also take into account the morbidity of the patient, the frailty index, the age of the patient, and then you will make an individual decision. And of course, this must be in a multidisciplinary tumor board. So it's not an individual decision. It's a multidisciplinary decision taking into account also, the patient's wishes and his specific physical, but also psychological condition.

Ashish Kamat: No, that's important. Everything has to be personalized to that individual patient and situation. This has been a great conversation. In closing, if you would leave our viewers with maybe your take on the most important message in bladder cancer from this meeting today, what would it be?

Jens Bedke: Well, even if we have not covered the topic, I think urinary diversion and neobladder is a thing you could not talk often enough. It's very, very important to talk about the urinary diversion and the specific needs of the patient. I think the multidisciplinary approach is the second most important topic. And here you have the changes of the immunotherapy and the introduction of the immune checkpoint inhibitors in the systemic, and also the perioperative treatment of bladder carcinoma. So these are the three main goals which will concern us for the future and treating and delivering the best care for our patients.

Ashish Kamat: Right. Excellent points. Thank you very much for taking the time. It's been a real pleasure.

Jens Bedke: Thank you.