番茄社区

In this exclusive roundtable video from 番茄社区, three expert leaders in the field of bladder cancer discuss emerging data presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).

Moderator , of the Icahn School of Medicine at Mount Sinai in New York City, is joined by , of AdventHealth Cancer Institute in Orlando, and , also of the Icahn School of Medicine at Mount Sinai, in this third of four episodes, in which they discuss two studies that looked at bladder preservation.

Following is a transcript of their remarks:

Galsky: Hi, my name's Matt Galsky from the Icahn School of Medicine. Welcome to this roundtable on bladder cancer news from ASCO GU 2023. I'm thrilled to have with me Dr. Guru Sonpavde from Advent Health Orlando and Dr. John Sfakianos from the Icahn School of Medicine at Mount Sinai.

At ASCO GU this year we actually saw the results of two clinical trials seeking to advance a bladder sparing paradigm that's been a less commonly pursued bladder sparing paradigm. So traditionally, bladder sparing people think about tri-modality therapy, TURBT [trans urethral resection of bladder tumor] followed by concurrent chemoradiation.

But two trials were presented using a slightly different approach. One of those approaches involved chemotherapy plus immune checkpoint blockade. After that treatment was administered, patients underwent clinical restaging including cystoscopy, biopsies, imaging, urine cytology. And if all of that testing was normal, patients were considered to have a clinical complete response, and they could opt to have their bladders left intact and just receive maintenance immune checkpoint blockade. And in patients who didn't have a complete clinical response, cystectomy was recommended. And in that study we saw that if you achieved a complete clinical response, your chance of being metastases free was really quite high. And your chance of being metastases free with an intact bladder was quite high as well.

So some proof of concept for that approach, but certainly needs to be explored more extensively. Guru, there is another study called the -- somewhat similar although with some nuances. Can you tell us about that?

Sonpavde: Right, thanks Matt. So in the RETAIN study, this was a non-randomized study conducted by Fox Chase [Cancer Center in Philadelphia]. They gave dose dense MVAC [methotrexate, vinblastine sulfate, doxorubicin hydrochloride (Adriamycin), and cisplatin] neoadjuvant in muscle-invasive bladder cancer. And they elected to offer patients who had DNA damage repair alterations and a clinical complete response just active surveillance. So essentially there is data out there to show that patients who have somatic DNA damage repair alterations are more sensitive to cisplatin-based chemotherapy.

So perhaps clinical CR [complete response] in these patient's reflects true pathologic CR. And remember, we really cannot have pathologic CR without doing a radical cystectomy. So what the investigators were trying to do is in patients who have a therapeutic vulnerability and have clinical CR after neoadjuvant chemo, can we spare these patients radical cystectomy?

So these patients were surveilled, and it's not a big study. The overall study was around 70 patients. About half of those had a clinical CR, and they were offered active surveillance.

And at the end of the day the initial data from a couple years back appeared promising, but it looked like in the recent update they actually did not meet the metastasis-free survival bar they had hoped for, which is I believe a lower border of 95% CI of around 62-63%. So in the patients who are on active surveillance, which is actually less than 30 patients, so small dataset, so that's the caveat -- in this dataset around a third of patients actually recurred with metastasis. And actually most of these metastatic recurrences also had bladder recurrences. So that is a little bit worrisome in the sense that, there's a lot of metastatic recurrence, but maybe we can salvage some of these patients, if we have caught them early, with a cystectomy.

So at the end of the day, I feel that this paradigm is challenged by suboptimal clinical staging. We need better clinical staging to be able to determine whether the patient has truly had a nice response to the neoadjuvant chemo. Perhaps ctDNA [circulating tumor DNA] and urine tumor DNA is one way to go in that direction.

Galsky: So we have these two studies which were similarly designed, but with some nuances in terms of patient selection and the actual treatment administered. The follow up is a little bit different too. And whether or not the immune checkpoint blockade is making the difference in terms of those higher rates of metastases in one study versus another, I think we'll need to see with longer follow-up. But they do seem to be a little bit different in terms of the readout so far.

John, what do you think about this approach as a surgeon? What do you think about the fact that we know that path CRs can be achieved in some patients with TURBT alone? And is there actually a way to identify the patients with biomarkers who might just be able to have a TURBT for muscle-invasive bladder cancer?

Sfakianos: Yeah, that's a a great point. So, I'm a huge proponent of this approach. While I do think that the surgery has evolved drastically over the years with minimally invasive approaches, improvements in ERAS [enhanced recovery after surgery] pathways, so it's not as morbid as we remember it to be. Patients do recover quicker, they can get adjuvant treatments faster, so forth and so on. I do think that if we can identify a really good bladder sparing approach that has saved the patients with good quality of life post-treatment, then I think that that's what I would strongly push for my patients.

The main issue is to just echo again, is that we don't have really good clinical markers and/or imaging techniques to be able to truly identify those path CRs clinically. So whether it's urine ctDNA, plasma or systemic ctDNA, we're going to need something better to be able to identify those patients.

And to just echo what we just mentioned a little while ago, I do think that the maintenance therapy, sort of prolonged therapy here after the initial sort of the more aggressive therapy is what makes the difference between these two groups. And especially something like an immunotherapy where we may be able to develop some memory, so if these cancer cells start to show up again, our immune system can actually target them. I think that to me, just looking at the RETAIN trial and looking at your trial, Matt, that's the big difference, that there was that maintenance therapy afterwards.

Watch episode one: Updated Results on Adjuvant Immunotherapy in Muscle-Invasive Bladder Cancer

Watch episode two: Latest on Neoadjuvant Immunotherapy in Muscle-Invasive Bladder Cancer

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