Joep de Jong: Yeah. So first of all, first, Kamat, it's good to see you again. Thanks to the GU ASCO and UroToday team for doing this interview with you. The data that we are discussing are on the Decipher bladder biomarker, which is basically originally designed for muscle-invasive disease. But when we did one of the studies early on in 2019, we basically evaluated a cohort of patients that had either T1 non-muscle-invasive disease or T2 muscle-invasive disease by clinical staging. And then a subgroup of patients within this setting, they undergo radical cystectomy without neoadjuvant chemotherapy. I guess for T1 disease, that makes sense. For T2 disease, it is guideline recommended, but some still opt to not undergo it. And then in terms of pathological staging, we found that the luminal, non-luminal distinction by the Decipher Bladder Classifier enriched on the non-luminal site for patients that showed pathological upstaging at the radical cystectomy specimen. So basically means that if you're non-luminal T1 disease, you get a radical cystectomy, you're more likely to be upstaged to already muscle-invasive disease or sometimes even lymph node involvement.
And we did that in two consecutive studies. So the first one was in 2019. The other one was a little bit later in 2025. And then the curiosity around this marker used in a T1 setting basically led us to contact the bladder cancer prognosis program in the United Kingdom. So all credits for this study and these results go to them like the PIs are Richard Bryan and Doug Ward. And they allowed us to analyze samples from this prognosis program, which was a population-based registry, analyzed the baseline samples from the high-risk NMIBC cases. And then we found that in a treatment setting where they got treated conventionally, so not with radical cystectomy, but with BCG, and if there was BCG shortage intravesical chemotherapy, and we found that on the long term, so median follow-up of more than five years, the Decipher classification at baseline was significantly prognostic for overall survival outcomes and progression survival outcomes. And not so much for the recurrence-free survival outcomes, which is again, something that should be taken into account when counseling the patients for escalating therapeutics.
Ashish Kamat: I think that's an important point that you make and that it finds out, because if you look at most of the recent studies, event-free survival, if you look at the CREST data or the POTOMAC, they look at recurrences. And yes, recurrences are important to our patients, don't get me wrong, but what really truly matters is the progression. And other than outside of clinical pathologic features such as grade, stage, the very high-risk classification, for example, there has not been that much that has allowed us to identify the progression events. So share with me a little bit more deeper data into the actual power of the test to identify those progression events and what you did when it comes to the very high-risk cohort and how you sub-analyze that.
Joep de Jong: Yeah. Yeah. So again, those are very good points. I think, as you just highlighted on the clinical-pathological factors, as we know by now, we are able to dictate a very high-risk group. And I think what this data shows is that yes, we do see slight separation of the curves, and therefore, I mean that somewhat the very high-risk patients did show more progression, but there was no significant association at baseline. I think where the molecular marker comes in handy is that it somewhat outperformed statistically in terms of predicting the progression, but I think where it comes in important is not that we have to compete with clinical variables, but the additional data point, having this molecular marker suggesting a predictive performance for progression events could come in handy, especially within the very high-risk group, because according to the EAU guidelines, this is a group where we should consider escalating therapeutics based on radical cystectomy for T1 disease. And therefore, I think having the biomarker in conjunction with the clinical-pathological factors could counsel intensification of the treatment in this treatment setting.
Ashish Kamat: Yeah. I think when you're focusing on the very high-risk group, Niyati Lobo who's from the UK, spent some time with me and she showed that in treated patients, when you give them appropriate BCG treatment, the progression events go from the proposed 40% down to about 16%. So treatment is really effective, and that's been shown again at a poster that's going to be presented here and others. So let me ask you, what was the percentage progression and what was the hazard ratio between your marker positive, negative when you're looking at this very high-risk cohort?
Joep de Jong: So, Professor Kamat, this is a very interesting question. I think it's fair to say that the progression events, as you just illustrated, were relatively low, at least way lower than according to what the guidelines state nowadays. It's mainly because we do better in adequate BCG treatment, which is something you've been mostly involved in too. I think the clinical progression events also included consolidating to radiotherapy or radical cystectomy for BCG-unresponsive disease. And there were 40 events among the 259 patients included in this analysis. And then in terms of hazard rates, it was, in the univariable analysis, 3.4 times more likely to get any of those clinical progression events if you were non-luminal, than compared them when you would've been classified as luminal on the baseline clinical sample.
Ashish Kamat: Yeah. And again, I think it's really important for us now to recognize that the patient cohorts we're seeing today are different from the patient cohorts that we were seeing 10 years ago, 20 years ago, 30 years ago when I started, partly because of improvements in TURBT, cystoscopy, recognition, but also markers such as this. This is, in many ways, a retrospective cohort, but treatment decisions might have been informed by many different factors. I think data such as this is another factor that we should consider and use when we're counseling patients, like you said. And as you mentioned, and we were chatting earlier about the cysto data where some patients might actually prefer to have a radical cystectomy, and this might help them make their mind up sooner. So again, congratulations on the poster, on all the work that you've done. Like I said, really pleased to see everything that you've done at an early stage and thanks for taking the time.
Joep de Jong: Thank you very much. Yes.