Marie-Pier St-Laurent from Vancouver, urologic oncologist, and David Anderer, an urologist from Vienna, Austria, discussed the role of ctDNA in urothelial cancer research. Dr. St-Laurent explained that ctDNA can be used in tumor-informed or tumor-naive approaches, with tumor-informed approaches using tumor tissue sequenced on platforms like whole genome or whole exome sequencing. A liquid biopsy is then performed on blood to identify if the disease is detectable in the blood system. Dr. Anderer also mentioned that ctDNA can be used as a biomarker for tumor burden in prospective phase three trials, such as Vigor trials. Dr. St-Laurent mentioned a trial called Neo-BLAST, which will incorporate ctDNA in patients with muscle-invasive bladder cancer. Patients will undergo standard of care, neoadjuvant chemo, or new neoadjuvant therapy, followed by ctDNA before and after the therapy. Non-responders will undergo active surveillance or bladder treatment, while those with positive ctDNA or MRI will receive usual care. The trial aims to detect early recurrence and offer next-line treatment if needed.
Transcript
Interviewer
Ladies and gentlemen, today and welcome at the EAU 25 in Madrid, Spain. My name is David Anderer, urologist from Vienna, Austria. And it’s my distinguished pleasure to welcome today with us Marie-Pier St-Laurent from Vancouver, urologic oncologist. Thank you very much for being with us today.
Dr. Marie-Pier St-Laurent
Oh, thank you for having me.
Interviewer
So, you are involved in a broad spectrum of research in urothelial cancer and specifically now in ctDNA. ctDNA is getting popularity, we hear a lot. Can you maybe explain in a couple of sentences to the broad audience, what is a ctDNA?
Dr. Marie-Pier St-Laurent
Sure, I can do. Uh, I have to disclaim, however, I’m not a genomics, you know, scientist. There’s a lot of people in Vancouver, Alex Wyatt, uh, who does a lot of ctDNA in our field, so I have to give, you know, them the rewards, I’ll say. So, in short, ctDNA, uh, there’s different platforms. You can have a tumor-informed, tumor-naive approach. Um, but if we look in the stage of not metastatic, so more localized disease, what we often see is tumor-informed approach. Um, so we will use a tumor tissue that gets sequenced on different platforms, target panel, or it can be a whole genome, whole exome sequencing, and you do a target panel of a signature for specific for the patients. And then on your blood draw, you’ll be doing a liquid biopsy to look for that signature and which will be your tumor kind of marker. So that way you can repeat measurement to try to identify if there’s that disease detectable in the blood system.
Interviewer
Excellent. So, very clear and we have seen, uh, ctDNA used as a biomarker for tumor burden in some prospective phase three trials, like in Vigor trials. What are now the next steps? Where can we also apply the ctDNA, maybe going one step before the metastatic disease?
Dr. Marie-Pier St-Laurent
Yeah, exactly correct. So there’s one trial I’m uh I’ve worked in, I design and I’ll will be enrolling in British Columbia, uh, in Canada soon and I’ve worked with this with Peter Black. So the trial is called Neo-BLAST, in which we’ll incorporate ctDNA as well. Um, so this trial is for patients with muscle-invasive bladder cancer will go for standard of care, uh, neoadjuvant chemo or, you know, whatever new neoadjuvant therapy will be allowed. Uh, and then we’ll do ctDNA at before the starting of the neoadjuvant therapy and after the completion. So at the time of a restaging to try to detect complete responder. Uh, so in this Neo-BLAST trial, we’ll do ctDNA of tumor-informed approach with bladder MRI, and then a repeat TURBT and bladder biopsy. And those who will have negative results, uh, will then be um, go into randomization uh to active surveillance or bladder treatment in the form most likely of chemo-radiation. The non-responders, so those with positive ctDNA or positive MRI will go for usual care with cystectomy. Uh, so that’s a way we’ll be incorporating ctDNA in the restaging following neoadjuvant therapy. And we’ll also have ctDNA in the surveillance. Um, so we’ll do 3, 6, 9, uh 12 months and, you know, a year and a half and two years measurement to try to detect early recurrence and, you know, offer a next-line treatment of, you know, IO if if needed.
Interviewer
So great. Thank you very much for sharing this with us. ctDNA is a step forward in the precision medicine. It’s coming probably to stay. Let’s see how it will evolve and thank you and have a nice congress.
Dr. Marie-Pier St-Laurent
Yeah, you’re welcome. Thanks.
