Dr. Amanda Nizam

be much more of a discussion with our patients as we get better control of the systemic disease.

And some of the upcoming trials, we're expecting readouts of more trials in the perioperative setting in muscle invasive bladder cancer in 2026, including Volga and then the EV304, which is EV PEMBRO versus GEMSYS in the cisplatin eligible population.

So that may give us an indication in terms of optimal number of EV patients.

pembro cycles in the perioperative setting.

And then also, Volga may help us answer a little bit about the contributions of the neoadjuvant and adjuvant phases, since that one does not have adjuvant EV in there, just the adjuvant immunotherapy component.

But the real question is, and this was discussed at the Euromigos live meeting, and I thought it was a really great point,

As we see more EV pembro move into the perioperative setting, and I think most of us expect that EV pembro in the cisplatin-eligible population will also be positive, what is the role of cisplatin eligibility anymore in bladder cancer, whether it's in the muscle-invasive or metastatic setting?

Okay, so the INVIGOR-010 trial was a phase three international randomized trial looking at adjuvant atezolizumab versus observation in patients with high-risk muscle invasive bladder cancer, which used the traditional high-risk definition of YPT2 to T4 or lymph node positive after neoadjuvant chemotherapy or P pathologic T3 to T4A or node positive without neoadjuvant chemotherapy.

So that trial did not meet its primary endpoint of DFS.

But when they looked at the ctDNA as an exploratory marker, they noticed that patients who did have ctDNA-positive disease benefited from adjuvant etizolizumab.

So that was used to develop the biomarker-driven Invigor 011.

And the Envigro-1-1 trial was a phase three international randomized trial that looked at that same population of high-risk muscle-invasive bladder cancer.

They could have either received or not received prior neoadjuvant chemotherapy.

And so they looked at two arms here.

Patients basically had, they were followed for up to 12 months post-cystectomy.

So those that were ctDNA negative were monitored on surveillance with scans every six months for two years and survival every six months for two years.

And ctDNA was monitored there.

Once patients turned ctDNA positive, they were randomized two to one to either a tesolizumab or placebo and then followed up.

And that was the primary analysis population.

And that is the trial that was presented at ESMO this year by Tom Powles and did confirm that giving atezolizumab in ctDNA-positive patients did meet its primary endpoint of DFS and OS, which is the secondary endpoint.