Q&A: Suzanne B. Merrill, MD, FACS, on treating high-risk NMIBC

Treatment selection in high-risk non–muscle-invasive bladder cancer (NMIBC) now reaches beyond BCG alone. Data from the POTOMAC trial (NCT03528694) support durvalumab (Imfinzi) plus BCG in BCG-naive disease. Options in the BCG-unresponsive setting also keep expanding, with no clear guidance on sequencing.

Suzanne B. Merrill, MD, FACS, a urologic oncologist at Colorado Urology, an affiliate of One Urology, spoke with Urology Times^® at the 2026 LUGPA Annual Meeting about how she approaches these decisions. She discussed patient selection for durvalumab plus BCG and how she sequences bladder-preserving therapies in BCG-unresponsive disease. She also covered which findings prompt a recommendation for radical cystectomy, the emerging therapies she is watching, and biomarkers with potential to guide treatment intensity.

This Q&A is part 1 of a 2-part interview with Merrill. In part 2, she discusses perioperative regimen selection, ctDNA, and the role of cystectomy alone in muscle-invasive bladder cancer.

This Urology Times Q&A has been edited and consolidated from a recorded interview to improve readability while preserving the substance of the original conversation.

Urology Times: For high-risk NMIBC, what guides your choice between BCG alone, BCG plus systemic immunotherapy, and early radical cystectomy?

Merrill: This [is a] very pertinent question, as now we have in the up-front setting not only BCG recommended but [also] a new combination, BCG and durvalumab, from the POTOMAC trial.

What just got read out at ESMO [the European Society for Medical Oncology 2026 Congress] was looking more at subgroup analyses of the POTOMAC trial and who may benefit more, and it looks to be [that] actually T1 high-grade patients are showing an even greater benefit than the whole subset of BCG-naive high-risk patients. So could that be a specific niche, very high-risk group [in which] we think about doing treatment intensification beyond just BCG?

I do believe a lot of things still need to play out. For the particular patient in front of you, is that patient really interested in treatment intensification? Are they willing to have the increased risk of adverse events with having also a systemic therapy in addition to BCG? So [there are] a couple of nuances still to look at and to talk to the patients about [who] are in front of you.

Urology Times: Which patients would you consider for durvalumab plus BCG?

Merrill: For BCG and durvalumab, I would consider looking at that combination therapy in very high-risk patients. So, your T1 high grade, maybe [one who] even has some other features like LVI [lymphovascular invasion], maybe some variant histology in there. A patient [where] you take that and do a repeat TUR [transurethral resection], they still have T1 high grade, and it’s a patient [who] only wants to bladder spare. That could be someone [where] you say, “Yep, what is my best, most intensive treatment I can give them?” It could be the combination, as long as they understand there’s an increased risk of adverse events.

Urology Times: In BCG-unresponsive disease, how do you select among bladder-preserving treatments?

Merrill: More and more treatments are coming into this space, and so it’s getting challenging to decide which agent to pull out when there’s no guidance on sequencing. A lot of us are using certainly patient factors, [such as] how is their bladder, [and] socioeconomic factors to help us decide, but [also] a lot of disease factors.

So, what agent were they on previously? That mechanism of action likely will cause us to change to a different mechanism of action. For example, if they were on a cytotoxic agent, say gemcitabine/docetaxel of late, then maybe we want to go back to an immune-stimulating agent, like Anktiva [nogapendekin alfa inbakicept] and BCG or Adstiladrin [nadofaragene firadenovec], and vice versa. Did they just come off BCG? Maybe we want to change to a cytotoxic agent using Inlexzo [gemcitabine intravesical system].

And then also their duration of response [on] their last agent. Was it a short duration, so a quick relapse? So, I think there are some disease components [that] inform us onto [the] next agent, as well as the patient factors.

Urology Times: Which findings should prompt a recommendation for radical cystectomy in BCG-unresponsive disease?

Merrill: It has to be individualistic, but [there are] a couple of key components. Each time a patient recurs and they’re already in [the] BCG-unresponsive space, before we’re cycling to [the] next agent, we want to be making sure we’re fully assessing the patient. CT urogram: Did we do a complete TURBT [transurethral resection of bladder tumor]? Maybe did we use enhanced cystoscopy, etc? Do we really know exactly [the] stage of the patient and if they’re localized?

Other factors upon which we want to pull [the] trigger for radical cystectomy sooner, rather than getting out [the] next card of treatment for bladder sparing, is if they’re recurring fast. Again, [it’s] that duration of response on these novel therapies. And then, is their disease getting worse in volume, and then also stage?

So, if you’re seeing someone go, for example, [from] just Ta high grade, BCG unresponsive, and now they’re developing CIS [carcinoma in situ] or maybe T1 features, or again, if that volume’s getting bigger, even if their disease might be localized, this should be a really hard discussion about that. Likely, it’s probably in their best interest to move to radical cystectomy before it’s too late.

Urology Times: Which emerging therapies or trial results could most influence NMIBC treatment decisions?

Merrill: [This is] still a completely exciting time in bladder cancer, and we’re so lucky [this] is just perpetuating.

The data coming out with combination therapies of cretostimogene and gemcitabine are very exciting, and CG Oncology is studying this combination in a number of disease stages of non–muscle-invasive disease and [is] showing some really good early results. That’s something to really look out for, is that combination therapy.

I think also interesting to look at is some of these novel delivery systems. In addition to combining agents together, [it] is about the delivery system and how we can get more savvy in terms of increasing [the] dwell time, and with Relmada’s agent, that’s something also to look out for. As we know, gemcitabine/docetaxel, again retrospectively, has shown [it] looks like it works very well. [The] BRIDGE trial [is] soon to read out, but how can we make that drug, or that combination of drugs, more easy for patients, [and] easy for practices too? And it could be through Relmada’s agent.

Urology Times: Which emerging biomarkers could help guide treatment escalation or de-escalation in NMIBC?

Merrill: I think there’s probably 3, I would say: Valar Labs and the Vesta Bladder BCGPredict; then, just to name the other two, the Decipher Bladder genomic classifier, looking at luminal versus non-luminal; and then your minimal residual disease, ctDNA [circulating tumor DNA]. Ultimately, all those tests I think are going to help us deliver more precision medicine.

Valar Labs, I think, is a great platform, computational histology AI, and [is] helping us try to predict and provide treatment insight. I’m hoping a lot of the trials [that] have already taken place are going to try to jump and use that platform, and actually retrospectively look at their data using that platform to see if there is a signal [that] can read out to help them show treatment insight for these industries’ particular drugs.

I think that would be remarkably helpful, especially in the BCG-unresponsive setting, where we have a number of agents, even a number of agents in the similar mechanism of action. All of us say, “Yes, we’re going to switch mechanism of action.” Well, if you have two pretty similar, then how do you decide between the two? So if we had a predictive biomarker like Valar Labs, [for] using some of these novel agents, [that would] be certainly helpful.

Urology Times: Where does the Decipher Bladder genomic classifier help in NMIBC?

Merrill: The Decipher Bladder genomic classifier, I think, is helpful as a prognostic marker. [Are we] not understanding, for example, a patient’s T1 true disease state? Do they harbor more aggressive signals [that] we should really be listening to? Should we move them to, for example, radical cystectomy? Should [we] be treatment-intensifying them if they’re BCG naive, for example, and they want to save their bladders?