Integrating chemoablation into everyday NMIBC practice

At a recent Urology Times Clinical Forum in Troy, Michigan, urologists and advanced practice providers convened to discuss the evolving management of non–muscle invasive bladder cancer (NMIBC), with particular focus on intermediate-risk disease and the emerging role of chemoablation. The conversation, moderated by Brian D. Seifman, MD, highlighted practical decision-making, patient case discussions, and the integration of new intravesical therapies into real-world practice. Seifman is a partner of the Michigan Institute of Urology.

This summary was generated by artificial intelligence and edited by humans for clarity.

Defining intermediate-risk disease

The discussion began with how clinicians define and stratify intermediate-risk NMIBC in daily practice. Participants acknowledged that “intermediate risk” represents a broad and often ambiguous category, encompassing both patients with recurrent low-grade tumors and those with multifocal disease. Differences between legacy grading systems (Grade I–III) and the current dichotomy of low vs high grade were noted, with some pathologists still using outdated terminology that can complicate treatment planning.

Panelists agreed that intermediate-risk disease typically includes patients with multifocal, low-grade Ta tumors; solitary tumors larger than 3 cm; or recurrences within 1 year. These cases warrant active treatment rather than observation alone, although select low-volume recurrences may still be managed conservatively depending on patient comorbidities and preferences.

Managing positive cytology with negative cystoscopy

A frequent clinical dilemma discussed was how to manage patients with positive urine cytology or FISH but negative cystoscopy and imaging findings. Strategies varied among participants. Some perform close cystoscopic surveillance every 3 months, whereas others pursue blue light cystoscopy or random bladder biopsies to identify occult lesions.

Opinions on blue light cystoscopy were mixed. Several clinicians found it useful for detecting subtle recurrences, particularly at the bladder dome or in areas of prior resection. Others cited false positives, patient discomfort, and logistical barriers such as scheduling, equipment costs, and staffing needs. Reimbursement concerns and availability also limit its use in some community settings.

Overview of intravesical options and new agents

From there, the conversation shifted to an overview of available and emerging intravesical therapies. Traditional agents such as BCG, mitomycin, and gemcitabine remain central to care, but the panel noted that new drug delivery technologies are expanding the field.

Two agents drew particular attention: mitomycin for intravesical solution (Zusduri) for recurrent low-grade, intermediate-risk NMIBC, and gemcitabine intravesical system (Inlexzo; formerly TAR-200) for adult patients with BCG-unresponsive NMIBC with carcinoma in situ, with or without papillary tumors.

Cost and accessibility remain significant concerns. Participants noted that pricing for some novel intravesical systems can reach tens of thousands of dollars per course, posing challenges for both institutions and patients.

Case 1: Initial low-grade disease and recurrence

The first case centered on a 63-year-old man initially treated for a single 2-cm low-grade Ta tumor with transurethral resection and 6 weekly instillations of gemcitabine. After remaining disease-free at 3 and 6 months, he presented with multifocal recurrence at 9 months, now classified as intermediate risk.

The group agreed that retreatment with intravesical chemotherapy—either gemcitabine or mitomycin—was appropriate. Although BCG was mentioned as an option, panelists pointed out that shortages and lack of evidence for superiority in low-grade disease often limit its use in this population. Many favored gemcitabine because of its favorable tolerability profile, ease of use, and low cost.

Mitomycin for intravesical solution and chemoablation

The panel then examined data supporting mitomycin for intravesical solution. In the ENVISION trial (NCT05243550), 240 patients received 6 weekly instillations of mitomycin in a reverse-thermal hydrogel formulation that solidifies in the bladder, prolonging drug dwell time. Complete response was achieved in roughly 80% of patients at 3 months, with approximately 80% of responders remaining disease-free at 1 year.

Adverse events were mostly mild to moderate, including dysuria, urgency, and hematuria, though 14% experienced grade 3 or higher events and approximately 3% developed urinary retention.

Participants described mitomycin for intravesical solution as a meaningful step forward for selected patients, particularly those with recurrent disease who wish to avoid anesthesia or are poor surgical candidates. However, they also raised practical questions about patient selection, histologic confirmation before treatment, and durability beyond 1 year. Some clinicians felt that for small-volume recurrences, a repeat transurethral resection of the bladder tumor (TURBT) may still be simpler and more cost-effective than a 6-week chemoablation course.

Using chemoablation in real practice

Panelists discussed how they might incorporate chemoablation into clinical workflows. Ideal candidates were described as older adults on anticoagulation, patients with anesthesia risk, or those who have “TURBT fatigue” after multiple resections. Confirming pathology with an office biopsy before initiating treatment was viewed as critical to ensure that no high-grade component is missed.

The logistics of delivering mitomycin for intravesical solution can be complex, requiring prior authorization, coordination with pharmacy services, and patient education about repeated catheter-based instillations. Some patients, especially those who experienced discomfort during prior intravesical therapy, may prefer a single surgical procedure over multiple office visits.

Case 2: Recurrent disease in a female patient

A second case described a 68-year-old woman with a history of low-grade Ta disease who recurred after gemcitabine induction, presenting with several small lesions at 1 and 2 years. The panel viewed chemoablation as an appropriate consideration for this multifocal, low-grade recurrence, particularly given the patient’s desire to avoid additional surgery.

Smoking history was discussed as a key contributor to recurrence risk, prompting several clinicians to recommend intensified follow-up with cystoscopy every 3 months. Participants noted that counseling on lifestyle factors remains an important but often underemphasized aspect of bladder cancer management.

Surveillance and maintenance strategies

Participants shared a range of follow-up practices. Most perform cystoscopy every 3 months during the first year, every 6 months in the second year, and annually thereafter if no recurrence occurs. Urine cytology and upper tract imaging are used selectively, depending on risk and symptoms.

Maintenance therapy remains variable. Some clinicians favor no maintenance for low-grade disease, whereas others apply “BCG-style” schedules with monthly or quarterly gemcitabine instillations. Fatigue and diminishing adherence over time are common, leading some to use noninvasive monitoring assays such as Cxbladder to support surveillance, though reimbursement limitations have curtailed widespread use.

Case 3: Managing early recurrence

In another scenario, a 68-year-old man experienced multifocal recurrence less than a year after completing gemcitabine induction. Most panelists recommended switching agents—either to mitomycin or mitomycin for intravesical solution —rather than repeating the same regimen. If recurrence occurs after a longer disease-free interval, such as 15 months or more, reinduction with the same drug may still be reasonable. As one clinician summarized, “If you fail early, change the mechanism.”

Future directions and cost considerations

The panel concluded with discussion of ongoing studies and emerging therapies. The ATLAS trial (NCT04688931) comparing mitomycin for intravesical solution alone vs resection plus mitomycin for intravesical solution demonstrated similar outcomes, reinforcing the concept of chemoablation as a non-surgical alternative for selected patients. Additional pipeline agents—including UGN-103, Inlexzo, and gene therapy approaches such as adenoviral vectors—are expected to further expand the NMIBC landscape.

However, participants emphasized that cost will remain a limiting factor. Prices for many newer intravesical therapies can exceed $20,000 to $60,000 per dose, raising concerns about access and payer approval. Despite these hurdles, clinicians expressed optimism that expanding treatment options will ultimately benefit patients with recurrent NMIBC.

Conclusion

The Troy discussion underscored that chemoablation is emerging as a valuable addition to NMIBC management, particularly for patients with recurrent, low-grade, intermediate-risk disease who wish to avoid surgery. Mitomycin for intravesical solution offers a novel outpatient approach, though questions remain regarding long-term durability, patient selection, and cost-effectiveness.

For now, gemcitabine remains a reliable and accessible standard, whereas new agents broaden the treatment toolkit. The consensus among panelists was clear: individualized therapy—guided by pathology, recurrence risk, and patient preference—will continue to drive optimal outcomes as the field of NMIBC evolves.