ZUSDURI and the ENVISION Trial: A Non-Surgical Path Forward for Recurrent Bladder Cancer

For patients living with recurrent non-muscle invasive bladder cancer, the cycle of surveillance, surgery and recovery can take a steep toll on both body and mind. Long-term results from the ENVISION trial suggest that ZUSDURI (UGN-102), a chemoablative therapy administered through six weekly in-office instillations, may offer a durable alternative to repeated transurethral resections, with nearly 80% of patients achieving a complete response and many remaining disease-free for up to three years without maintenance therapy. To better understand what these findings could mean for patients in terms of quality of life, treatment burden and long-term care, CURE spoke with Dr. Sandip Prasad, vice chair of urology at Morristown Medical Center/Atlantic Health System.

Cure: For patients who have faced multiple bladder cancer recurrences and surgeries, how could a durable, non-surgical treatment option change their quality of life and long-term care experience?

Prasad: Urologists continue to better understand the impact both physically and mentally of having recurrence of bladder cancer on patients. In addition to progressive changes in lower urinary symptoms such as bleeding, frequency, urgency and pain that can be temporary or long-standing, there are significant psychosocial implications to a recurrence of bladder cancer. Treatments that minimize recurrence allow for increased intervals between cystoscopies and minimize the physical burdens associated with urologic interventions.

Many patients worry about repeated procedures and time spent in the operating room. What do these long-term ENVISION results suggest about the possibility of reducing the need for future surgeries?

For the almost 80% of patients that achieved a complete response of tumor eradication without surgery on ENVISION, the majority will continue to enjoy the benefits of a disease-free bladder for three years. These patients can avoid the operating room and TURBT and instead proceed with office-based cystoscopy at increasing intervals. We are studying the potential decrease in expected surgeries between patients managed with traditional management compared with UGN-102 and will hopefully have data to present soon.

The study found durable responses without maintenance therapy. What does that mean for patients who are concerned about ongoing treatment burdens, side effects or frequent clinic visits?

One of the very unique characteristics observed on ENVISION is that the durable disease-free result over years is achieved without maintenance. Six weekly in-office treatments three years prior eradicate tumor for over three years in most patients who underwent treatment — this result was particularly notable as the majority of patients enrolled in ENVISION had had a recurrence in the prior 12 months. The lack of repeated maintenance intravesical treatments (as is typically done with available chemotherapy and immunotherapy options in the adjuvant setting) provides a respite for patients and their families/support network from additional visits to support and provide maintenance care. As many of our bladder cancer patients are elderly, the burden of their healthcare requirements can be overwhelming. In addition, without the regular catheterization and instillations, many patients note that their voiding is "back to normal" in the absence of continued and repeated treatments over time.

As more bladder cancer treatments move into the office setting, what benefits might patients experience compared with traditional surgical management in a hospital or outpatient surgery center?

Treatments like ZUSDURI can be administered in the office without the need for general anesthesia, discontinuation of blood thinners or requirements for retention of intravesical treatment. This can be quickly and efficiently administered in a typical intravesical instillation clinic in their urologist's office rather than a potentially overwhelming operating room. It's a familiar location that typically doesn't require extensive preparation or instruction prior to each treatment. This can save time and effort and potentially decrease the reliance on support networks that may often be needed around the time of a surgical procedure. In addition, avoiding the need for pre-operative anesthesia clearance and pre-op testing like bloodwork or EKG can minimize the burden to patients around each traditional surgical intervention.

For older adults, who make up a large portion of the bladder cancer population, how could bladder-sparing and localized treatment approaches help preserve independence and everyday functioning?

The average age for bladder cancer patients is 75 years; this is routinely an older population with concomitant medical issues and concerns about preserving quality-of-life as part of their cancer journey. One of the most significant concerns I hear from my patients is that they are worried about the possible cognitive impacts of repeated anesthesia and the long-term implications of this. My elderly bladder cancer patients are often no longer driving and are bothered by requesting help from family and friends to get to appointments and treatments. In addition, there is a cumulative effect of bladder deterioration associated with repeated surgeries (with potential stricture or scarring) and treatments which often cause permanent changes in urgency and frequency. Concerns regarding incontinence and frequency can dominate the social schedule for patients, often limiting their independence due to concerns about having accidents in public.

What questions should patients with recurrent low-grade NMIBC ask their care team when deciding whether a chemoablative treatment like ZUSDURI may be appropriate for them?

Most patients with recurrent LG-IR-NMIBC are candidates for Zusduri unless catheter placement is difficult due to urethral stricture disease. It's important for patients to initiate and advocate for a discussion about the appropriateness of novel treatments like ZUSDURI to ensure they are receiving the optimal care for this chronic, life-long disease.

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