When to Consider Intravesical Therapy Versus Chemoablation in NMIBC

A roundtable discussion, moderated by Christopher Wallis, MD, PhD, FRCSC, focused on patient selection and treatment considerations for non-muscle invasive bladder cancer, including recent data from SUO 2023. Dr. Wallis was joined by Sia Daneshmand, MD; Piyush Agarwal, MD; and Sima Porten, MD, MPH.

In the next segment of the roundtable series, the panel conclude with their thoughts on considerations for TURBT and intravesical therapy versus chemoablation, as well what further trials are needed in the intermediate-risk space to change the treatment paradigm.

View other segments from this roundtable.

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Dr. Wallis: You discussed the importance of monitoring for progression. This brings us back to our earlier conversation. How crucial is repeated pathological assessment for tracking grade progression? Are there specific cystoscopic findings that would deter you from pursuing an ablative approach, prompting a return to the operating room?

Dr. Agarwal: Surveillance is a significant aspect of my approach for these patients. During cystoscopy, we conduct a bladder wash, extracting samples directly from the tumor area. Our cytopathologists analyze these samples for high-grade cells. If the results are negative for high-grade cells, I’m less concerned. However, any indication of high-grade cells or atypical findings may lead me to consider a formal transurethral resection of bladder tumor, especially if there is tumor growth or an increase in the number of tumors. Negative wash results often allow me to continue surveillance.

Dr. Wallis: Dr. Porten, do you follow a similar approach?

Dr. Porten: Yes, my approach aligns with Dr. Agarwal’s. Conducting periodic biopsies in the office is also an option for reassurance.

Dr. Daneshmand: While I share the practice of obtaining cells directly from the tumor site, I express concerns about cytology sensitivity. The Flex Blue Light study demonstrated challenges in detecting high-grade disease solely through cytology. This raises the question of whether negative cytology implies less aggressive biology. Regardless, incorporating biopsies remains a standard practice.

Dr. Agarwal: Biopsies are indeed straightforward.

Dr. Wallis: Dr. Porten, you mentioned the need for longer-term follow-up on recent trials. What other information should we gather as a community, and what studies are necessary to potentially alter our treatment approach for intermediate-risk cases?

Dr. Porten: Mechanism of action and sequential assessments, similar to medical oncology practices, are essential. Exploring urinary biomarkers is particularly promising in the non-muscle invasive disease space. These biomarkers could aid in diagnosis and monitoring, offering valuable insights.

Dr. Wallis: Dr. Agarwal, you mentioned the evolving field of diagnostics. Are these innovations more focused on initial diagnosis or ongoing monitoring?

Dr. Agarwal: The field is rapidly evolving. Circulating tumor DNA, extracted reliably from urine, shows promise. We might define intermediate-risk based on molecular profiles obtained from urine tumors, allowing for more personalized treatment approaches. This could involve specific therapies tailored to each patient’s molecular profile.

Dr. Daneshmand: Newer biomarkers, quantifying tumor amounts in the bladder, offer opportunities to monitor treatment responses. The future may involve predicting responses based on quantifiable markers like tumor DNA or methylation markers.

Dr. Wallis: Dr. Daneshmand, you alluded to actionable mutations. What are your thoughts on FGFR targeting in this space?

Dr. Daneshmand: FGFR targeting is a hot topic, spanning low-grade to metastatic disease. Interestingly, low-grade tumors exhibit higher FGFR3 alterations than metastatic ones. While upper tract and lower tract carcinomas share FGFR3 alterations, the upper tract sees them more commonly. Trials like PROOF 302 revealed challenges, but ongoing efforts explore FGFR targeting’s potential, even in non-muscle invasive disease.

Dr. Wallis: As we conclude, each of you, in the next 12 months, what are you most looking forward to in the non-muscle-based bladder cancer field?

Dr. Daneshmand: I’m eager to see Dr. Porten’s biomarker urine response data and anticipate the 6 to 12-month trial results. FDA approvals are particularly exciting, providing more treatment options and avenues for research.

Dr. Agarwal: I echo the excitement for FDA approvals and the evolving landscape of bladder cancer treatment. Additionally, I’m intrigued by the resurgence of photodynamic therapy, showing promise in novel trials.

Dr. Porten: The CISTO study’s results on patient and caregiver perspectives, along with clinical outcomes, are expected in the next year. This could inform decision-making and improve the quality of life for patients. It’s an exciting time as we explore numerous therapeutic possibilities in the coming years.

Dr. Wallis: I sincerely appreciate your time, and this conversation has been truly enriching. Learning from your insights and expertise has been a valuable experience. I trust it has been both interesting and informative for you as well. As a field, we have much to anticipate, and I am optimistic that, in the next 6 to 12 months, we will witness an expansion of options for our patients dealing with non-muscle invasive bladder cancer.