(UroToday.com) Dr. Gore kicked off this session with a talk on Innovative and Pragmatic Methods to Study BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC).
First, he started talking about the “Why” we need a pragmatic approach. First and foremost, because the patient’s asked for it! In a survey of 591 patients (through BCAN Patient Survey Network), of the top concerns for patients, “How can patients and providers make decisions about the need for cystectomy and what is the best timing?” and “what are the best treatments for patients whose cancer returns or worsen after BCG treatment” topped the list.
But, it is also important to clinicians – anecdotally (through discussions with clinician advisors) and by the very fact that there is so much variability in practice, there remains significant uncertainty in the management of patients with non muscle invasive bladder cancer.
Next, looking at the “Who” for the pragmatic approach, he presented the most recent update to the BCG treatment response terminology.
But, he notes that beyond BCG therapy, there are also many patients in our practices that are recurrent despite salvage therapies (such as intravesical gem/doce). He also pointed out, that in the BCG shortage, many patients are also not able to get enough BCG to meet some of the above criteria, even for trial enrollment.
More broadly, these are approaches of how to manage recurrent high-grade NMIBC rather than just BCG refractory NMIBC.
Next is the “What” – what are we measuring? What are the outcomes of importance? Our frame of reference is almost always clinical outcomes such as recurrence-free survival, CR rates at 12 months, progression to MIBC, etc. However, going back to the patient survey through BCAN, there may be other important outcomes we aren’t considering: generic quality of life, urinary quality of life, bladder preservation, caregiver burden and financial burden. These are very important to patients – and should be important to us.
He reminded us that patient reported outcomes are critical, as PRO’s can vary significantly with physician perception on patient outcomes.
Lastly, he asked the question of what should the comparator be? Most trials in BCG unresponsive NMIBC are single arm trials. But, the paradigm for salvage therapies has drastically changed. In the past few years, salvage intravesical gem/doce has become predominant replacing repeat BCG, but other therapies (pembrolizumab, etc), have become utilized. From the CISTO study, which he talks about later, he notes the changing trends in the salvage therapy of HG recurrent NMIBC:
Finally, is the “How” do we do these trials – what is the intersection between patient preferences and trial design? When patients were asked if they would be willing to be randomized to cystectomy vs. additional treatments delivered to the bladder, 90% would have declined trial enrollment. This highlights the difficulty of a randomized trial in this space with cystectomy as the gold standard. This is supported by the fact that many prior surgical trials in the GU space where a non-surgical option was the alternative had very poor accruals (CARMENA, SURTIME, PIVOT, START, SPIRIT).
Comparing pragmatic vs. explanatory trials, pragmatic trials explore external validity and need larger sample sizes and diverse settings.
He then talked about the CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer), which he leads with Dr. Angie Smith. The trial design is below:
This is an observational study of 36 centers of patients who self-select cystectomy and bladder-sparing options. But the outcomes include patient specific outcomes and oncologic outcomes. Importantly, the 36 sites includes sites from around the country, but also include academic and non-academic clinical practices.
His conclusion slide highlighted the importance of using a patient-centered design focusing on patient-centered outcomes to generate generalizable results.
Presented by: John L. Gore, MD, Department of Urology, University of Washington
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.