(UroToday.com) The 2025 AUA annual meeting featured a bladder cancer clinical trials in progress session and a presentation by Dr. Marie-Pier St-Laurent discussing NEO-BLAST, a trial assessing neoadjuvant therapy for bladder cancer followed by active surveillance versus treatment. Approximately 30-40% of patients have a pathologic complete response after neoadjuvant therapy, suggesting that these patients could potentially avoid definitive bladder treatment. Multiple retrospective studies of patients with complete response following neoadjuvant chemotherapy who decline radical cystectomy suggest that surveillance may be safe, with 5-year overall survival rates of approximately 85%. However, recent phase 2 trials have shown mixed results for surveillance, with 2 year metastasis free survival rates of 76% to 96%. The current clinical tools used to detect residual disease prior to cystectomy are inadequate, but novel adjuncts, such as circulating tumor DNA, may improve our ability to determine complete response. The question remains whether patients with complete response require definitive bladder treatment or if surveillance is a safe alternative. Can the combined use of all modalities (cytology, CT, cystoscopy/TURBT, ctDNA, urinary tumor DNA, MRI) enhance accuracy of clinical re-staging after neoadjuvant systemic therapy and make bladder preservation safer?
In NEO-BLAST, patients will have standard of care neoadjuvant therapy for cT2-4aN0M0 bladder cancer, followed by restaging with ctDNA, MRI of the pelvis, TURBT + cytology, and CT chest/abdomen/pelvis. Those that are deemed >= T1 will have radical cystectomy or trimodality therapy followed by surveillance. Those that are deemed to have a clinical complete response will be randomized to definitive local treatment versus active surveillance. The definition of clinical complete response for this trial is:
- Negative MRI (VI-RADS 0-2)
- Negative repeat TURBT (<cT1, no extensive CIS)
- Negative ctDNA
- No metastasis (negative conventional CT/MRI or PET/CT)
The trial design for NEO-BLAST is as follows:
There will be a phase 2 lead in portion of this trial that will assess the feasibility of randomizing muscle invasive bladder cancer patients with clinical complete response to active surveillance versus definitive bladder treatment. For the phase 3 portion, the primary outcome will be 2-year metastasis free survival for patients with clinical complete response managed with active surveillance versus definitive bladder treatment. Secondary outcomes will be bladder intact event free survival, overall survival, treatment acceptance rates, and quality of life.
For the statistical plan, in the phase 2 portion, the trialists will approach 240 patients over 2 years, anticipating that 30% will enroll (n = 72) and >25% (>18 patients) will have a complete clinical response and allow randomization. In the phase 3 portion, this will be a non-inferior design with a 10% non-inferior margin. Assuming a 5% event rate at 2 years in both groups and a type I error of 5% (1-sided), this will yield 78 patients per group to provide 80% power to reject the hypothesis of inferiority. Assuming a 10% loss to follow-up, 172 patients will be randomized (688 enrolled and restaged, if assuming a conservative clinical complete response rate of 35%).
Dr. St-Laurent concluded her presentation discussing NEO-BLAST with the following take home points:
- More effective neoadjuvant therapies will push us more to consider bladder preservation
- Complete clinical response to neoadjuvant therapy requires better determination (combination of MRI, ctDNA), and we need to determine if the bladder requires definitive treatment, or whether active surveillance is safe
- Neo-BLAST will answer these questions, with a planned multi-site launch in British Columbia in July 2025
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 American Urological Association (AUA) annual meeting held in Las Vegas, NV, Saturday, April 26 - Tuesday, April 29, 2025