The RETAIN trial, a phase II non-inferiority study, investigated a risk-enabled approach to bladder-sparing therapy in patients with muscle-invasive bladder cancer (MIBC) who demonstrated a strong response to neoadjuvant chemotherapy. Although the trial did not meet its primary endpoint, the findings suggest a potential pathway for active surveillance in select patients, offering a chance to avoid radical cystectomy.
The study enrolled patients with T2-T3 MIBC and treated them with three cycles of accelerated MVAC neoadjuvant chemotherapy. Researchers sequenced tissue from the original biopsy, focusing on mutations in ATM, FANCC, ERCC2, and RB1, which are associated with favorable responses to chemotherapy. Patients achieving a complete response on imaging, cystoscopy, and cytology, and harboring one of the specified mutations, were offered active surveillance instead of immediate surgery or chemoradiation. These patients were closely monitored with cystoscopies, imaging, and bloodwork, while those without a complete response or the identified mutations proceeded to standard-of-care treatment, primarily cystectomy.
The primary endpoint was two-year metastasis-free survival for the entire cohort. The trial aimed to demonstrate non-inferiority to the standard of care. Results showed a two-year metastasis-free survival rate of approximately 72%. However, the one-sided 95% confidence interval fell slightly short of the required 64% mark, leading to the conclusion that the trial did not meet its primary endpoint.
Despite not meeting the primary endpoint, the study revealed that roughly 46% of patients undergoing active surveillance were able to maintain their bladder at the two-year mark without developing metastatic disease. Some patients required intravesical therapy, but many successfully avoided bladder removal, representing a significant benefit for this subset.
Further analysis indicated that among the patients on active surveillance who experienced recurrence with metastatic disease (n=10), 80% initially presented with local recurrence, either non-muscle invasive or muscle-invasive. This finding emphasizes the importance of aggressive intervention, potentially including immediate cystectomy, in such cases. The chemotherapy regimen was well-tolerated, and patients generally appreciated the opportunity to avoid cystectomy.
These results, while not definitive, contribute to the growing body of research exploring bladder-sparing strategies. According to the researchers, these results are hypothesis-generating and should be considered alongside other trials in the field to refine patient selection for bladder preservation approaches. Future strategies may incorporate ctDNA analysis, urinary biomarkers, and advanced imaging techniques like MRI to improve patient stratification. Ongoing trials, including one by Alliance and RETAIN-2, are further investigating this approach, building upon the foundation laid by the RETAIN trial.
