A phase II trial, RETAIN 1, explored a risk-adapted approach to treating muscle-invasive bladder cancer (MIBC) following neoadjuvant chemotherapy (NAC). The study, published in the Journal of Clinical Oncology, investigated whether biomarker selection and clinical staging could identify patients suitable for active surveillance (AS) as an alternative to cystectomy.
The trial enrolled 70 patients with cT2-T3N0M0 MIBC who underwent NAC with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC). Pre-NAC tumor samples were sequenced for mutations in ATM, ERCC2, FANCC, and RB1. Patients with at least one mutation and cT0 status post-NAC began AS.
Key Findings from the RETAIN 1 Trial
With a median follow-up of 40 months, the 2-year metastasis-free survival (MFS) for all patients was 72.9% (lower bound exact one-sided 95% CI, 62.8). In the AS group, the 2-year MFS was 76.0% (95% CI, 54.2 to 88.4), while it was 71.1% (95% CI, 55.5 to 82.1) in the remaining patients. Notably, 17% of all enrolled patients and 48% of the AS group avoided cystectomy without metastatic disease.
Overall survival (OS) at 2 years was 84.3% (95% CI, 73.4 to 91.0). The OS was 88.0% (95% CI, 67.3 to 96.0) in the AS group and 82.2% (95% CI, 67.6 to 90.7) in the non-AS groups, respectively.
Active Surveillance Outcomes
In the AS group, 17 patients (68%) experienced some recurrence, and 12 (48%) remained metastasis-free with an intact bladder. Eight patients (32%) in the AS group remained disease-free. Recurrences were managed with intravesical therapy (4 patients), radiation (2 patients), cystectomy (8 patients), and/or systemic therapy (7 patients).
Safety and Tolerability
Fourteen out of 78 patients experienced grade 3 to 5 treatment-related adverse events (TRAEs). Four patients discontinued AMVAC after one cycle due to acute kidney injury, and one death occurred due to sepsis after three cycles of AMVAC.
Clinical Implications
The study suggests that a risk-adapted approach using AMVAC followed by local consolidation can achieve a 2-year MFS rate of 73% in patients with MIBC. While the primary endpoint was not met, the results indicate that a meaningful subset of patients can avoid cystectomy without metastatic disease. "The benefit to the patients in our study was a 53% cystectomy rate in the ITT, allowing a meaningful subset of patients to avoid life-altering surgery in situations where it may have been safely avoided," the study authors noted.
Nivolumab as Adjuvant Therapy
Separately, data from the phase 3 CheckMate-274 trial presented at the 2025 ASCO Genitourinary Cancers Symposium showed a sustained improvement in disease-free survival (DFS) among patients with MIBC who received adjuvant nivolumab versus placebo. In all randomized patients with MIBC, the median DFS was 25.6 months with nivolumab vs 8.5 months with placebo (HR, 0.63; 95% CI, 0.51-0.78).
Matthew I. Milowsky, MD, FASCO, stated, "The improvements demonstrated in patients with MIBC provide additional support for adjuvant nivolumab as a standard of care for high-risk muscle-invasive urothelial carcinoma, including MIBC after radical surgery, and regardless of prior neoadjuvant chemotherapy."
