RETAIN-2 Results: ctDNA-Guided Bladder Preservation in MIBC

Dr. Pooja Ghatalia presents findings from RETAIN-2, a single-arm phase 2 non-randomized trial evaluating a bladder-preservation strategy in patients with clinical T2–T3 N0 muscle-invasive bladder cancer (MIBC). The abstract also incorporates a combined ctDNA analysis drawn from both RETAIN-1 and RETAIN-2.

In RETAIN-2, patients received neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (MVAC) plus nivolumab (Opdivo) for 3 cycles. Concurrently, pretreatment tissue was analyzed for mutations in ATM, ERCC2, and RB1, which are biomarkers previously associated with cisplatin response. Following neoadjuvant therapy, patients underwent clinical restaging, including endoscopic bladder assessment, 4 random biopsies to rule out hidden disease, urine cytology, and CT imaging.

Patients who showed no residual disease and carried 1 of the favorable mutations proceeded to active surveillance, consisting of cystoscopy every 3 months alongside CT imaging. Those with residual disease or without a favorable mutation went on to local intervention such as cystectomy or chemoradiation, though 3 patients received intravesical therapy.
The primary end point was 2-year metastasis-free survival (MFS) in the intention-to-treat population, using a non-inferiority design with a historical control threshold of 56%. At a median follow-up of 32.3 months, approximately 70% of patients were metastasis-free at 2 years, with the lower bound of the 90% confidence interval at 62.4%, which exceeds the non-inferiority threshold and confirming the primary end point was met.

Among the 22 active surveillance patients, 68% remained metastasis-free with an intact, non-irradiated bladder. This compares favorably to RETAIN-1, where the equivalent figure was 48%, a difference Dr Ghatalia attributes to the incorporation of immunotherapy in RETAIN-2.