Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1)

Area of Science:

• Oncology
• Genitourinary Cancer Research
• Clinical Trial Analysis

Background:

• Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is standard for muscle-invasive bladder cancer (MIBC).
• DNA damage repair gene mutations correlate with better response to NAC.
• Identifying candidates for less invasive treatments like active surveillance (AS) is crucial.

Purpose of the Study:

• To evaluate a risk-adapted strategy combining biomarker selection and clinical staging for MIBC patients.
• To identify patients suitable for cystectomy-sparing active surveillance (AS) after NAC.
• To assess metastasis-free survival (MFS) in a phase II noninferiority trial.

Main Methods:

• A single-arm, phase II trial enrolled patients with cT2-T3N0M0 MIBC.
• Patients received NAC with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC).
• Pre-NAC tumor specimens were sequenced for mutations in ATM, ERCC2, FANCC, and RB1. Patients with mutations and cT0 post-NAC proceeded to AS.

Main Results:

• 33% of 70 enrolled patients had relevant mutations; 36% initiated AS.
• The 2-year metastasis-free survival (MFS) for the entire cohort was 72.9%.
• In the AS group, 48% remained metastasis-free with an intact bladder; 17% of all patients avoided cystectomy without metastasis.

Conclusions:

• The risk-adapted approach using AMVAC chemotherapy and biomarker selection achieved a 73% 2-year MFS rate in MIBC patients.
• While the primary endpoint was not met, a significant proportion of patients avoided cystectomy.
• This strategy shows potential for selecting MIBC patients for active surveillance, preserving the bladder without increasing metastatic risk.