In a phase II trial (RETAIN 1) reported in the Journal of Clinical Oncology, Geynisman et al found that risk-adapted active surveillance following neoadjuvant chemotherapy was associated with a high rate of metastasis-free survival in patients with muscle-invasive bladder cancer.
Study Details
In the U.S. multicenter trial, 70 patients with cT2–T3N0M0 disease enrolled between October 2017 and May 2020 received neoadjuvant chemotherapy with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC). Transurethral bladder tumor specimens obtained prior to neoadjuvant chemotherapy were assessed for mutations in ATM, ERCC2, FANCC, and RB1; patients with at least one mutation and cT0 after neoadjuvant chemotherapy began active surveillance. Other patients received intravesical therapy, chemoradiotherapy, or cystectomy after neoadjuvant chemotherapy. The primary outcome measure was metastasis-free survival at 2 years in the total population; the null hypothesis was rejected if the lower-bound exact one-sided 95% confidence interval (CI) exceeded 64%.
Key Findings
Among the 70 patients, 33 (47%) had a predefined mutation, and 25 (36%) began per-protocol active surveillance.
With a median follow-up of 40 months, the 2-year metastasis-free survival among all patients was 72.9% (lower-bound exact one-sided 95% CI = 62.8%; thus, not rejecting the null hypothesis). Metastasis-free survival at 2 years was 76.0% (95% CI = 54.2%–88.4%) in the active surveillance group and 71.1% (95% CI = 55.5%–82.1%) in the non–active surveillance group. In the active surveillance group, 17 patients (68%) had some recurrence, and 12 patients (48%) were metastasis-free with an intact bladder.
Overall survival at 2 years was 84.3% (95% CI = 73.4%–91.0%) among all patients, 88.0% (95% CI = 67.3%–96.0%) in the active surveillance group, and 82.2% (95% CI = 67.6%–90.7%) in the non–active surveillance group.
The investigators concluded: “Patients with [muscle-invasive bladder cancer] treated with AMVAC followed by a risk-adapted approach to local consolidation achieved a 2-year [metastasis-free survival] rate of 73%. The primary endpoint was not met, but 17% of all enrolled patients and 48% of the active surveillance group avoided cystectomy without metastatic disease.”
Daniel M. Geynisman, MD, of Fox Chase Cancer Center, Philadelphia, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by a grant from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
