Circulating tumor DNA (ctDNA) may be used to predict metastatic risk and identify which patients with muscle-invasive bladder cancer are more likely to benefit from a bladder-sparing treatment approach, according to findings from the RETAIN trials presented at the 2026 ASCO Genitourinary Cancers Symposium (Abstract LBA632).
In RETAIN-2, post-treatment ctDNA negativity led to the ability to accurately predict metastatic control, but not local-only recurrences in patients on active surveillance.
“This tells us ctDNA can be incorporated into the decision-making of who should keep their bladder and who should not, knowing that we also need additional tests or biomarkers to detect local recurrence early in patients who undergo active surveillance,” stated first author Pooja Ghatalia, MD, Associate Professor in the Department of Hematology/Oncology at Fox Chase Cancer Center.
Background and Study Methods
The phase II RETAIN 1 and 2 trials explored a response-adapted approach to determining which patients with muscle-invasive bladder cancer can safely undergo cystectomy-sparing active surveillance following neoadjuvant therapy.
In the RETAIN-1 trial, patients received AMVAC (accelerated methotrexate, vinblastine, doxorubicin, and cisplatin), and in RETAIN-2, they received nivolumab plus AMVAC. Patients enrolled in RETAIN-2 had cT2-T3N0M0 muscle-invasive bladder cancer and had undergone a transurethral resection of bladder tumor (TURBT). Samples from the procedure were sequenced for mutations, and patients with at least one mutation and a clinical complete response were assigned to receive active surveillance; all others received bladder-directed therapy.
The primary endpoint of the RETAIN-2 trial was the 2-year metastasis-free survival rate.
Key Findings
A total of 71 patients were evaluable for response in the RETAIN-2 trial, and 57 of these patients (80.3%) were metastasis-free at 29.2 months. The 2-year metastasis-free survival rate was 79.8% (95% confidence interval [CI] = 70%–90%) in the intent-to-treat population and 80% (95% CI = 64%–100%) in patients undergoing active surveillance.
In 22 patients receiving active surveillance, 36% had bladder recurrence, 18% developed metastases, 18% needed salvage cystectomy, and 14% needed salvage chemoradiation. Seventy-three percent of these patients were metastasis-free and had an intact bladder. Only three of these patients were ctDNA-positive.
In both RETAIN-1 and RETAIN-2, among 111 patients, 274 ctDNA draws were collected, showing baseline ctDNA positivity in 42.2% and post-treatment positivity in 13.6%. Of the patients who were positive at baseline, 72.7% cleared ctDNA.
Those who were ctDNA-negative after treatment or who cleared their ctDNA from being positive at baseline had a lower recurrence risk. Recurrence rates were 34.8% for patients who were ctDNA-negative, 43.8% for patients who cleared their ctDNA, 85.7% for patients with ctDNA positivity at baseline, and 91.7% in patients who did not clear their ctDNA after treatment.
In patients on active surveillance who were ctDNA-negative after treatment, their 1-year metastasis-free survival rate was 97.1%, and their 2-year metastasis-free survival rate was 82.4%.
The recurrence-free survival rate at 1 year was 62.9% and was 50.7% at 2 years, mostly due to local recurrences. “This limitation may reflect the field effect characteristic of bladder cancer, or simply the poor sensitivity of plasma ctDNA for detecting [measurable] residual disease confined to the bladder,” the study authors commented in their abstract.
The RETAIN-3 trial is currently being designed to explore the use of ctDNA as a predictive biomarker for treatment decision-making in patients with bladder cancer.
DISCLOSURE: For full disclosures of the study authors, visit meetings.asco.org.
