Laura Bukavina, MD, MPH, MSc, discusses role for ctDNA following RETAIN data

In an interview at the 2026 ASCO Genitourinary Cancers Symposium in San Francisco, California, Laura Bukavina, MD, MPH, MSc, sat down to discuss the emerging role of circulating tumor DNA (ctDNA) in guiding treatment decisions for patients with muscle-invasive bladder cancer (MIBC), drawing on findings from the RETAIN 1 and RETAIN 2 trials. Bukavina is an assistant professor of urologic oncology at Cleveland Clinic Glickman Urologic Institute, and translational science lead in GU oncology at Cleveland Clinic Lerner College of Medicine in Cleveland, Ohio.

RETAIN 1 evaluated a bladder-preservation strategy following neoadjuvant chemotherapy, while RETAIN 2 incorporated immunotherapy with nivolumab (Opdivo). In both studies, patients with specific tumor mutations who achieved no visible residual disease on imaging and cystoscopy could enter a surveillance strategy rather than proceed directly to cystectomy. RETAIN 2 demonstrated somewhat higher pathologic complete response rates compared with RETAIN 1, likely reflecting the addition of immunotherapy.

A key focus of the analysis presented by Pooja Ghatalia, MD, was the ability of ctDNA to help determine which patients with a clinical complete response (cCR) truly achieved a pathologic complete response (pCR). Investigators evaluated ctDNA longitudinally throughout treatment and surveillance to assess its predictive value within the bladder-preservation paradigm. According to Bukavina, the data suggest that ctDNA alone does not reliably predict residual bladder disease or local recurrence. Patients with T2 or higher tumors can still have negative ctDNA results, highlighting limitations in its sensitivity for detecting residual bladder tumors.

However, ctDNA was prognostic for systemic disease control, with ctDNA positivity associated with a 10.7x higher risk of inferior metastasis-free survival (P < .0001) and poor outcomes despite cystectomy. She noted that future strategies may require a multimodal approach that integrates ctDNA with additional biomarkers and improved imaging techniques, such as urine tumor DNA testing and dedicated MRI protocols, to better identify patients who can safely avoid cystectomy. Several ongoing clinical trials are currently evaluating these combined strategies.

REFERENCE

1. Ghatalia P, Ross EA, Zibelman MR, et al. Circulating tumor DNA (ctDNA) to guide response-adapted bladder preservation in muscle invasive bladder cancer (MIBC): Integrated analysis of the RETAIN trials. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA632. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16924