Pooja Ghatalia, MD shares new insights from RETAIN trials in MIBC

At the 2026 ASCO Genitourinary (GU) Cancers Symposium in San Francisco, California, Pooja Ghatalia, MD, discussed previous and updated data from the RETAIN trials in muscle-invasive bladder cancer (MIBC).¹ Ghatalia is a medical oncologist at Fox Chase Cancer Center in Philadelphia, Pennsylvania.

Ghatalia explained that although the standard of care for MIBC remains neoadjuvant chemotherapy followed by radical cystectomy or chemoradiation, cystectomy carries substantial morbidity and long-term quality-of-life implications. Given that 35% to 60% of patients achieve a complete response to neoadjuvant therapy, there has been ongoing interest in identifying patients who may safely avoid cystectomy. However, conventional restaging methods such as cystoscopy with biopsy, imaging, and urine cytology can miss residual muscle-invasive disease in a significant proportion of patients. To address this gap, RETAIN-1 and RETAIN-2 incorporated tumor mutational biomarkers associated with cisplatin sensitivity to help guide post-neoadjuvant management. RETAIN-1 evaluated neoadjuvant dose-dense MVAC, while RETAIN-2 added nivolumab to chemotherapy. Patients with predictive mutations and a clinical complete response were offered active surveillance, whereas others were advised to pursue definitive local therapy.

Ghatalia reported that RETAIN-2 met its primary end point, with improved outcomes compared with RETAIN-1, potentially reflecting the addition of nivolumab. Patients managed with active surveillance in RETAIN-2 experienced fewer local recurrences and fewer metastatic events than those in RETAIN-1.

The integrated circulating tumor DNA (ctDNA) analysis, which included patients from both trials, demonstrated that ctDNA is a powerful prognostic biomarker. Baseline and post–neoadjuvant therapy ctDNA positivity was associated with significantly worse metastasis-free and overall survival. Patients who remained ctDNA-negative before and after treatment and those who cleared ctDNA demonstrated lower recurrence risks compared with those with persistent ctDNA positivity or non-clearers (34.8% and 43.8% for negative/clearance vs 85.7% and 91.7% for positivity/non-clearance; P < .001 and P < .01, respectively). In RETAIN-2, additional 3- and 6-month ctDNA time points reinforced that ctDNA positivity at any time was associated with inferior systemic outcomes.

Importantly, exploratory analyses suggested that ctDNA status may help inform treatment decisions between active surveillance and cystectomy. Patients who were ctDNA-positive had poor outcomes regardless of whether they underwent cystectomy, while ctDNA-negative patients had similar metastasis-free survival whether they received cystectomy or active surveillance, raising the provocative possibility that ctDNA could help guide bladder-sparing strategies. However, Ghatalia emphasized that ctDNA appears far better at predicting systemic recurrence than local bladder control. CtDNA demonstrated a high positive predictive value for residual disease but a low negative predictive value for pathologic complete response, and many patients with local recurrence were ctDNA-negative. Thus, while ctDNA shows strong promise as a prognostic marker for systemic disease, Ghatalia noted that it cannot reliably rule out residual or recurrent intravesical disease, underscoring the continued need for careful local surveillance strategies.

REFERENCE

1. Ghatalia P. 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://www.asco.org/abstracts-presentations/256835