Fox Chase-developed RETAIN clinical trials explore bladder preservation for selected patients

“At the end of the day, nothing is better than a patient’s own bladder,” said Alexander Kutikov, MD, FACS, Co-Executive Director of the Fox Chase – Temple Urologic Institute and Chair of Urology at Fox Chase. For decades, the standard treatment for muscle-invasive bladder cancer has been pre-operative chemotherapy followed by cystectomy, or bladder removal—a lifesaving procedure that can permanently change daily life. Some patients require a urostomy bag, while others may receive a new bladder created from small intestine tissue. Either path can save lives, but both can dramatically affect someone’s quality of life.

Early work led by Elizabeth Plimack, MD, MS, FASCO, Deputy Director of Fox Chase Cancer Center and Professor of Hematology/Oncology, helped change that scenario. Her team identified genomic biomarkers that could help select patients for bladder preservation, which, in collaboration with Philip Abbosh, MD, PhD, Assistant Professor in the Nuclear Dynamics and Cancer Program at Fox Chase, helped shape the Fox Chase-directed RETAIN BLADDER trials around a central question: Could selected patients with muscle-invasive bladder cancer receive systemic therapy and avoid immediate bladder removal without compromising cancer control?

Trials Built Around a Patient-Centered Question

“Although each RETAIN-series trial has used slightly different criteria, the studies share a common goal: Identifying patients whose clinical and biological features suggest they may respond well enough to systemic therapy to consider bladder preservation,” said Kutikov.

The first RETAIN trial, led by Daniel M. Geynisman, MD, Chief of the Division of Genitourinary Medical Oncology, has already published data in the Journal of Clinical Oncology. RETAIN-2 has closed enrollment, but Fox Chase researchers are still following patients long term as the data continue to mature.

The RETAIN approach has evolved over time. Earlier research used tumor biology and treatment response to identify patients who might enter active surveillance instead of immediate bladder removal. RETAIN-2 built on that strategy by pairing chemotherapy with immunotherapy, while newer work is exploring whether circulating tumor DNA, or ctDNA, can help guide bladder-preservation decisions.

Updated data from the phase II RETAIN-2 clinical trial may help guide treatment decisions for patients with muscle-invasive bladder cancer, according to first author Pooja Ghatalia, MD, Associate Professor in the Department of Hematology/Oncology at Fox Chase.

For patients and for urology in general, RETAIN points toward care that is aggressive against cancer, personalized, and more attentive to quality of life.

Still, Kutikov is clear: “Oncologic safety is the top priority here,” he said. “This isn’t about saving someone’s bladder at the expense of cancer control. The goal is to de-escalate treatment without compromising outcomes. Not every patient is a candidate for a bladder-sparing strategy, and careful selection remains essential.”

Bladder Preservation Requires Vigilance

The care team must also be ready to change course quickly. If signs of recurrence or progression emerge, patients may need more definitive treatment, such as surgery or radiation.

The two-year RETAIN data underscored both the promise and the caution built into the strategy. In the active-surveillance group, almost half of patients survived while retaining their bladders. However, metastatic disease still occurred in a substantial minority, reinforcing the need for close surveillance and readiness to change course.

A key finding was that localized recurrence in the bladder could be an important warning sign. When active-surveillance patients developed recurrent localized disease, it often signaled that the team should move toward bladder removal rather than continuing local therapies.

RETAIN Looks Ahead

Fox Chase researchers will continue following patients from the RETAIN-2 trial for five years to study long-term outcomes of bladder-sparing treatment.

“As the next step in refining the Fox Chase bladder-preservation strategy, RETAIN-3 will launch in the fall 2026. The study is a single-arm phase II trial enrolling patients with cT2–T3N0M0 MIBC, with plans to use enfortumab vedotin/pembrolizumab and using ctDNA as an integral biomarker in treatment decision-making,” said Ghatalia. RETAIN-3 will first launch only at Fox Chase, with additional sites added later on.

“The RETAIN approach underscores the benefits of Fox Chase collaboration. Bladder cancer care often requires surgery, drug therapy, radiation, or a combination of those approaches. RETAIN brings together urologic oncology, medical oncology, and radiation oncology around a shared mission of preserving both life and quality of life—an inherent part of Fox Chase culture,” said Kutikov.