Bladder Preservation in MIBC: Promise and Caution in Neoadjuvant Therapy

Enrique Grande, the program director of One Oncology Madrid at Quironsalud, stood at the center of a debate that matters to thousands of bladder cancer patients each year: whether doctors can safely skip the removal of the bladder itself in cases of muscle-invasive disease.

The question arose from promising numbers. When patients received perioperative chemotherapy—specifically the combination of ensitrelvimab and pembrolizumab—alongside standard treatment, pathologic complete response rates climbed to between 55 and 57 percent. Those are substantial figures. They suggest that in more than half of cases, chemotherapy can eliminate all detectable cancer from the bladder tissue examined after surgery. For patients facing the prospect of permanent urinary diversion, the possibility of keeping their bladder intact carries obvious weight.

But Grande's caution, shared during remarks at the American Urological Association's 2026 plenary session, cut to the heart of a clinical trap: the appearance of success and actual success are not the same thing. When doctors perform an endoscopic examination of the bladder—looking directly inside with a camera to assess whether visible tumor has disappeared—they call a negative result a clinical complete response. It sounds definitive. Yet Grande and his colleagues, including Ashish Kamat, Amy Luckenbaugh, and Alejandro Rodriguez, found something troubling in the data. Fifty-two percent of patients who showed a clinical complete response on endoscopy still harbored residual tumor when the bladder was ultimately removed and examined under a microscope. More than half. That means the eye—even the trained eye—was missing cancer that remained.

The problem extends beyond what endoscopy can see. Circulating tumor DNA, or ctDNA, has emerged as a promising tool for detecting residual disease without surgery. Cancer cells shed fragments of their genetic material into the bloodstream, and modern testing can pick up these traces. But ctDNA is not infallible. The testing misses up to one in five cases of residual disease—meaning a patient could receive a reassuring negative result and still harbor undetected cancer.

These gaps matter because bladder preservation strategies hinge on confidence. If a patient is deemed to have achieved complete response and the cancer is truly gone, deferring cystectomy—the surgical removal of the bladder—makes sense. The patient avoids a major operation, maintains normal urinary function, and preserves quality of life. But if residual disease is present and missed, the cancer has time to progress while the patient waits for follow-up imaging or surveillance. The stakes are survival.

Grande's position was not that bladder preservation is impossible. Rather, he argued that it is achievable in carefully selected patients—those who meet strict criteria and whose response to treatment can be verified with high confidence. But that verification does not yet exist in reliable form. Clinical complete response on endoscopy is not enough. ctDNA testing, while useful, has blind spots. The field needs prospective, rigorous validation studies before oncologists and urologists can confidently recommend deferring cystectomy as standard practice.

The debate reflects a broader tension in cancer care: the desire to minimize harm and preserve function must be balanced against the imperative to eliminate disease. The chemotherapy regimens are real. The response rates are real. But the gap between what appears to be gone and what is actually gone remains wide enough that caution, for now, is warranted.