Expert Insight

  • In conversations with two leading voices in bladder cancer care — Dr. Leilei Xia of Penn Medicine and Dr. Gary Steinberg of Rush University Medical Center — there is clear agreement: the combination of enfortumab vedotin plus pembrolizumab represents one of the most consequential advances in muscle-invasive bladder cancer in years.
  • As data mature across metastatic and perioperative settings, both physicians see the regimen not simply as an incremental improvement, but as a therapy poised to redefine the standard of care.

In the bladder cancer care community, doctors are increasingly in agreement that enfortumab vedotin plus pembrolizumab will play a bigger role across more settings.

An Assistant Professor of Surgery at the Hospital of the University of Pennsylvania and expert in the care of bladder cancer patients, Dr. Leilei Xia views perioperative EV plus pembrolizumab as a pivotal advance in muscle-invasive bladder cancer (MIBC), citing emerging data suggesting deeper responses than traditional neoadjuvant chemotherapy and expanding options for cisplatin-ineligible patients.

“The standard of care used to be chemotherapy followed by radical cystectomy,” Dr. Xia says. “Nowadays for renal toxic–ineligible patients, we have a good option… It is likely that this becomes a new standard of care for all muscle-invasive bladder cancer patients before cystectomy, in my opinion, because the effectiveness seems better than traditional neoadjuvant chemotherapy.”

One of Dr. Xia’s peers, Dr. Gary Steinberg, Professor of Urology at Rush University Medical Center and former Director of the Bladder Cancer program at NYU Langone, concurs, calling this powerful cancer fighting combination the “first and foremost”advance in bladder cancer care to take place in the last couple years.

Historically, cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy defined standard treatment. But for patients ineligible for cisplatin — particularly those with renal impairment — therapeutic options have been limited.

The combination — enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, plus the PD-1 inhibitor pembrolizumab — is already established in metastatic disease. Its expansion into the perioperative setting signals what Dr. Xia sees as a broader paradigm shift in systemic therapy for bladder cancer.

Dr. Steinberg notes, “When we combine [EV plus pembrolizumab], the antibody drug conjugate and the checkpoint inhibitor in bladder cancer, we’re seeing just really profound responses in the metastatic setting. We’ve gone from a complete response rate in a durable response rate of about 15 months with the addition of PAD sev and Keytruda that’s now going to 36 months. So we’ve almost tripled at least more than doubled, but close to tripled the durability and the response rate.

Importantly, emerging data demonstrating high pathologic complete response rates are fueling broader conversations about bladder preservation. Dr. Steinberg adds, “[with] the neoadjuvant or upfront addition of EV and pembrolizumab, we’re seeing really profound complete response rates. These patients are also getting adjuvant therapy as well, but we’re seeing really profound complete response rates leading to the strong push for bladder preservation with patients with muscle-invasive disease.”

For Dr. Xia, these response rates underscore a shift that extends beyond simply offering an alternative for cisplatin-ineligible patients. They represent a potential redefinition of the neoadjuvant backbone in MIBC — one that may ultimately challenge long-standing chemotherapy standards and reshape the role of surgery in select patients.

“The standard of care is EV and pembrolizumab for metastatic bladder cancer already,” Dr. Xia says, predicting that it will move to become the standard of care in more settings.

As systemic therapy moves earlier in the disease course, perioperative EV plus pembrolizumab is not merely expanding options — it is recalibrating expectations.