Feb. 19, 2026
For patients with metastatic urothelial carcinoma, even the most favorable outcomes from cisplatin-based combination therapy — the current standard of care for advanced bladder cancer — result in a median survival of only 14 to 15 months. Outcomes are even worse for patients who are not eligible for these therapies, including those with poor kidney function.
However, a new therapy of enfortumab vedotin and pembrolizumab is offering new hope for patients. This combination chemotherapy treatment, which received Food and Drug Administration approval in 2024 after clinical trials, nearly doubled survival rates to 30 months compared with the current standard.
As a follow-on to these successful trials, Parminder Singh, M.D., a hematologist at Mayo Clinic in Arizona, led a study to evaluate the real-world outcomes for patients using this combination treatment. This study included both patients who received the therapy as a first line treatment as well as those who had this therapy as a second line treatment after cisplatin. The outcomes from this study mirrored those of the clinical trial for both groups, with a 25-month median survival as a first line treatment and 26 months as a second line treatment.
"Even as a second line treatment for patients who have had chemotherapy before, the outcome was still as good as when given as a first line treatment," says Dr. Singh. "That highlights that this combination is effective in the real world: No matter where it's given in the patient journey, it's improving outcomes."
Tailoring the treatment approach after clinical trials
Because this study was not limited by the protocols of the clinical trial, Dr. Singh and his team were able to tailor treatment to the patients in their care. For example, the care team was able to offer this treatment to patients with kidney failure, who had been excluded from the clinical trial. The researchers found that these patients could tolerate the treatment and identified ways to adjust the schedule to limit toxicity, especially for patients on dialysis.
"Instead of giving treatments on days 1 and 8 of the schedule, we'd treat on days 1 and 15 and repeat every 28 days," says Dr. Singh. "We adjusted this schedule for 12 patients and demonstrated that we could safely give this combination without extra toxicities. It's a small number, but it gives confidence that these side effects are manageable and offers avenues for future studies."
The researchers also found that patients with a complete response could go on a treatment break. For those patients whose cancer came back, Dr. Singh's team restarted therapy and was able to control the disease from growing further.
"We might be concerned that if cancer progresses after treatment, patients might not respond to that treatment again," Dr. Singh says. "While this concept still needs to be validated, we saw in our study that this treatment is so effective that we don't need to complete the course. We can restart the therapy if needed and still get a response later. That means we can tailor treatment based on what they need and possibly offer a treatment break."
One outcome of this study was finding ways to bring this treatment to the broader medical community, including how to keep oncologists informed on what to expect during treatment. For example, this treatment is a novel combination, which means there are side effects not seen with conventional bladder cancer treatment. These include rash, neuropathy and rising blood sugar.
"These side effects are manageable, but we encourage community physicians to be proactive with managing them," says Dr. Singh. "Being proactive and managing these side effects upfront helped us continue treatment longer and achieve durable remission."
Improving outcomes for all patients with bladder cancer
This combination treatment is changing the approach to treating bladder cancer and was recently approved to treat nonmetastatic cancer at earlier stages.
"If these patients get this combination treatment earlier, maybe they don't reach stage 4," says Dr. Singh. "We may see fewer patients who need treatment for advanced disease, or we may see patients who need newer combinations of therapies. These are the new challenges for our next steps of research."
Mayo Clinic is continuing studies to improve outcomes for patients with bladder cancer. For example, Dr. Singh is conducting research on tests that can be used to understand which patients are responding well to treatment. He also is collaborating with radiation oncologists at Mayo Clinic on better imaging protocols to be more accurate in clinical staging of bladder cancer, which improves the likelihood that patients receive appropriate treatment.
"At Mayo Clinic, we are at the forefront of bladder cancer research at every stage," says Dr. Singh. "We lead numerous clinical trials at the national and international levels, bringing state-of-the-art medications for patients at our clinic. Our nationally recognized multidisciplinary care team includes radiation oncologists, surgical oncologists and medical oncologists who work together to improve patient outcomes in bladder cancer."
For more information
Jain P, et al. Real-world outcomes of enfortumab vedotin and pembrolizumab in advanced urothelial carcinoma: A multicenter retrospective analysis. Clinical Genitourinary Cancer. 2025;23:102453.
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