Mega Doctor News
By Brittany Cordeiro/ Mayo Clinic News Network
Cancers of the reproductive and urinary organs, known as genitourinary cancers, affect millions of people worldwide each year. At Mayo Clinic, Yousef Zakharia, M.D., a medical oncologist and chair of the Genitourinary Disease Group at the Mayo Clinic Comprehensive Cancer Center, leads clinical research aimed at improving outcomes for patients with kidney, bladder and prostate cancers.
In addition to overseeing the disease group, he serves as leader of the Experimental Therapeutics Program at Mayo Clinic in Arizona, where he develops and evaluates new treatments for patients whose cancer has progressed after standard therapies.
“We’ve made significant progress in cancer therapies,” Dr. Zakharia says. “But there is still more work to do, especially for patients whose disease no longer responds to standard therapies. Clinical trials help us expand options and move the field forward.”
Expanding treatment options in bladder cancer
For many years, cisplatin-based chemotherapy was the primary treatment for bladder cancer. Researchers have recently identified newer treatment options that improve outcomes and are generally well tolerated, including enfortumab vedotin, an antibody-drug conjugate, and the immunotherapy drug pembrolizumab.
Initially approved by the Food and Drug Administration for advanced disease, the combination is now being evaluated before surgery in patients with localized cancer, meaning the cancer has not spread to distant organs.
Dr. Zakharia is co-author of a study being presented at the ASCO Genitourinary Cancers Symposium examining this approach in patients with muscle-invasive bladder cancer, in which the cancer has grown into the bladder wall and typically requires surgery.
In the large international phase 3 clinical trial, nearly 800 patients were randomly assigned to receive either the combination therapy or traditional cisplatin chemotherapy before surgery.
The results showed meaningful improvement. The combination reduced the risk of cancer recurrence or progression by 47% and improved overall survival. About 55% of patients who received the therapy had no detectable cancer at surgery, compared with 32% in the chemotherapy group.
“That degree of complete response is significant,” says Dr. Zakharia. “It suggests we are improving outcomes and potentially leading to long-term remission for some patients.”
The treatment was generally well tolerated, with side effects considered manageable and often less burdensome than chemotherapy. Based on the findings, Dr. Zakharia says the combination may soon become standard therapy before surgery for patients eligible to receive cisplatin.
Improving outcomes in kidney cancer
In metastatic kidney cancer, today’s first-line treatments are significantly more effective than those available in the past. Many patients receive dual immunotherapy or a combination of targeted therapy and immunotherapy.
“These combinations shrink tumors in 60% to 70% of patients,” Dr. Zakharia says. “With certain immunotherapy combinations, 10-year follow-up data show that about 30% of patients with advanced disease and higher-risk features are alive and doing well. That was previously unheard of in metastatic kidney cancer.”
Despite these advances, many patients eventually experience disease progression. Response rates to second-line treatments drop to roughly 30% to 40%, making this an important focus of Dr. Zakharia’s research.
One study led by Dr. Zakharia combines high-dose selenium, which is a nutritional supplement being studied for its potential anticancer effects, with a standard targeted therapy. In an early-phase clinical trial involving patients whose cancer had already progressed on other treatments, the combination produced tumor shrinkage in about half of the participants, with some responses lasting more than two years. The results were published in Clinical Cancer Research in 2025.
“The results were encouraging, especially in a refractory setting where we typically see more modest response rates,” he says. A larger randomized trial is now being planned.
Mayo Clinic is also opening additional kidney cancer trials combing next-generation drugs with established treatments. Some evaluate entirely new medications being tested in patients for the first time. The goal is to improve response rates and extend survival while maintaining quality of life.
Clinical research leadership at Mayo Clinic
“We’re continuing to refine treatment approaches based on what we learn through research,” Dr. Zakharia says. “Mayo Clinic’s translational science and multidisciplinary teams make it possible to move discoveries from the laboratory to patient care more quickly.”
With multiple new studies underway in kidney and bladder cancer, Mayo Clinic continues to advance collaborative research aimed at improving long-term outcomes for patients.
