A new real-world study is raising important questions about whether some patients with advanced bladder cancer may benefit from adding local treatment, such as surgery or radiation, after responding to systemic therapy with enfortumab vedotin (EV) and pembrolizumab (pembro).
While the findings are early and not yet practice-changing, they highlight a growing area of interest in bladder cancer care: whether treating the original bladder tumor after immunotherapy and targeted therapy could help certain patients live longer.
What is enfortumab vedotin plus pembrolizumab?
Enfortumab vedotin plus pembrolizumab (EV + P) is now considered a standard first-line treatment for many people with locally advanced or metastatic urothelial cancer, the most common type of bladder cancer.
This combination became a new standard after the landmark EV-302 trial showed it helped patients live longer compared with older chemotherapy approaches.
Doctors are still trying to understand an important next question: after a patient responds well to EV + P, should doctors also treat the bladder directly with surgery or radiation?
What did the new study find?
Researchers analyzed records from 459 patients with locally advanced or metastatic bladder cancer who received EV + P between 2019 and early 2025.
The average patient age was 73, and nearly 69% were male.
Researchers found that only 23.5% of patients went on to receive some type of bladder-directed local therapy after starting EV + P. These local treatments included:
- External beam radiation therapy (EBRT)
- Radical cystectomy (surgical removal of the bladder)
- Transurethral resection of bladder tumor (TURBT), a procedure used to remove bladder tumors through the urethra
Most local treatments happened within the first six months after starting systemic therapy.
Which treatment appeared to have the best outcomes?
Among the different local therapies studied, radical cystectomy appeared to be associated with the longest survival.
Patients who underwent cystectomy had not yet reached a median overall survival at the time of analysis, with several patients still alive beyond 600 days. By comparison:
- Patients who received no local therapy had a median overall survival of 204 days
- Patients who underwent TURBT had a median overall survival of 316 days
- Patients who received radiation therapy had a median overall survival of 217 days
Researchers stressed that these findings don’t prove surgery itself caused better survival.
Patients healthy enough to undergo surgery may already have had more favorable disease characteristics, better responses to treatment, or fewer metastatic sites. This is known as “selection bias,” and it is a major limitation of retrospective studies like this one.
Why are doctors being cautious about these findings?
Although the results are encouraging, experts emphasize that this study was retrospective, meaning researchers looked back at existing medical records rather than testing a treatment strategy in a controlled clinical trial.
Because of that, the study cannot definitively show that local therapy improves survival.
The analysis also had several limitations, including:
- Short follow-up time
- Missing clinical details
- Potential selection bias
- Use of overall survival rather than cancer-specific survival
- The possibility that healthier patients were more likely to receive surgery
Dr. Betty Wang, the study’s first author, said the findings should be considered “hypothesis-generating rather than practice-changing.”
Outside experts echoed that caution. Stronger prospective data is still needed before aggressive approaches like radical cystectomy become standard for patients who initially present with metastatic disease.
What does this mean for patients?
For patients responding well to EV + P, this study suggests there may be value in discussing whether additional local therapy could play a role in their treatment plan.
However, these decisions are highly individualized. Factors that may influence whether local therapy is considered include:
- How well the cancer responded to systemic treatment
- The location and extent of metastatic disease
- Overall health and surgical fitness
- Whether metastatic tumors can also be treated or controlled
- Patient goals and preferences
This is why multidisciplinary care is especially important. Medical oncologists, urologic oncologists, radiation oncologists, and surgeons may all help determine the best approach for a specific patient.
Clinical trials are already exploring this question
Several ongoing studies are trying to better define the role of local therapy after EV-pembro.
These include:
- EV-ECLIPSE trial, which is studying whether EV + P can shrink tumors before surgery
- CONSOLIdATE-1 study, which is evaluating radical cystectomy after response to EV-based treatment in selected patients with advanced disease
Researchers are also interested in using biomarkers like circulating tumor DNA (ctDNA) to help identify which patients may benefit most from consolidative therapy in the future.
The bottom line
This study highlights a growing interest in combining systemic therapy with local treatment for advanced bladder cancer. While only a minority of patients currently receive bladder-directed therapy after EV + P, those who underwent cystectomy appeared to have longer survival in this analysis.
Still, experts caution that these results should not yet change standard practice. More prospective clinical trials are needed to determine whether surgery or radiation truly improves outcomes after EV + P and which patients are most likely to benefit.
To learn more about bladder cancer, view our full webinar discussion with medical oncologist Dr. Elizabeth Plimack.
