Perioperative Immunotherapy Reshapes Genitourinary Cancer Treatment Landscape

At the Binaytara 2026 Tucson Annual Conference on Advances in Hematology and Oncology, oncologists gathered to discuss a fundamental shift in how they treat three of the most common cancers in men. The conversation, led by Wish Dhillon, a medical oncologist at Arizona Cancer Center/Honor Health, centered on a single theme: the addition of immunotherapy and targeted agents to existing treatment regimens is beginning to reshape outcomes in ways that demand immediate changes to clinical practice.

The most striking finding came from bladder cancer research. The KEYNOTE-B15 trial, also known as EV-304, tested a combination of enfortumab vedotin and pembrolizumab given before surgery in patients with muscle-invasive bladder cancer who could tolerate cisplatin. The results were substantial. The new combination reduced the risk of disease progression or death by 47 percent compared to the standard neoadjuvant approach of gemcitabine and cisplatin. More concretely, the median event-free survival was not yet reached in the treatment group, while the control group saw a median of 48.5 months. Overall survival also improved, with a 35 percent reduction in the risk of death. Perhaps most visibly, the rate of pathologic complete response—meaning no cancer cells remained in the surgical specimen—jumped from 32.5 percent to 55.8 percent. This trial, Dhillon noted, was the clear highlight of the session, and for good reason: it represents the kind of improvement that oncologists can implement immediately in their clinics.

Prostate cancer management is moving in a different but equally consequential direction. Two major trials presented at the conference—TALAPRO-3 and PROTEUS—suggest that the field is moving toward earlier, more aggressive intervention guided by genetic testing. TALAPRO-3 showed that men with metastatic castration-sensitive prostate cancer whose tumors carried homologous recombination repair mutations benefited from early treatment with talazoparib plus enzalutamide, with a roughly 52 percent reduction in the risk of progression. The practical implication, Dhillon emphasized, extends beyond this single drug combination. If oncologists are going to offer biomarker-directed intensification at the time of metastatic diagnosis, then every patient diagnosed with metastatic prostate cancer should receive next-generation sequencing—both germline testing and tumor or circulating tumor DNA analysis—at that initial visit, not months or years later when disease has progressed further.

The prostate cancer landscape also revealed unsettled questions. Two different approaches to intensifying treatment in men with metastatic castration-sensitive disease are now available, but no direct comparison exists. PSMAddition added the radiopharmaceutical Lu-PSMA-617 to androgen deprivation therapy plus an androgen receptor pathway inhibitor in PSMA-positive patients, improving radiographic progression-free survival by 28 percent, though overall survival data remain immature. This sits alongside chemotherapy-based triplets like ARASENS, which showed a 32 percent reduction in the risk of death. Without a head-to-head trial, oncologists must make clinical judgments about which approach suits which patient.

Perioperative therapy—treatment given before and after surgery—is emerging as another frontier. The PROTEUS trial demonstrated that adding apalutamide plus androgen deprivation therapy around the time of radical prostatectomy deepened the pathologic response to surgery and improved metastasis-free survival. Yet the field has not yet settled how to implement this in routine care: which patients should receive it, for how long, and how it compares to radiation-based approaches for high-risk disease remain open questions being worked out in real practice and in evolving treatment guidelines.

Kidney cancer adjuvant therapy—treatment given after surgery to prevent recurrence—is also intensifying, though with important caveats about toxicity. The LITESPARK-022 trial tested belzutifan, a hypoxia-inducible factor inhibitor, combined with pembrolizumab after surgery, compared to pembrolizumab alone. The combination improved disease-free survival at 24 months from 73.7 percent to 80.7 percent, a meaningful but not dramatic gain. However, the combination produced higher rates of grade 3 or worse toxicity, and overall survival data remain immature. This is precisely the kind of result that demands careful clinical judgment: the benefit is real, but it comes with costs that must be weighed for each individual patient.

Across all three cancer types, a pattern emerges. The trials presented at Binaytara 2026 show that adding immunotherapy or targeted agents to existing approaches can improve outcomes, sometimes substantially. But implementation is not straightforward. Bladder cancer has a clear winner ready for adoption. Prostate cancer requires a commitment to universal genetic testing and a willingness to make treatment decisions earlier in the disease course. Kidney cancer offers a modest benefit paired with increased toxicity. The oncologists in the room understood that the next phase of this work—translating these trials into practice—will require as much clinical wisdom as the research itself demanded.