Bladder Cancer

Gopa Iyer, MD, reviews early NEXUS-01 data evaluating the investigational anti–Nectin-4 ADC LY4052031, highlighting the importance of CYP2D6-guided dosing to optimize safety.

"Ultimately, integrating robust, disease-specific PROs into routine bladder cancer care represents a key step toward more truly patient-centered management," write the authors.

The NCCN recommends that clinicians consider using ctDNA-MRD testing to stratify risk and guide the use of adjuvant immunotherapy in patients who have not previously received an immune checkpoint inhibitor.

This decision marks the first approval of a PD-1 inhibitor plus antibody-drug conjugate regimen in the EU.

Eugene Pietzak, MD, highlights results from a phase 2 study of pembrolizumab plus BCG for patients with very high-risk, BCG-naive high-grade T1 NMIBC who declined upfront radical cystectomy.

Sandip Prasad, MD, discusses 3-year data from the phase 3 ENVISION trial evaluating mitomycin for intravesical solution for recurrent low-grade intermediate-risk non–muscle-invasive bladder cancer.

Abigail Keller, MD, shares findings showing that nadofaragene firadenovec is associated with increased urine production during instillation compared with gemcitabine/docetaxel.

The primary end point—12-month DFS rate—was 80% (40/50 evaluable patients; 95% CI, 0.67-0.89), with 2 patients pending assessment and 3 not evaluable.

"Together with the efficacy and safety results, these PRO findings support the overall benefit-risk profile of perioperative EV plus [pembrolizumab] as the new standard of care in this patient population," said Peter H. O'Donnell, MD.

Study investigator Gopa Iyer, MD, concluded that LY4052031 represents a promising next-generation Nectin-4 ADC with a distinct payload mechanism that may overcome EV resistance in mUC.

"These data help inform patient decision-making regarding adjuvant therapy and also point to a possible need for supportive services to help survivors after treatment," said Ronald C. Chen, MD, MPH, FASCO, FASTRO.

At a median follow-up of 42.8 months, median OS was 33.6 months (95% CI, 26.6–39.8) with EV+P (240 events/442 patients) vs 15.9 months (95% CI, 13.6–18.3) with chemotherapy (329 events/444 patients).

"Twenty-seven of 40 patients achieved a pCR amounting to a rate of 68%. Therefore, the null hypothesis could be rejected," said Richard Cathomas, MD.

Christof Vulsteke, MD, PhD, shares in-depth insights on the 3.5-year analysis of the EV-302 trial, evaluating enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma.

The approval is supported by data from the phase 3 POTOMAC trial.

The application is supported by data from the phase 3 KEYNOTE-905/EV-303 trial.

Mark D. Tyson II, MD, MPH, discusses findings from the phse 3b PATAPSCO study, evaluating durvalumab plus BCG for patients with BCG-naïve, high-risk NMIBC.

Vesta Bladder Risk Stratify Dx applies AI foundation models to H&E pathology slides obtained during routine clinical care to generate prognostic risk assessments.

The agency issued a PDUFA target action date of January 6, 2027.

The phase 1/2 ResQ133A-NMIBC trial (NCT06800963) is evaluating intravesical recombinant BCG in patients with BCG-naïve high-risk NMIBC across US sites, with safety as the primary end point and complete response and disease-free survival as secondary end points, building on European data showing 50% response rates and no dose-limiting toxicities in BCG-unresponsive disease.

Chad A. Reichard, MD, highlights real-world data presented at AUA 2026 on re-induction with nadofaragene firadenovec in patients with BCG-unresponsive non–muscle-invasive bladder cancer.

Adam B. Weiner, MD, is joined by Mary Beth Westerman, MD, FACS, to discuss the landmark CISTO trial—a large pragmatic study examining patient-reported outcomes among individuals with high-risk non–muscle invasive bladder cancer who underwent either bladder-sparing therapy or radical cystectomy.

"I think these data clearly support one year of durvalumab in combination with induction maintenance BCG as a potential new treatment for patients with BCG high-risk NMIBC with the appropriate shared decision-making conversation," said Neal D. Shore, MD, FACS.