The 2026 European Association of Urology Annual Congress (EAU26), held in London, brought together leading experts from across the globe to discuss the latest advances in urology. Among the highlights, the final results of the HOPE-03 study, led by Prof. Peng Zhang and his team from West China Hospital, Sichuan University, were presented as an oral session, drawing significant international attention. In an exclusive interview, Prof. Zhang shared key efficacy outcomes, therapeutic advantages, safety considerations, and the future clinical implications of this innovative approach.
Promising Efficacy in the Neoadjuvant Setting
The HOPE-03 study is a multicenter, single-arm, open-label phase Ib/II trial investigating disitamab vedotin in combination with tislelizumab as neoadjuvant therapy for HER2-expressing locally advanced muscle-invasive bladder cancer (MIBC).
The final analysis includes complete two-year follow-up data, with a particular focus on clinical complete response (cCR) rather than the traditional pathological complete response (pCR). This distinction is important, as the primary goal of the study is bladder preservation rather than immediate radical cystectomy.
A stringent definition of cCR was applied, requiring the absence of detectable tumor on imaging, negative urine cytology, and complete tumor clearance confirmed by transurethral resection. Based on these criteria, the overall cCR rate reached 71.7%.
For patients achieving cCR, subsequent consolidation with radiotherapy plus immunotherapy was administered. At two years, the bladder preservation rate in this subgroup reached an impressive 95.5%, representing a highly encouraging outcome. Longer follow-up will be required to fully assess durability, long-term functional outcomes, and survival benefits.
Advantages Over Conventional Chemotherapy
Compared with platinum-based neoadjuvant chemotherapy, the combination of ADC and immunotherapy offers distinct advantages, particularly in terms of tolerability and treatment completion.
In real-world practice, nearly half of patients with MIBC are unable to receive cisplatin due to renal impairment, comorbidities, or advanced age. Even among eligible patients, treatment-related toxicities such as gastrointestinal effects and myelosuppression often limit completion of planned chemotherapy cycles.
By contrast, the disitamab vedotin plus immunotherapy regimen demonstrates improved tolerability, enabling patients to complete longer treatment courses. This translates into more effective tumor downstaging and, in many cases, complete eradication of residual tumor in surgical specimens.
Importantly, this enhanced tumor control in the neoadjuvant phase creates an opportunity to transition selected patients toward bladder-preserving strategies. The HOPE-03 study exemplifies this paradigm by integrating neoadjuvant therapy with subsequent radiotherapy and immunotherapy as consolidation, forming a comprehensive, organ-preserving treatment pathway.
Safety Profile and Perioperative Management
The safety profile observed in HOPE-03 is consistent with prior clinical experience for both disitamab vedotin and immune checkpoint inhibitors. No unexpected safety signals were identified, and the overall incidence of treatment-related adverse events was comparable to that seen with conventional neoadjuvant chemotherapy followed by surgery.
Effective perioperative management remains essential. This includes comprehensive baseline assessment and continuous monitoring throughout treatment, covering liver and renal function, metabolic parameters, thyroid function, and cardiac biomarkers. Applying established frameworks for immune-related adverse event management allows for early detection and timely intervention, thereby maintaining treatment adherence and safety.
Toward Clinical Practice Integration
While the results of HOPE-03 are highly encouraging, Prof. Zhang emphasized that adoption into standard-of-care guidelines requires robust evidence from larger, randomized trials with longer follow-up.
The current study, as a phase Ib/II exploratory trial, provides strong signals of efficacy and safety but must be further validated in broader patient populations. Nonetheless, it represents an important step toward redefining treatment paradigms in MIBC.
The concept of neoadjuvant ADC plus immunotherapy followed by individualized bladder-preserving strategies aligns closely with evolving patient priorities. Increasingly, patients seek not only prolonged survival but also preservation of organ function and quality of life.
As evidence continues to accumulate, this approach has the potential to become a transformative option for selected patients with HER2-expressing MIBC, offering a meaningful balance between oncologic control and functional preservation.
Prof. Peng Zhang
