At the 2026 Genitourinary Cancers Symposium of the American Society of Clinical Oncology (ASCO GU 2026), held in San Francisco, leading experts from around the world gathered to present cutting-edge advances in urothelial carcinoma (UC). Key themes included antibody–drug conjugate (ADC) plus immunotherapy strategies for bladder preservation, clinical translation of liquid biopsy technologies, and deeper exploration of tumor molecular mechanisms. Oncology Frontier invited Professor Haige Chen from Renji Hospital, Shanghai Jiao Tong University School of Medicine, to interpret the major clinical trends and discuss opportunities and challenges for implementing these innovations in China.
Key Clinical Trends from ASCO GU 2026
Professor Chen emphasized that bladder cancer management is rapidly evolving toward precision medicine, organ preservation, and full-course management, with several landmark developments emerging.
One of the most important breakthroughs is the rise of ADC combined with immunotherapy in the perioperative setting for muscle-invasive bladder cancer (MIBC). The EV-304 phase III trial, building on earlier EV-303 data, directly compared enfortumab vedotin plus pembrolizumab against standard gemcitabine–cisplatin chemotherapy in cisplatin-eligible patients. The results were striking: the combination significantly improved event-free survival, overall survival, and pathological complete response (pCR).
The risk of recurrence, progression, or death was reduced by 47%, and mortality risk decreased by 35%. The pCR rate reached 55.8%, far exceeding the 32.5% seen with standard chemotherapy. This is the first phase III study demonstrating clear superiority of an ADC–immunotherapy combination over platinum-based chemotherapy in this population, effectively challenging the long-standing role of cisplatin as the backbone of neoadjuvant therapy.
Importantly, higher pCR rates also create new opportunities for bladder preservation strategies. However, safety remains critical, especially in earlier-stage patients. The study reported a slightly higher rate of grade ≥3 adverse events compared with chemotherapy, highlighting the need for careful perioperative management.
Another highly impactful study was RETAIN-2, which represents a new paradigm of precision stratification combined with drug-only bladder preservation. In this trial, treatment decisions were guided by next-generation sequencing (NGS). Patients with DNA damage repair mutations received intensified chemotherapy plus immunotherapy, and those achieving complete response entered an active surveillance strategy without radiotherapy.
A key innovation was the use of circulating tumor DNA (ctDNA) as a dynamic biomarker to assess treatment response and guide decisions. The study met its primary endpoint, with a two-year metastasis-free survival rate of 85% in patients under active surveillance. This demonstrates the feasibility of a fully personalized, non-surgical bladder preservation approach.
At the same time, ctDNA is reshaping postoperative management. Updated results from the IMvigor011 trial confirmed that ctDNA can guide adjuvant therapy decisions. Patients who remained ctDNA-negative after radical cystectomy achieved excellent outcomes without additional immunotherapy, avoiding overtreatment. In contrast, ctDNA-positive patients derived significant benefit from adjuvant atezolizumab, with a 41% reduction in mortality risk. This challenges the traditional “one-size-fits-all” approach to prolonged immunotherapy and establishes ctDNA as a central tool in perioperative decision-making.
Chinese innovation also stood out at the meeting. The domestically developed HER2-targeted ADC disitamab vedotin demonstrated strong efficacy in advanced urothelial carcinoma, with an objective response rate of nearly 55% and a median overall survival of 20 months. Notably, benefits were also observed in patients with low HER2 expression, underscoring the global competitiveness of Chinese-developed therapies.
Beyond MIBC, advances in non–muscle-invasive bladder cancer (NMIBC) were also notable. Surgical innovation, including robotic-assisted en bloc resection techniques, may improve precision and pathological assessment. Meanwhile, for very high-risk NMIBC patients who fail BCG therapy, new bladder-preserving strategies are emerging, including radiotherapy-based approaches and combinations of intravesical therapy with systemic immunotherapy.
Opportunities and Challenges for Clinical Implementation
Professor Chen highlighted that the rise of precision medicine presents both opportunities and challenges.
The most critical prerequisite for precision treatment is the standardized implementation of molecular testing. In the future, MIBC management will increasingly rely on multidisciplinary decision-making based on NGS results. Accurate identification of molecular subtypes and therapeutic targets will guide treatment selection, including eligibility for bladder preservation strategies.
At the same time, liquid biopsy technologies such as ctDNA and urinary tumor DNA (utDNA) must move from research into routine clinical practice. However, significant challenges remain. Currently, there is no unified standard for detection methods, sensitivity, interpretation, or reporting. This lack of standardization may lead to inconsistent results and affect clinical decisions.
Looking ahead, integrating multiple detection modalities may offer a solution. ctDNA is particularly effective for identifying systemic disease risk, while utDNA is more sensitive for detecting local bladder recurrence. Combining these approaches, potentially enhanced by artificial intelligence, could enable truly non-invasive and dynamic disease monitoring. This may even reduce the need for invasive cystoscopy and allow treatment intensity to be adjusted in real time.
The Evolving Role of Surgeons
One of the most profound shifts is the changing role of urologic surgeons. As systemic therapies become more effective and move earlier in the treatment course, the need for radical cystectomy may decrease.
However, rather than diminishing the role of surgeons, this transition redefines it. Surgeons are evolving from operators of the “scalpel” to leaders of the “molecular scalpel,” overseeing the entire treatment pathway—from molecular diagnostics and liquid biopsy interpretation to personalized therapy selection and organ-preserving strategies.
Even for patients who do not achieve complete response, combined approaches such as partial cystectomy and localized radiotherapy may still enable bladder preservation. This integrated, patient-centered approach represents the future direction of the field.
Conclusion
Overall, ASCO GU 2026 showcased a comprehensive transformation in bladder cancer care—from technological innovation and therapeutic breakthroughs to a fundamental shift in clinical philosophy.
As Professor Haige Chen emphasized, the next critical step is translating these advances into standardized clinical practice, ensuring that patients can benefit from precision, effective, and less invasive treatment strategies as soon as possible.
Professor Haige Chen
