Trimodality therapy (TMT)is a well-established bladder-sparing strategy for patients with muscle-invasive bladder cancer (MIBC). However, limitations remain for patients intolerant to chemotherapy and in monitoring post-treatment recurrence. Professors Haige Chen and Ruiyun Zhang of Renji Hospital, Shanghai Jiao Tong University School of Medicine, have long focused on MIBC research. This year, nine of their studies were accepted at the EAU Congress. UroStream invited Professors Chen and Zhang to share their insights on emerging approaches, including chemotherapy-free strategies combining the domestic ADC drug RC48 with PD-1 inhibitors, the value of utDNA in non-invasive monitoring, AI-based molecular subtyping, and major takeaways from the congress.1. RC48 Plus PD-1 Inhibitor: A New Bladder-Sparing Strategy for HER2-Positive MIBC
Prof. Haige Chen：Bladder preservation for MIBC patients has become a key research focus. While TMT is the standard approach, we’ve observed that some patients experience adverse reactions to chemotherapy—including renal impairment, bone marrow suppression, and gastrointestinal toxicity—which compromise both adherence and tolerability.
The introduction of immune checkpoint inhibitors, particularly PD-1 antibodies, has broadened treatment options for urothelial carcinoma. Bladder cancer, along with lung cancer and melanoma, was among the first tumor types to benefit from PD-1-based therapy. However, responses to PD-1 monotherapy remain suboptimal in some patients.
Our research identified a high prevalence of HER2 expression (IHC ≥1+) among MIBC patients. The emergence of the domestically developed anti-HER2 ADC drug RC48 brings new hope. We perform TURBT for diagnosis and, if HER2 is highly expressed, proceed with a combination of RC48 and PD-1 inhibitors to achieve bladder preservation.
In addition, we’re exploring radiotherapy combined with anti-HER2 and immunotherapy as a novel, chemotherapy-free bladder-sparing approach. Phase I safety data from the DECIDING study showed good tolerability and high CR rates in patients treated with RC48 plus toripalimab. A Phase II multicenter study is underway, and we look forward to sharing those results with the community soon.
2. utDNA in Bladder-Sparing Monitoring: A Non-Invasive Breakthrough
Prof. Ruiyun Zhang：Thank you to UroStream for the opportunity. Under the leadership of Prof. Chen, nine of our team’s studies were accepted at this year’s EAU Congress, including mini oral and EGPT formats. One major oral presentation highlighted the clinical application of utDNA—a liquid biopsy tool—in MIBC bladder-sparing management.
As Prof. Chen noted, a critical challenge in bladder preservation is determining whether patients achieve pathological complete response (pCR) after neoadjuvant therapy. Traditional imaging, cystoscopy, and urine cytology only assess for clinical complete response (cCR), and it remains unclear how many of those patients truly reach pCR without undergoing radical cystectomy.
Our early findings show that patients who achieve utDNA clearance after neoadjuvant or bladder-sparing therapy often also achieve ypCR, suggesting that utDNA could serve as a reliable indicator of therapeutic success.
Another key application is early recurrence detection. Identifying recurrence early enables timely salvage cystectomy, which may improve prognosis. utDNA offers a non-invasive, long-term monitoring method with less patient burden than cystoscopy or imaging, helping to guide early intervention when needed.
3. Harnessing AI for MIBC Molecular Subtyping and Personalized Therapy
Prof. Haige Chen：Leading urology centers like MD Anderson Cancer Center and Karolinska University Hospital have used TCGA data to classify MIBC into molecular subtypes. We initially kept pace with these efforts, but considering the cost and feasibility challenges of sequencing every patient in China, we shifted from RNA-based to immunohistochemistry (IHC)-based methods in 2016.
MIBC can be broadly divided into basal and luminal subtypes. Luminal tumors account for about 70% of cases, are less aggressive, and respond well to treatment. Basal tumors, on the other hand, are more aggressive and require timely intervention.
Our center performs H&E staining followed by IHC to classify TURBT specimens and guide treatment. However, this process takes about two weeks and depends on skilled pathologists, which introduces variability.
Over the past decade, we’ve accumulated a large database of IHC and H&E results. By training AI models with this data, we’ve developed an intelligent system capable of automating subtype classification. This significantly accelerates treatment decision-making and ensures that patients with basal-type disease receive timely comprehensive treatment, including targeted and immune therapies.
4. MIBC Research Trends at EAU25: Toward Precision and Preservation
Prof. Ruiyun Zhang：As Prof. Chen mentioned, this year’s EAU Congress highlighted a clear shift in focus toward urothelial carcinoma, with MIBC taking center stage among urologic cancers. I’d like to emphasize three key trends:
First, AI applications in MIBC are expanding rapidly. From early diagnosis and drug screening to response prediction, AI is playing a growing role. Large language models are even being used to support multidisciplinary team (MDT) decisions, marking an exciting new direction.
Second, significant treatment breakthroughs were presented. The SunRISe-4 study, highlighted in the Late-Breaking Abstract session, reported promising early results for TAR-200 plus PD-1 inhibitors in the neoadjuvant setting. Meanwhile, the ongoing TAR-210 study is evaluating the efficacy of this novel intravesical delivery system in FGFR-mutant MIBC. As data accumulate, intravesical plus systemic combination therapies will likely gain broader application.
Third, the role of molecular biomarkers is becoming more central. This includes tissue-, urine-, and blood-based biomarkers, which featured more prominently in this year’s sessions. The EAU Congress even organized a dedicated poster session titled Urothelial Carcinoma – Basic Research and Trials: Muscle Invasive and Metastatic Urothelial Cancer. Two of our urine-based studies were included, reflecting growing interest in real-time, non-invasive monitoring tools that can inform clinical decision-making while reducing toxicity and preserving organ function.
Professor Haige Chen Chief Physician, Doctoral Supervisor Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Senior Visiting Scholar, KU Leuven, Belgium
- Deputy Director of Urology, Renji Hospital
- Executive Director of Urology, Renji South Campus
- Head of the Bladder Cancer Group, Renji Hospital
Academic and Professional Affiliations:
- Member, Oncology Subcommittee, Chinese Urological Association
- Member, Shanghai Branch, Chinese Urological Association
- Vice-Chair, Oncology Subcommittee, Shanghai Branch, Chinese Urological Association
- Member, Urology Subcommittee, Chinese Health Promotion Association
- Member, Urology Group, Endoscopic and Minimally Invasive Technology Branch, China Association for Medical Equipment
- Member, International Bladder Cancer Network (IBCN)
- Founding Member, China Bladder Cancer Alliance
- Peer Reviewer, National Natural Science Foundation of China
- Reviewer for journals including Oncology Letters, BMC Cancer, and Urology
Professor Ruiyun Zhang Attending Physician, MD (trained in France) Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Head of the Bladder Cancer Clinical Team, South and West Campuses, Renji Hospital
- Quality Control Expert, National Clinical Drug Trial Center, Renji Hospital
Talent Recognition Programs:
- “Morning Star” Young Scientist Program, Shanghai Science and Technology Commission
- “Medical Rising Star” Program, Shanghai Municipal Health Commission
Academic and Professional Affiliations:
- Member, Bladder Cancer Committee (Integrative Medicine), Chinese Anti-Cancer Association
- Youth Member, Disease Prevention and Control Branch, Chinese National Health Association
- Committee Member and Corresponding Editorial Board Member, Asian Robotic Radical Cystectomy Consortium (ARARC)
- International Member, International Bladder Cancer Network (IBCN)
- Academic Secretary, Editorial Board of BJUI Chinese Edition
- Peer Reviewer for journals including Oncology Letters, BMC Cancer, and Oncology and Translational Medicine
Awards:
- National Champion, First “Tan Jie Daren” Case Competition for Young Urologists in China
- National Champion, First “Rongchang Cup” National Urothelial Carcinoma Case Presentation Competition
