For patients with non-muscle invasive bladder cancer (NMIBC), transurethral resection of bladder tumor (TURBt) and intravesical instillation remain the mainstays of treatment. However, a subset of high- or very high-risk patients still face substantial recurrence risk and may ultimately require radical cystectomy. In recent years, alternative intravesical strategies—beyond BCG alone—have drawn increasing attention, particularly with the emergence of novel combinations involving targeted and immune-based therapies. At the 2025 European Association of Urology (EAU25) Confrence, a study led by Professors Dingwei Ye and Yijun Shen was selected for oral presentation. The research, conducted by their team at Fudan University Shanghai Cancer Center, explored the use of the HER2-targeted antibody-drug conjugate RC48 in combination with BCG for patients with very high-risk NMIBC. In this exclusive interview with UroStream, Professors Ye and Shen share insights into their latest findings and broader trends at EAU25.Professor Dingwei Ye: Greetings to all readers of UroStream. I’m honored to have this opportunity to connect with Professor Yijun Shen during the EAU 2025 Confrence. As one of the most prestigious global gatherings in urology, the EAU Confrence—now in its 40th edition continues to grow in scale and impact. There’s a wealth of content here worth learning from. Professor Shen is part of our urothelial carcinoma team, and I’d like to begin by asking him to share his reflections on attending this year’s Confrence.
Professor Yijun Shen: Hello to the audience of UroStream. I’m very pleased to join this conversation from the 40th European Association of Urology (EAU) Confrence. As everyone knows, the EAU is one of the world’s most influential events in urology, attracting widespread participation from specialists across the globe. The program is rich and diverse, including keynote lectures, expert debates, live surgical demonstrations, and in-depth exchanges.
In recent years, I’ve clearly seen more and more Chinese urology experts stepping into the global spotlight at meetings like EAU and other international forums. Their presence and contributions are growing stronger year by year. This year marks a new milestone, with a record number of Chinese scholars presenting oral reports and engaging in high-level discussions. It’s a testament to the collective effort of national academic societies and colleagues across China. We are making real progress in clinical research, urologic oncology, stone disease, and more—and our voice on the global stage is louder than ever.
Professor Dingwei Ye: At this year’s EAU meeting, Professor Shen presented our team’s study on the use of RC48 in combination with BCG for HER2-expressing high-risk NMIBC. Could you share the main findings and clinical significance of this work with our colleagues at home?
Professor Yijun Shen: NMIBC is one of the most common types of bladder cancer that we encounter and treat in daily urologic practice. Despite recent advances, many challenges remain—particularly the high recurrence rate in high-risk cases. Even with traditional BCG or chemotherapy instillation, over half of patients still experience disease relapse.
To address this issue, we conducted a prospective single-center study enrolling patients with very high-risk HER2-expressing NMIBC (IHC 1+/2+/3+), including two subgroups: Group A (carcinoma in situ or incompletely resected tumors) and Group B (completely resected papillary tumors). Patients received intravenous RC48 combined with intravesical BCG instillation.
In terms of efficacy, the 3- and 6-month complete clinical response (cCR) rates reached 100%, and the 6-month event-free survival (EFS) rate for papillary tumor patients also reached 100%. These are highly encouraging short-term results. As for safety, the regimen was well tolerated. In our study, only two patients experienced grade ≥3 adverse events: one case of hematuria caused by BCG and one case of grade 3 peripheral neuropathy.
Overall, the combination of intravenous RC48 and BCG demonstrated promising short-term efficacy and good tolerability. For patients unwilling or unable to undergo radical cystectomy, this may represent a potential alternative therapeutic strategy in the future.
Professor Dingwei Ye: Thank you, Professor Shen, for your insightful sharing. I believe our urologic oncology team at Fudan University Shanghai Cancer Center has always maintained a dual focus—on clinical care and cutting-edge research. Your presentation on the application of ADC combined with BCG for high-risk NMIBC exemplifies this. Of course, the use of RC48 requires HER2 testing, which further promotes the refinement of molecular subtyping and precision treatment strategies for bladder cancer. Were there any other novel therapeutic approaches presented at this year’s EAU meeting for the treatment of high-risk NMIBC patients? After all, beyond BCG and a few chemotherapy instillations, options remain limited and the risk of recurrence persists.
Professor Yijun Shen: Thank you for the excellent question, Professor Ye. Indeed, during the bladder cancer oral sessions at this year’s EAU Confrence—especially those focused on non-muscle invasive bladder cancer—we saw exciting developments. For patients who are unresponsive to BCG, two late-breaking abstracts (LBAs) presented promising intravesical therapies that caught wide attention.
The first was the Phase III BOND-003 trial evaluating the intravesical oncolytic virus therapy Cretostimogene grenadenorepvec in BCG-unresponsive high-risk NMIBC and CIS (Cohort C). The results were impressive, with a complete response (CR) rate of 75.5% (83/110), a median duration of response of 27.9 months, and 97.3% (107/110) of patients avoiding progression to MIBC within 12 months. No grade ≥3 adverse events were reported, indicating strong efficacy and safety.
The second was a Phase I study of RAG-01, a small activating RNA (saRNA) therapy delivered via bladder instillation for BCG-refractory NMIBC. The dose-escalation design showed no dose-limiting toxicities (DLTs) or grade ≥3 adverse events. Among the limited cases, CR in CIS was 66.7% (2/3) and the 3-month disease-free survival (DFS) for papillary tumors was also 66.7% (2/3).
Beyond these two studies, the field is exploring a variety of strategies—including BCG in combination with immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and IL-15 agonists. Some of these were also presented at this year’s EAU meeting. Overall, there’s active global and domestic research in localized therapies for high-risk NMIBC, particularly for patients with very high risk. These approaches represent the current and future direction of the field.
As we know, BCG has long been a cornerstone of NMIBC treatment, and domestic experts have accumulated significant clinical experience. While short-term outcomes with BCG are generally favorable, about 50% of patients relapse in the long term, with 10–20% progressing to more advanced disease. Therefore, identifying strategies to delay recurrence and reduce the risk of progression remains a top research priority for this patient population.
Professor Dingwei Ye: At this year’s EAU Confrence, one of the plenary sessions dedicated to bladder cancer centered around several clinically debated topics. For example, one major question was: Is BCG still the best treatment option for high-risk NMIBC? Or even more provocatively—Can we abandon BCG altogether? I’d like to hear your perspective on these questions, Professor Shen, and how they align with the latest research presented at EAU.
Professor Yijun Shen: On the very first morning of this year’s EAU Confrence, there was a truly engaging session featuring six debates on bladder cancer. The discussions were intense, with participating experts well-prepared, citing the most up-to-date evidence and innovative studies. One of the focal debates revolved around BCG therapy—particularly in patients who are unresponsive to it.
In my opinion, BCG remains the cornerstone of treatment for high- and very-high-risk NMIBC. It’s a therapy that has been used in clinical practice for over 30 or even 40 years, and in China especially, we’ve accumulated considerable experience—some centers have been administering BCG instillations for more than a decade. For many patients, BCG remains the most effective intravesical therapy available.
That said, BCG shortages are a global challenge, and we see similar issues domestically due to cost and accessibility. This raises an important question: What alternatives can we explore when BCG isn’t available? One of the debates this year, as well as several studies presented, highlighted new, more accessible alternatives. For instance, sequential intravesical instillation with traditional chemotherapy agents—such as gemcitabine plus docetaxel—has garnered attention. A prospective study presented at EAU reported promising short-term efficacy: the median high-grade disease-free survival (HG-DFS) was 18 months, and the 1-year HG-DFS rate was 67%. Importantly, this regimen demonstrated a better safety profile than BCG, with only one serious adverse event reported.
Moreover, during the debate, some experts questioned whether it’s time to let go of BCG and whether newer agents might replace it. The consensus, however, was clear: BCG will remain irreplaceable in the coming years. The key lies not in abandoning BCG, but in better identifying which patients truly benefit from it. This is where emerging technologies like liquid biopsy and artificial intelligence come into play—helping us stratify patients and personalize therapy more precisely. That direction of inquiry is what many experts consider critical, both now and for the foreseeable future.
Professor Dingwei Ye: NMIBC is a relatively early-stage form of bladder cancer. With TURBt and intravesical therapy, many patients can maintain bladder function for a long time, enjoying a better quality of life compared to those undergoing radical cystectomy. Therefore, early diagnosis and treatment are key to improving outcomes and preserving quality of life for bladder cancer patients. To this end, our team at Fudan University Shanghai Cancer Center has led the development of several national guidelines and consensus documents, including the Expert Consensus on Early Diagnosis and Treatment of Bladder Cancer (2024 edition), the Chinese Multidisciplinary Bladder-Preserving Treatment Consensus for Bladder Cancer (2022 edition), and the Expert Consensus on Intravesical Therapy for NMIBC (2021 edition). These reflect the collective experience and perspectives of Chinese clinicians. Professor Shen, based on your experience attending the EAU Confrence and engaging with European and American experts, what differences do you perceive between China and the West in terms of bladder cancer management strategies or treatment philosophy?
Professor Yijun Shen: Under your leadership, Professor Ye, our department has indeed made great strides in bladder cancer research, particularly through involvement in national guideline development. As you mentioned, our efforts focus primarily on a few key areas.
First is the advancement of early diagnosis and treatment. We are actively exploring the use of innovative biomarkers in urine and blood for the early detection of bladder cancer, especially for monitoring recurrence post-surgery or during bladder-preserving treatment. Even after radical cystectomy, we aim to incorporate biomarkers—such as ctDNA and urinary markers—for post-operative surveillance. Overall, China has made impressive progress in this field. Many of our peers are now investigating methylation markers, DNA/RNA profiles, and proteomic biomarkers. In terms of scientific rigor, our work is on par with the West. However, the most critical challenge is designing high-quality clinical studies. Whether in diagnostics, treatment, or surveillance, we must focus on meticulous trial design. Moreover, as we adopt novel therapies, we need to learn how to integrate biomarkers effectively into clinical decision-making. That’s where we can learn from the West—how to better structure trials that guide therapeutic decisions through biomarker integration.
Second, we’re also pushing forward bladder-preserving strategies and systemic treatments for advanced disease. Under your guidance, and with support from national peers, we’ve been involved in pioneering work with novel therapies. For instance, in the second- and third-line treatment of advanced urothelial carcinoma, we’ve trialed a first-in-class EGFR×HER3 bispecific ADC. Last year, we presented the findings at ESMO. Now, we are launching a national multicenter study. These therapies are truly innovative, and in many cases, globally first-in-class, highlighting China’s capacity for cutting-edge drug development. Through this work, we aim to elevate the voice of Chinese pharmaceutical innovation on the international stage. During this year’s EAU Confrence, many global colleagues showed strong interest in our novel agents, and expressed a desire to participate in future international collaborative trials.
Professor Dingwei Ye
Chief Physician, Professor, Doctoral Supervisor Vice President of Fudan University Shanghai Cancer Center Leader of the Department of Urology, Chief Expert of Urologic Oncology MDT, Director of the Shanghai Urologic Oncology Research Institute, and Director of the Fudan University Prostate Cancer Research Institute. Chairman of the Chinese Anti-Cancer Association Committee on Male Genitourinary Tumors (CACA-GO), Chairman of the Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Expert Committee, Chairman of the Urology Committee of the China Primary Health Care Foundation, Former Chairman of the CACA Genitourinary Tumor Committee (CACA-GU), Vice Chair of the Oncology Group of the Chinese Urological Association (CUA), and Chairman of the Chinese Prostate Cancer Research Collaborative Group (CPCC). Also serves as Vice Chairman of the CSCO Urothelial Carcinoma Committee, CSCO Renal Cancer Committee, and CSCO Immunotherapy Committee.
He has led over 60 national and provincial-level research projects, and has published over 700 papers as first or corresponding author in journals such as Nature Genetics, Journal of Clinical Oncology, Lancet Oncology, and European Urology.
As the first contributor, he has received numerous prestigious awards, including:
- Two First Prizes for Scientific and Technological Progress from the Shanghai Municipal Government
- First and Second Prizes from the Ministry of Education for Scientific and Technological Achievements
- First Prize of the Shanghai Medical Science and Technology Award
- Second Prize of the Chinese Medical Science and Technology Award
- First and Second Prizes of the Chinese Anti-Cancer Association Science and Technology Award
He has been recognized as a National Health Commission Outstanding Young and Middle-Aged Expert with Significant Contributions, recipient of the Wu Jieping Urological Medicine Award, the WuXi AppTec Life Chemistry Research Award, Shanghai Leading Talent, Excellent Academic Leader of Shanghai, Shanghai Master Craftsman, “Shanghai Good Doctor,” and National Advanced Health and Family Planning System Worker. He also enjoys the Special Government Allowance from the State Council of China.
Professor Yijun Shen
Fudan University Shanghai Cancer Center
Professor Shen is Chief Physician in the Department of Urology at Fudan University Shanghai Cancer Center, holds a doctorate in medicine, and is a master’s supervisor.
He has served as a visiting scholar at MD Anderson Cancer Center and the University of Texas Medical School in the United States.
His professional roles include:
- Senior Talent Evaluation Expert, National Health Commission of China
- Member, Urothelial Carcinoma Expert Committee, Chinese Society of Clinical Oncology (CSCO)
- Member, Bladder Cancer Group, Committee on Genitourinary Tumors, Chinese Anti-Cancer Association (CACA)
- Member, Urologists Branch, Shanghai Medical Doctor Association
- Member, Urologic Oncology Committee, Shanghai Anti-Cancer Association
- Expert Inspector, Shanghai Urology Clinical Quality Control Center
- Editorial Board Member, Journal of Clinical Oncology (Chinese edition, Urology section)
- Corresponding Editorial Board Member, Chinese Journal of Andrology
Professor Shen has long been dedicated to the diagnosis, prevention, and multidisciplinary treatment of genitourinary cancers. He is particularly skilled in laparoscopic and da Vinci robot-assisted radical cystectomy, sexual function-preserving radical cystectomy, orthotopic neobladder reconstruction, and bladder-preserving combination therapies.
He has led research projects funded by the National Natural Science Foundation of China, the Shanghai Natural Science Foundation, major clinical research programs from Shanghai Shenkang Hospital Development Center, and the Shanghai Municipal Health Commission. His research findings have been incorporated into the NCCN Guidelines for the diagnosis and treatment of bladder cancer.
He is the chief editor of the book Invasive Bladder Cancer and a contributing author to chapters on bladder tumors in Practical Surgery and Practical Oncological Surgery.
Reference
[1]Yijun Shen, et al.Preliminary efficacy and safety of Disitamab Vedotin combined with Bacillus Calmette-Guérin in the treatment of high-risk non-muscle invasive bladder cancer with HER2 expression: A prospective, open label, single-center study.EAU25,Abstract A0795
[2]Dinney C,et al.Updated Clinical & Translational Results: BOND-003 Cohort C- A Phase 3, Single-Arm Study of Intravesical Cretostimogene Grenadenorepvec for High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer with Carcinoma In Situ.EAU25,Abstract LB12
[3]Krieger L,et al.First-in-human study of RAG-01, a novel small activating RNA therapeutic in BCG failure Non-Muscle Invasive Bladder Cancer (NMIBC) patients.EAU25,Abstract LB11
[4]Pijpers O.M., et al.Sequential intravesical gemcitabine and docetaxel in heavily pretreated patients with recurrent high-grade non-muscle invasive bladder cancer – a prospective cohort study.EAU25,Abstract A0792
