Bladder-preserving treatment is an important therapeutic strategy for patients with muscle-invasive bladder cancer (MIBC), aiming to maintain bladder function while avoiding radical cystectomy. In recent years, this approach has become a major focus of clinical research, with multiple emerging strategies. Oncology Frontier invited Professor Yiping Zhu from Fudan University Shanghai Cancer Center to discuss treatment options after Bacillus Calmette–Guérin (BCG) failure, innovations in bladder-sparing techniques, and evolving clinical paradigms.
Q1
Oncology Frontier: After failure of BCG intravesical therapy in MIBC, there remains a significant unmet clinical need. What directions should future treatment development focus on?
Professor Yiping Zhu: Patients who fail BCG therapy represent a major clinical challenge. Traditionally, these patients would proceed to radical cystectomy. However, over the past 5–10 years, several new therapeutic strategies have emerged.
Currently, immunotherapy has been approved by the U.S. FDA. Based on the KEYNOTE-057 study, intravenous PD-1 inhibitors have demonstrated promising efficacy. More recent studies suggest that subcutaneous PD-1 antibodies combined with repeat BCG instillation can also achieve favorable outcomes.
In addition, novel agents are under development, including oncolytic viral therapies. These therapies deliver adenoviruses into bladder cancer cells, leading to tumor cell lysis. The BOND-007 study has shown that adenovirus- or herpes simplex virus–based therapies can significantly improve outcomes in patients with BCG failure.
At our center, we have also conducted clinical studies using intravesical administration of novel antibody–drug conjugates (ADCs) combined with PD-1 inhibitors given either subcutaneously or intravenously, with encouraging results.
Another important issue is the shortage of BCG. Alternative strategies such as hyperthermic intravesical therapy or device-assisted instillation have shown some efficacy. Looking ahead, combination approaches that integrate intravesical therapy with systemic or subcutaneous treatment may become the standard. For example, in the SunRISe program, drug-delivery systems such as TAR-200 and TAR-210 can continuously release agents like gemcitabine or the FGFR inhibitor erdafitinib within the bladder. Compared with intermittent instillation, continuous drug delivery may offer superior therapeutic outcomes.
At the same time, treatment philosophy has evolved significantly. Instead of pursuing more extensive surgery, the field is shifting toward organ and function preservation. For example, two large phase III trials have demonstrated that extended lymph node dissection during radical cystectomy does not improve survival, supporting a more tailored surgical approach based on evidence.
Q2
Oncology Frontier: Systemic therapy is playing an increasingly important role in early bladder cancer, particularly in organ-preserving strategies. What is your experience in this area?
Professor Yiping Zhu: Bladder preservation has become a major research focus in the past five to six years. Traditionally, the standard treatment for MIBC—or for patients who relapse after multiple intravesical therapies—has been radical cystectomy with urinary diversion. However, urinary diversion can lead to complications such as infections and stoma-related issues, significantly affecting quality of life.
In recent years, multimodal strategies combining immunotherapy, targeted therapy, and radiotherapy—sometimes in triple or quadruple combinations—have achieved encouraging results in bladder preservation.
With careful patient selection and individualized treatment planning, long-term follow-up has shown that patients can achieve overall survival comparable to radical cystectomy, while preserving bladder function and significantly improving quality of life.
However, strict patient selection is essential. Ideal candidates include patients with T2-stage, solitary tumors, no hydronephrosis, no extensive carcinoma in situ, and good treatment compliance. Only in such patients can bladder-preserving therapy be considered appropriate.
Q3
Oncology Frontier: Could you share key research achievements and clinical features of your team?
Professor Yiping Zhu: Our team has made several advances in surgical techniques, particularly in improving radical cystectomy procedures for female patients.
Traditionally, radical cystectomy in women involves extensive resection, including removal of reproductive organs such as the uterus, ovaries, and anterior vaginal wall. This can lead to significant physical and functional consequences, including urinary incontinence and loss of reproductive function.
Through our research, we found that in most cases, removal of these reproductive organs is unnecessary. Literature review and clinical data indicate that only a small proportion of bladder cancers invade female reproductive organs—approximately 90% to 95% of patients have no such involvement.
Based on this evidence, we have developed organ-preserving radical cystectomy techniques for female patients. With careful preoperative selection—ensuring that tumors are not located in the trigone or posterior wall, are ≤T3 stage, and show no invasion on multiparametric MRI—this approach is both safe and effective.
Importantly, this technique does not compromise oncologic outcomes while preserving reproductive organ function, leading to a significant improvement in patients’ quality of life.
Expert Profile
Yiping Zhu Fudan University Shanghai Cancer Center
Professor Zhu Yiping specializes in bladder cancer treatment and surgical innovation, with a strong focus on bladder preservation strategies and function-sparing techniques.
