Editor's Note: Although radical cystectomy remains the standard treatment for muscle-invasive bladder cancer (MIBC) and high-risk non-muscle-invasive bladder cancer (NMIBC) that is unresponsive to Bacillus Calmette-Guérin (BCG) therapy, many patients are either unsuitable for or unwilling to undergo radical cystectomy because of underlying comorbidities and the potential impact on quality of life. Consequently, there is an urgent need to explore novel treatment approaches. At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, a study conducted by the team of Professor Wang He and Professor Wenlong Zhong from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, was selected for presentation. The study evaluated a bladder-preservation strategy combining disitamab vedotin-based systemic targeted immunotherapy with transurethral resection of bladder tumor (TURBT) and pelvic lymph node dissection (PLND), offering a new possibility for bladder preservation in patients with MIBC. Oncology Frontier – UroStream invited both experts to discuss the clinical value, efficacy, and future prospects of this innovative approach.Oncology Frontier – UroStream
TURBT is a cornerstone surgical procedure in bladder cancer management. Its technical execution and optimization are critical for reducing postoperative recurrence risk and improving diagnostic accuracy. Could you share your experience with TURBT and its clinical value?
Professor Wang He:
In clinical practice, bladder cancer is generally classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) based on whether the tumor invades the bladder muscle layer. TURBT plays an important role in the management of both disease categories, although the objectives and technical considerations differ significantly.
For NMIBC, the primary goals are complete tumor resection, accurate pathological diagnosis, and minimization of recurrence risk. The resection should encompass the tumor itself, the tumor base, and the surrounding mucosa, typically extending at least 1 cm beyond the visible lesion until normal-appearing mucosa is reached. Following resection, the surgical margins should be sampled separately for pathological examination to ensure the absence of residual tumor. The depth of resection should include the muscularis propria, and pathological assessment must confirm the presence of smooth muscle tissue to ensure procedural adequacy.
Importantly, NMIBC often exhibits multifocal disease, necessitating a meticulous and comprehensive examination of the entire bladder. Surgeons should systematically inspect the trigone, lateral walls, posterior wall, dome, and other anatomical regions, excising any suspicious lesions and obtaining separate biopsies from suspicious mucosal areas. Particular attention should be paid to carcinoma in situ (CIS), which often manifests as velvety mucosal changes or erythematous lesions. Such abnormalities must be biopsied or resected separately to avoid missed diagnoses.
For MIBC, TURBT alone is generally insufficient for curative treatment. In this setting, the procedure primarily serves a diagnostic purpose or facilitates maximal tumor debulking as part of a bladder-preservation strategy. During surgery, careful control of bladder distension is essential to minimize the risk of bladder perforation. At the conclusion of the procedure, complete evacuation of bladder fluid is recommended, and hemostasis should be achieved under decompressed conditions to reduce the risk of postoperative bleeding.
Following TURBT, patients with MIBC typically require multimodal treatment incorporating radiotherapy, chemotherapy, immunotherapy, and targeted therapy to improve outcomes. Notably, a substantial proportion of MIBC tumors exhibit HER2 overexpression, which appears to be associated with earlier recurrence, higher tumor grade, and poorer prognosis. Consequently, there is a strong rationale for developing HER2-directed precision treatment strategies in this patient population.
Oncology Frontier – UroStream
Your team investigated a comprehensive treatment strategy combining disitamab vedotin-based systemic therapy with PLND-based local treatment in place of radiotherapy. The regimen enabled pathological complete responses in the majority of patients, laying the groundwork for bladder preservation. Could you elaborate on the key strengths of this approach and the clinical benefits observed? How might this novel treatment model influence future bladder-preservation strategies?
Professor Wenlong Zhong:
Building upon targeted immunotherapy centered on disitamab vedotin, our team introduced innovations in both systemic and local treatment, creating a new pathway for bladder preservation in patients with bladder cancer.
From a systemic treatment perspective, we developed an innovative “targeted therapy plus immunotherapy” sandwich strategy. Specifically, patients receive six cycles of neoadjuvant disitamab vedotin combined with immunotherapy, followed by TURBT and PLND. Patients who achieve a clinical complete response (cCR) subsequently receive an additional six cycles of consolidation targeted immunotherapy.
This prolonged and sustained synergistic approach enables deeper eradication of microscopic residual disease, substantially improving the likelihood of successful bladder preservation while maintaining bladder function.
On the local treatment side, we departed from the traditional framework by replacing radiotherapy with surgical lymph node dissection. This strategy offers several advantages. First, surgical dissection can remove occult micrometastatic lesions that may be undetectable on imaging. Second, direct pathological assessment of surgically obtained specimens provides more accurate staging than imaging alone, thereby supporting more informed treatment decisions. In addition, avoiding radiotherapy reduces treatment-related toxicities while maintaining therapeutic efficacy.
As of May 2026, 31 patients had been enrolled in the study, and 17 had undergone efficacy evaluation. Remarkably, 82.35% achieved a clinical complete response. Among the 13 patients who underwent TURBT combined with PLND, 92.3% demonstrated both negative bladder pathology and negative lymph node pathology.
One particularly noteworthy case involved a patient with no residual tumor in the bladder but persistent lymph node metastasis; following treatment, the patient ultimately achieved a pathological complete response (pCR), underscoring the unique value of surgical lymph node dissection.
In terms of safety, the most common adverse events were pruritus and sensory abnormalities, all of which were grade 1 or 2 and manageable with appropriate supportive care. Overall, the data indicate that this treatment model delivers impressive efficacy while maintaining a favorable safety profile, providing a strong foundation for future clinical application.
The study also offers important insights into bladder-preservation strategies. First, it supports an efficacy-driven, adaptive treatment approach. Not all patients seeking bladder preservation should automatically retain their bladder. Instead, treatment decisions should be guided by response. Patients who achieve cCR after neoadjuvant therapy may proceed with bladder-preservation protocols, whereas those with suboptimal responses should be promptly considered for radical surgery to maximize treatment outcomes.
Second, this approach highlights the complementary roles of systemic therapy and surgery in the era of precision medicine. Rather than relying on a one-size-fits-all strategy or attempting to replace surgery entirely with drug therapy, the integration of both modalities allows each to contribute its strengths, maximizing patient benefit and advancing individualized bladder cancer care.
Oncology Frontier – UroStream
China has independently developed innovative therapies such as HER2-targeting ADCs, which have been featured prominently at international conferences such as ASCO and have even influenced clinical guidelines. As an expert in genitourinary oncology, how do you view the growing global impact of Chinese-developed targeted immunotherapy combinations in urothelial carcinoma?
Professor Wang He:
China has made remarkable progress in the development of innovative therapies in recent years, with major advances in targeted therapy, immunotherapy, and particularly antibody-drug conjugates (ADCs). Numerous ADC candidates are currently under development in China, including both single-target and dual-epitope ADCs, several of which have already entered clinical trials.
Among them, disitamab vedotin, which targets HER2, has demonstrated particularly impressive clinical performance. It has been approved in China and has secured indications for both first-line and second-line treatment of advanced urothelial carcinoma, providing clinicians with a powerful therapeutic option.
In the first-line treatment setting for advanced urothelial carcinoma, disitamab vedotin-based combinations have delivered remarkable efficacy, nearly doubling overall survival compared with traditional chemotherapy while demonstrating substantially lower toxicity. This represents a significant step toward achieving highly effective, low-toxicity treatment.
Mechanistically, ADCs such as disitamab vedotin are often described as “molecular missiles.” By using antibodies to precisely recognize tumor-specific antigens such as HER2, they selectively deliver potent cytotoxic agents to cancer cells, maximizing antitumor activity while minimizing off-target toxicity and improving the patient experience.
Given their strong performance in advanced urothelial carcinoma, HER2-targeting ADCs are now being actively explored in earlier disease settings, including neoadjuvant treatment and bladder-preservation strategies. Preoperative precision therapy can reduce tumor burden, control occult metastatic disease, and create more favorable conditions for subsequent surgery, thereby improving overall treatment outcomes.
Several bladder-preservation studies, including those conducted by our team, have already shown encouraging results in patients with HER2-overexpressing tumors (IHC 2+/3+). Many patients have successfully preserved their bladder, leading to meaningful improvements in quality of life.
Nevertheless, it is important to recognize that every patient’s disease is unique. While HER2-targeted ADCs offer new hope for bladder preservation, treatment decisions should always be based on comprehensive evaluation by experienced clinicians to ensure the most appropriate personalized treatment strategy and the best possible outcomes.
Oncology Frontier – UroStream
This treatment strategy currently targets patients with cT2–4aN0M0 disease and HER2 IHC 2+/3+ expression. Looking ahead, what additional opportunities do you see for disitamab vedotin-based approaches in urothelial carcinoma?
Professor Wenlong Zhong:
This study adopted a relatively conservative enrollment strategy, focusing on patients with HER2 IHC 2+/3+ expression. However, large clinical trials and real-world clinical experience have already demonstrated that patients with HER2 IHC 1+ expression and above can also benefit from disitamab vedotin-based treatment in the first-line advanced setting. These findings suggest that the therapeutic benefits of disitamab vedotin may extend across a broader HER2-expressing population.
Accordingly, future research will expand eligibility to include patients with low HER2 expression.
At the same time, treatment is moving progressively earlier in the disease course. Our team has already expanded research into high-risk NMIBC, investigating a combination of BCG and disitamab vedotin with the goal of bringing precision therapy to more patients with earlier-stage disease. Preliminary findings have been highly encouraging, and the relevant clinical studies are advancing steadily.
From a precision medicine perspective, we are also developing a molecular classification system for HER2-positive patients. Through detailed molecular characterization, we aim to identify individuals most likely to benefit from therapy while exploring additional combination strategies for those with less favorable responses.
We have recently initiated a biomarker-driven clinical study in which one cohort receives disitamab vedotin plus toripalimab, while another cohort receives additional therapies on top of this backbone regimen. The goal is to provide increasingly individualized neoadjuvant treatment options and ultimately improve patient outcomes.
We have also established a multidimensional, dynamic monitoring framework for patients undergoing bladder-preservation therapy. Conventional surveillance methods include MRI, TURBT, and urine cytology, allowing assessment of both intravesical and extravesical disease.
In addition, we have incorporated advanced technologies such as circulating tumor DNA (ctDNA), urinary tumor DNA (utDNA), and a proprietary urine methylation assay to facilitate earlier detection of recurrence risk. Once signs of recurrence are identified, intensified treatment can be rapidly implemented through systemic therapy, surgical intervention, or a combination of approaches to prevent disease progression.
Furthermore, we continue to explore the integration of metabolomic markers and DNA methylation biomarkers into our monitoring platform, expanding surveillance beyond traditional approaches and strengthening the safety framework supporting bladder-preservation treatment.
About the Experts
Professor Wang He
Professor Wenlong Zhong
