Editor’s Note: With the continuous emergence of novel therapies and landmark clinical evidence, the treatment landscape of urothelial carcinoma is undergoing profound transformation. Ahead of the 2026 Chinese Society of Clinical Oncology (CSCO) Guidelines Conference, Oncology Frontier – UroStream presents a special series of expert previews on major genitourinary oncology guidelines. In this issue, Professor Cuijian Zhang from Peking University First Hospital, Secretary of the CSCO Urothelial Carcinoma Expert Committee, discusses the evolution of the CSCO urothelial carcinoma guidelines, highlights potential updates in the upcoming edition, and shares insights into the clinical significance of emerging evidence and future directions in the field. His perspectives offer clinicians an early look at evolving treatment paradigms aimed at improving outcomes for Chinese patients.Anticipated Highlights of the Updated CSCO Urothelial Carcinoma Guidelines
1. Perioperative therapy: ADC-based strategies are challenging the role of chemotherapy and ushering in a new era of systemic treatment.
2. Non–muscle-invasive bladder cancer (NMIBC): New cutting-edge treatment options are expected to be added, with early implementation already underway in special medical pilot zones.
3. Advanced urothelial carcinoma: Chemotherapy may soon lose its place as frontline standard therapy, while ADC plus immunotherapy combinations emerge as the new standard of care.
Rooted in Chinese Clinical Practice: Building Practical and Accessible Guidelines
Oncology Frontier – UroStream:
It has been six years since the first edition of the CSCO urothelial carcinoma guidelines was released. As both a contributor to the guideline development process and a clinical user, could you share your reflections on how the guidelines have evolved over time?
Professor Cuijian Zhang:
Thank you very much for the invitation from Oncology Frontier – UroStream. Updating the guidelines has always been one of the most important responsibilities of the CSCO Urothelial Carcinoma Committee, and we have now completed six editions of revisions.
Over the past six years, we have continuously refined the guidelines based on the latest domestic and international clinical evidence, while consistently adhering to two core principles. First, we fully consider drug accessibility in China, real-world clinical scenarios, and the practicality of implementation in routine care. Second, we ensure that the recommendations closely reflect the disease characteristics and treatment needs of Chinese patients. This is one of the key distinctions between the CSCO guidelines and international guidelines such as those from the EAU, AUA, and ASCO.
Particularly over the last two years, Chinese-developed anticancer therapies have achieved several landmark breakthroughs, and these homegrown evidence-based advances have been rapidly incorporated into the guidelines. As both a guideline contributor and clinician, what stands out most to me is the strong practicality of the CSCO urothelial carcinoma guidelines. The content is highly structured, straightforward, and user-friendly. Clinicians can quickly identify the recommended treatment strategies and evidence levels according to disease stage and clinical setting, making it easy to apply in daily practice.
This accessibility, close alignment with Chinese clinical realities, and strong emphasis on domestic innovation and evidence have become the defining characteristics of the CSCO urothelial carcinoma guidelines throughout the past six years.
Upcoming Guideline Updates: ADCs Set to Redefine Perioperative and Advanced Disease Management
Oncology Frontier – UroStream:
The updated CSCO urothelial carcinoma guidelines will soon be released. Could you introduce some of the major anticipated changes?
Professor Cuijian Zhang:
This is undoubtedly the topic clinicians are most eager to hear about. The driving force behind every guideline update is the emergence of new high-level evidence. This year’s major revisions will focus primarily on three key areas: perioperative therapy, non–muscle-invasive bladder cancer (NMIBC), and advanced urothelial carcinoma. At the center of these changes is the growing role of novel therapies, particularly antibody-drug conjugates (ADCs), which are reshaping the treatment landscape.
- 1. Perioperative Therapy: ADCs Challenge Chemotherapy and Open a New Era of Systemic Treatment
Some of the most practice-changing evidence in this update comes from breakthroughs in perioperative and advanced disease treatment. Major studies—including the RC48-C017 trial of the HER2-targeted ADC disitamab vedotin (RC48), as well as the KEYNOTE series and the EV-303 and EV-304 trials evaluating enfortumab vedotin (EV)—have fundamentally changed the perioperative treatment paradigm.
As a result, perioperative management is no longer limited to the traditional concept of neoadjuvant therapy. Instead, the focus has shifted toward a comprehensive systemic treatment strategy centered around surgery and extending across the entire perioperative period.
The most significant change is that ADC-based regimens are increasingly replacing conventional chemotherapy as the cornerstone of perioperative treatment. Both the domestic RC48 studies and the EV plus pembrolizumab trials have demonstrated efficacy that clearly surpasses historical standards.
This means that surgery for muscle-invasive bladder cancer (MIBC) can no longer be considered in isolation from systemic perioperative therapy. Urothelial carcinoma treatment has officially entered a new era.
Historically, gemcitabine plus cisplatin (GC) chemotherapy was essentially the only standard neoadjuvant option. Today, we have far more effective and flexible alternatives. Regardless of renal function or cisplatin eligibility, ADC-centered strategies are becoming mainstream options for both neoadjuvant and adjuvant treatment.
- 2. NMIBC: New Therapeutic Options and Early Access Through Medical Pilot Zones
The updated guidelines are also expected to revise recommendation levels for several novel treatment approaches in NMIBC.
Although therapies such as TAR-200 and N-803 have not yet been broadly approved nationwide in China, they are already accessible through the Boao Lecheng International Medical Tourism Pilot Zone in Hainan.
N-803, an IL-15 superagonist complex, has received FDA approval for BCG-unresponsive NMIBC. TAR-200, a sustained-release intravesical gemcitabine delivery system, has shown impressive antitumor activity in high-risk BCG-refractory or relapsed NMIBC.
Accordingly, the updated guidelines are expected to include these emerging therapies, providing additional bladder-preserving treatment options for patients who fail or cannot tolerate BCG therapy.
- 3. Advanced Disease: Chemotherapy Moves Out of the Frontline as ADC-Immunotherapy Becomes the New Standard
In advanced urothelial carcinoma, perhaps the most dramatic shift is the transition away from chemotherapy as the frontline standard.
For HER2-positive disease, disitamab vedotin plus toripalimab—supported by the positive RC48-C016 trial—has emerged as a frontline recommendation. The study demonstrated a median overall survival (OS) of 31.5 months and a median progression-free survival (PFS) of 13.1 months, substantially outperforming traditional chemotherapy.
Meanwhile, for biomarker-unselected patients, enfortumab vedotin plus pembrolizumab has already replaced chemotherapy as the preferred first-line treatment option. Both regimens are expected to receive major recommendation upgrades in the new guidelines.
Future Directions: Bladder Preservation and Precision Medicine Take Center Stage
Oncology Frontier – UroStream:
Looking ahead, what emerging advances do you believe will most significantly influence clinical practice in urothelial carcinoma?
Professor Cuijian Zhang:
Several important studies are currently underway, and future progress will likely focus on several major directions.
First, bladder-preserving therapy will become one of the field’s most important areas of exploration. Radical cystectomy remains the standard treatment for MIBC and unresectable high-risk NMIBC, but as patients increasingly prioritize quality of life, interest in organ-preserving approaches continues to grow.
Currently, phase II studies evaluating ADCs combined with radiotherapy in HER2-positive NMIBC are progressing smoothly and have already shown highly encouraging efficacy. These studies may eventually establish entirely new evidence-based approaches to bladder preservation.
Second, the development of novel therapies will continue accelerating. Clinical trials investigating HER3- and FGFR-targeted agents, bispecific antibodies, and next-generation ADCs are rapidly expanding across perioperative, adjuvant, metastatic, and NMIBC settings.
Third, treatment decision-making will increasingly shift from stage-based approaches toward biomarker-driven precision medicine. In the future, therapy selection will rely not only on disease stage and treatment history, but also on molecular characteristics such as HER2 expression, Nectin-4 expression, and additional emerging biomarkers. This transition toward molecularly guided individualized treatment will further improve patient survival and quality of life.
Overall, urothelial carcinoma is a field evolving at remarkable speed. We fully expect more landmark breakthroughs to emerge in the coming years, further reshaping clinical practice and bringing new hope to patients worldwide.
Professor Cuijian Zhang
