At the beginning of 2026, the Beijing Academic Exchange Conference for Young Physicians in Urologic Oncology was grandly held in Beijing. The meeting focused on frontier advances and standardized practices in urologic oncology and brought together numerous domestic experts and scholars in the field.At the conference, Sujun Han delivered a comprehensive and in-depth interpretation of the 2026 NCCN Clinical Practice Guidelines for Bladder Cancer. From optimized risk stratification in non–muscle-invasive bladder cancer (NMIBC), to restructuring perioperative strategies for muscle-invasive bladder cancer (MIBC), and finally to the disruptive transformation of first-line therapy for advanced urothelial carcinoma, Professor Han’s presentation outlined a grand blueprint for the transition of urothelial cancer management from experience-based medicine to precision medicine and full-lifecycle care.
Based on Professor Han’s on-site presentation at the National Cancer Center / Cancer Hospital, Chinese Academy of Medical Sciences, this article systematically summarizes the key highlights of the guideline update and its clinical implications.
NMIBC: Dual Innovation in Risk Stratification and Drug-Delivery Systems
Professor Han pointed out that the 2025 NCCN Guidelines underwent three iterative updates, with a central objective of further improving diagnostic and therapeutic precision and individualization. This trend is particularly evident in the management of non–muscle-invasive bladder cancer (NMIBC).
First, the updated guidelines place higher demands on pathological diagnostic accuracy. In terminology, TIS and CIS have been standardized and unified under the term carcinoma in situ (CIS), simplifying clinical communication. More importantly, the risk stratification system has been refined: aggressive histologic variants—such as micropapillary, plasmacytoid, and sarcomatoid subtypes—are now explicitly categorized as very high-risk features.
Professor Han emphasized that once these high-risk factors are identified, clinicians should adopt more aggressive treatment strategies and intensified surveillance to prevent disease progression caused by undertreatment.
From a therapeutic standpoint, bladder-preserving strategies have been further strengthened, and the surgical indications for radical cystectomy in NMIBC have been further narrowed. For BCG-unresponsive high-risk NMIBC, the guidelines now incorporate several randomized controlled trial (RCT)–validated alternatives, offering new hope for patients seeking bladder preservation.
Among these, non-replicating adenoviral vector–based gene therapy has been recommended due to favorable efficacy. In addition, an immunotherapy combination of an interleukin-15 (IL-15) superagonist plus BCG has been approved and incorporated into the guidelines. Notably, the recommendation level for pembrolizumab has been upgraded, now listed as a Category 1 option for patients who are BCG-intolerant and who refuse or are unfit for surgery.
Another major highlight of this update is the introduction of novel drug-delivery systems. Professor Han specifically highlighted TAR-200, a sustained-release intravesical gemcitabine delivery system. Based on clinical data, TAR-200 achieved a complete response (CR) rate of 82.4% in BCG-unresponsive patients, with a median duration of response exceeding two years. It received FDA approval in September 2025 and has since been incorporated into the NCCN Guidelines.
Meanwhile, the approval of subcutaneous pembrolizumab not only confirmed its non-inferiority compared with intravenous formulations, but also significantly improved treatment convenience and efficiency through the use of hyaluronidase-enabled delivery, enhancing both clinical workflow and patient experience.
MIBC: Reshaping Perioperative Strategies and Refining Bladder Preservation
With regard to muscle-invasive bladder cancer (MIBC), Professor Han emphasized that enrichment of perioperative treatment options and refinement of bladder-preserving strategies constitute the core updates in the 2026 guidelines.
While radical cystectomy remains a cornerstone of therapy, bladder preservation has become an irreversible trend. The guidelines have now provided stricter selection criteria for patients eligible for trimodality therapy (TMT) and have assigned it a Category 1 recommendation. Indications for partial cystectomy have also been further expanded.
In perioperative systemic therapy, chemotherapy is no longer the sole “standard answer.” The introduction of immunotherapy and antibody–drug conjugates (ADCs) has fundamentally altered the treatment landscape. For cisplatin-eligible patients, cisplatin-based neoadjuvant chemotherapy (e.g., gemcitabine + cisplatin) remains a Category 1 recommendation. However, for cisplatin-eligible patients seeking more effective regimens, the guidelines now include a “sandwich” strategy combining immunotherapy with chemotherapy, specifically durvalumab plus gemcitabine/cisplatin, offering a new clinical option.
The most transformative advance has occurred in cisplatin-ineligible patients. Professor Han provided an in-depth interpretation of the paradigm shift driven by the EV-303 trial: the platinum-free sandwich regimen of enfortumab vedotin plus pembrolizumab (EV+P) has been incorporated into perioperative treatment recommendations. This regimen demonstrated superior event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) rates compared with radical surgery alone, with an acceptable safety profile—effectively filling the long-standing therapeutic gap for cisplatin-ineligible patients.
In the adjuvant setting, in addition to previously recommended nivolumab, the guidelines have now added pembrolizumab as an adjuvant option. Professor Han further noted that adjuvant treatment selection should align with the neoadjuvant regimen used:
- If immunotherapy + GC was used preoperatively, postoperative immunotherapy maintenance is recommended;
- If ADC + immunotherapy was used preoperatively, continuation of EV+P maintenance is advised postoperatively—thus forming a closed-loop, full-course management strategy.
Advanced Urothelial Carcinoma: EV+P Establishes a New First-Line Standard and Elevates Biomarkers
In discussing updates for metastatic urothelial carcinoma, Professor Han described the shift in first-line therapy as nothing short of a revolution. With the landmark results of the EV-302 trial, the guidelines have eliminated previous stratification based on cisplatin eligibility and established a unified first-line standard: EV+P.
Professor Han explained that EV-302 demonstrated doubling of both progression-free survival (PFS) and overall survival (OS) compared with traditional gemcitabine/cisplatin chemotherapy, with even greater benefit observed in Asian populations. These findings officially usher in the era of immunotherapy plus ADCs for first-line treatment of advanced disease.
At the same time, Professor Han objectively noted that for certain special populations—such as patients with severe peripheral neuropathy, serious dermatologic toxicity, uncontrolled hyperglycemia, or limited financial resources—alternative regimens must still be considered, reflecting the guideline’s balance between universal standards and individualized care.
For second-line and later-line therapy, the guidelines emphasize prior treatment history and molecular testing as dual guiding principles. Professor Han stressed that biomarker-driven precision therapy has been substantially elevated. The role of pathology in multidisciplinary teams (MDT) continues to expand, and testing for PD-L1, FGFR, and HER2 has become a prerequisite for selecting subsequent treatment strategies. In addition, circulating tumor DNA (ctDNA) monitoring has been incorporated into follow-up for advanced urothelial carcinoma, further supporting precision decision-making.
Future Outlook
In his concluding remarks, Professor Han offered a forward-looking vision for the future of urothelial cancer management, highlighting three major paradigm shifts:
- From radical resection to individualized, organ-preserving multimodal therapy, maximizing quality of life without compromising efficacy;
- From chemotherapy-dominant strategies to diversified precision combinations, including immunotherapy, ADCs, targeted agents, gene therapy, and device-based platforms such as TAR-200;
- From experience-based treatment to biomarker-guided precision pathways, moving away from “one-size-fits-all” approaches toward molecularly informed care.
Professor Han concluded that with the widespread application of breakthrough regimens such as EV+P in perioperative and first-line advanced settings, together with the clinical implementation of novel drug-delivery technologies, patients with urothelial carcinoma—especially those who are platinum-ineligible—will gain increasingly diverse and effective survival options.
Conclusion
The 2026 NCCN Guidelines represent not merely a summary of recent clinical research, but a strategic roadmap for future practice. From molecular subtyping at the micro level to restructuring treatment paradigms at the macro level, urothelial carcinoma management is advancing toward unprecedented precision and efficiency.
These updates provide robust evidence-based support for Chinese clinicians and promise tangible survival benefits for patients—transforming aspiration into measurable outcomes.
Professor Sujun Han
