Editor’s Note: With ongoing advances in research, combinations of targeted therapy and immunotherapy have become the standard first-line treatment for advanced urothelial carcinoma. However, upper tract urothelial carcinoma (UTUC) differs significantly from bladder cancer in terms of anatomical structure, pathological characteristics, prognosis, and recurrence risk. As a result, radical nephroureterectomy (RNU) remains the gold standard for non-metastatic UTUC. Nevertheless, effective postoperative adjuvant treatment options remain limited, and outcomes are suboptimal, highlighting an urgent need for improvement. At the 2026 European Association of Urology Congress (EAU26), Professor Liang-You Gu from the Chinese PLA General Hospital presented a phase II study evaluating disitamab vedotin combined with tislelizumab as adjuvant therapy for UTUC. The study attracted considerable attention and offers a promising new therapeutic option for patients with high-risk UTUC.
Following the conference, Oncology Frontier – UroStream invited Professor Liang-You Gu to discuss the current challenges in UTUC management, recent research advances, and the clinical value of disitamab vedotin–based combination strategies.
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Question: Patients with UTUC are prone to recurrence after radical surgery, with 5-year disease-free survival (DFS) rates of only 35%–50% in locally advanced disease. Given the lack of effective adjuvant therapies, what are the current challenges in postoperative management?
Professor Liang-You Gu: Upper tract urothelial carcinoma (UTUC), which includes renal pelvic and ureteral cancers, belongs to the spectrum of urothelial carcinoma alongside bladder cancer. However, it differs significantly in clinical characteristics, treatment requirements, and prognosis.
In China, the clinical management of UTUC remains particularly challenging. First, UTUC accounts for approximately 17.9% of all newly diagnosed urothelial carcinoma cases in China, significantly higher than in Western populations (5%–10%). Moreover, about two-thirds of patients are already diagnosed with muscle-invasive disease, which is associated with poorer outcomes. Clinical data show that the 5-year cancer-specific survival is less than 50% for patients with pT2/pT3 disease and less than 10% for those with pT4 disease.
Second, recurrence rates after radical nephroureterectomy remain high. RNU—comprising removal of the kidney, entire ureter, and a bladder cuff—is the standard treatment for non-metastatic UTUC. However, postoperative bladder recurrence is common. Current guidelines recommend intravesical chemotherapy or systemic chemotherapy after surgery to reduce recurrence risk.
Third, a high proportion of UTUC patients have chronic kidney disease, and renal function often declines further after surgery. Studies show that 20%–25% of patients are unable to tolerate platinum-based chemotherapy. Although several immunotherapy-based adjuvant strategies have been explored, studies such as CheckMate 274, IMvigor010, and AMBASSADOR have not demonstrated significant DFS benefit in UTUC subgroups.
Taken together, these limitations highlight the urgent need for more effective adjuvant treatment strategies. Given the restricted applicability of platinum-based chemotherapy and the lack of UTUC-specific immunotherapy data, we explored the potential of combining antibody–drug conjugates (ADCs) with immunotherapy in this setting. Disitamab vedotin–based regimens have already shown promising efficacy and safety in advanced urothelial carcinoma, providing the rationale for this approach.
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Question: Your phase II study of disitamab vedotin combined with immunotherapy was presented at EAU26. Could you describe the study design and its preliminary results?
Professor Liang-You Gu: This prospective phase II study enrolled patients with high-risk, non-metastatic, HER2-expressing UTUC.
In the experimental group, patients who were ineligible for or declined platinum-based chemotherapy (HER2 IHC 1+/2+/3+) received six cycles of disitamab vedotin combined with tislelizumab during the induction phase, followed by eleven cycles of tislelizumab maintenance therapy.
In the control group, patients eligible for platinum-based chemotherapy (HER2 IHC 0–3+) received gemcitabine combined with cisplatin or carboplatin for four cycles.
The primary endpoint was disease-free survival (DFS), while secondary endpoints included overall survival (OS) and safety.
A total of 84 patients were enrolled: 50 in the combination group and 34 in the chemotherapy group. Baseline characteristics were comparable between the two groups.
As of February 4, 2026, the median follow-up was 10.8 months in the combination group and 22.3 months in the chemotherapy group. During follow-up, only one patient in the combination group experienced recurrence or metastasis, compared with eight patients in the control group. Median DFS had not yet been reached in either group.
The 12-month DFS rate was 97.4% (95% CI: 95.0%–99.7%) in the combination group, compared with 82.4% (95% CI: 76.2%–88.6%) in the chemotherapy group.
In terms of safety, treatment-related adverse events occurred in 92% of patients in the combination group and 97.1% in the chemotherapy group. No treatment-related deaths were observed.
Overall, disitamab vedotin combined with tislelizumab demonstrated strong antitumor activity with a significantly improved DFS rate and a more favorable safety profile compared with chemotherapy, offering a more effective and tolerable treatment option for patients.
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Question: Recent ASCO GU and EAU studies have highlighted the importance of biomarkers in urothelial carcinoma. How can biomarkers be better utilized in clinical practice to benefit more UTUC patients?
Professor Liang-You Gu: Biomarkers such as HER2 and Nectin-4 have demonstrated significant predictive and prognostic value for ADC-based therapies. The emergence of agents like disitamab vedotin marks a shift toward biomarker-driven precision medicine in urothelial carcinoma.
However, to fully realize the clinical value of biomarkers, further efforts are required.
First, it is essential to standardize and improve the accuracy of HER2 testing. Updated expert consensus guidelines in 2026 recommend routine HER2 testing in patients with intermediate- to high-risk NMIBC, muscle-invasive disease, and advanced urothelial carcinoma. This will help refine prognostic assessment and guide the use of HER2-targeted therapies.
Second, there is a need to expand minimally invasive biomarker monitoring. Traditional imaging and invasive procedures have limitations, whereas circulating biomarkers such as circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) offer convenient, non-invasive tools for disease monitoring.
Recent studies presented at ASCO GU and EAU—including IMvigor011, RETAIN, and NIAGARA—have explored the role of ctDNA in guiding adjuvant therapy. These approaches may shift treatment paradigms from a “one-size-fits-all” model toward precision strategies based on minimal residual disease, enabling dynamic treatment adjustment and improved outcomes.
Overall, biomarkers are becoming indispensable in the comprehensive management of urothelial carcinoma, driving the field toward more precise and less invasive care.
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Question: Based on recent research advances, what are the future applications of disitamab vedotin in UTUC?
Professor Liang-You Gu: Disitamab vedotin–based combinations have already become a standard first-line precision treatment for advanced urothelial carcinoma. With the publication of the RC48-C016 study in The New England Journal of Medicine, it is expected that future guideline updates will further strengthen its recommendation.
Several studies presented at EAU26 have explored its role in UTUC:
- A study from Peking University First Hospital demonstrated that disitamab vedotin combined with radiotherapy improved 1-year DFS (93.3% vs. 72.7% with surveillance), with good tolerability.
- The DISTINCT-I study from Renji Hospital showed that disitamab vedotin plus immunotherapy enabled tumor downstaging and kidney preservation, with a 1-year kidney preservation rate of 70% and improved renal function compared with nephrectomy.
Additionally, our team conducted a real-world study evaluating disitamab vedotin combined with toripalimab as neoadjuvant therapy in muscle-invasive bladder cancer. Preliminary results suggest that this approach may enable bladder preservation in selected patients, with further data to be presented at future conferences.
Looking ahead, we plan to further investigate neoadjuvant applications of disitamab vedotin–based combinations in UTUC to improve both survival outcomes and quality of life.
In summary, HER2-targeted ADCs such as disitamab vedotin play an increasingly important role across the entire treatment continuum of UTUC. From advanced disease to adjuvant and neoadjuvant settings, these therapies offer improved efficacy, better tolerability, and the potential for organ preservation. Ongoing and future studies are expected to further refine and optimize treatment strategies for UTUC.
Professor Liang-You Gu
