Editor’s note: Upper tract urothelial carcinoma (UTUC) accounts for about 17.9% of all urothelial carcinomas (UC) in China. For high-risk UTUC, radical nephroureterectomy (RNU) is the standard surgical procedure, but it may lead to loss of kidney function and severely impact long-term quality of life. Kidney preservation has become an increasingly important need among patients with urologic malignancies. As an alternative to RNU, kidney-sparing treatment requires achieving oncologic control while protecting renal function—a major area of ongoing clinical exploration in China. A recent prospective pilot study conducted by Professor Yige Bao’s team at West China Hospital, Sichuan University, published in European Urology Oncology, provides preliminary evidence that HER2-ADC vidicitamab plus a PD-1 inhibitor combined with endoscopic thulium laser ablation may become a novel kidney-sparing option for high-risk UTUC. During the 9th West China Uro-Oncology Tianfu Conference and the 11th Academic Annual Meeting on Urogenital Tumors of the Sichuan Anti-Cancer Association, UroStream invited Professor Bao to interpret the findings and discuss the future potential of HER2 ADC in kidney-sparing strategies for UTUC.
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UroStream
Kidney preservation is an expanding need among UTUC patients. Based on your clinical experience and updates in the European Association of Urology (EAU) guidelines, how should we select suitable candidates for kidney-sparing treatment? Can localized high-risk UTUC be managed with kidney preservation? How should we understand the value of systemic therapy within kidney-sparing strategies?
Professor Yige Bao: Over recent years, UTUC treatment standards have been evolving significantly. Traditionally, RNU was regarded as the only standard treatment for UTUC, especially for high-risk disease. However, emerging evidence shows that kidney-sparing treatment can be safe and effective in selected low-risk UTUC. Low-risk criteria include a solitary tumor, tumor diameter <2 cm, absence of hydronephrosis, negative urine cytology, low-grade biopsy, and no radiologic signs of invasion. The 2025 EAU guidelines no longer recommend RNU for low-risk UTUC and instead recommend kidney-sparing therapy. For a subset of strictly selected high-risk UTUC patients, kidney-sparing treatment may also be considered, although careful evaluation of oncologic control versus renal preservation is required. For high-risk UTUC patients who truly need to preserve the kidney, systemic therapy may help reduce recurrence and prevent progression or metastasis, but this field remains exploratory.
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UroStream
Your team recently published a prospective pilot study in European Urology Oncology investigating perioperative vidicitamab plus a PD-1 inhibitor combined with endoscopic thulium laser ablation as a kidney-sparing approach for high-risk UTUC. Please introduce the study design, the reported efficacy and safety results, renal function outcomes, and how you interpret the clinical significance of this work.
Professor Yige Bao: We are pleased that this study was accepted by European Urology Oncology. The study included 33 patients with localized UTUC treated between June 2021 and February 2024. All patients were classified as high-risk according to EAU criteria; 24 had absolute indications for kidney preservation and 9 had relative indications. Absolute indications included solitary kidney (n=5), bilateral UTUC (n=3), extremely high risk of contralateral recurrence (due to aristolochic acid exposure, Lynch syndrome, etc.; n=8), and impending or existing renal insufficiency (n=8). Relative indications included strong patient preference for kidney preservation (n=7) or severe comorbidities making radical surgery unsuitable (n=2).
All patients received ureteral stent placement 2–4 weeks prior to ureteroscopic biopsy. Complete tumor ablation was achieved in 27 patients—16 after the first ureteroscopic thulium laser procedure and 11 after a second procedure. Six patients could not achieve complete ablation due to lower-pole calyx location (n=3), large tumor volume (n=2), or limited response to systemic therapy (n=1). After biopsy, patients received 2–4 weeks of systemic therapy with vidicitamab plus a PD-1 inhibitor. All patients also received immediate postoperative intravesical instillation (epirubicin 58%, gemcitabine 42%).
Among patients who were alive and did not require salvage RNU, the median follow-up was 23 months (IQR 18–29). Nineteen local recurrences occurred in 12 patients, with 92% occurring within the first year. The 1-year local recurrence-free survival (LRFS) was 67% (95% CI 48–82%), and 2-year LRFS was 64% (95% CI 45–80%). As of February 1, 2025, two patients underwent salvage RNU, with a 2-year conversion-free survival (CFS) of 94% (95% CI 80–99%). Two patients died from non-oncologic causes; 2-year overall survival (OS) and cancer-specific survival (CSS) were 94% (95% CI 80–99%) and 100%, respectively. Four patients developed intravesical recurrence (IVR); IVR-free survival was 97% at 1 year and 88% at 2 years. No patients had distant metastasis or disease progression.
Renal function preservation was the major highlight: mean eGFR improved over 12 months. Although 6 patients (18%) developed transient renal impairment, four (12%) recovered to near baseline by 6 months, and the remaining two (6%) demonstrated sustained improvement beyond baseline values. No significant ureteral strictures occurred. Some patients developed progressive hydronephrosis after stent removal but were successfully managed with temporary stent placement. Stent dependence decreased over time: 21% at 6 months and 12% at 12 months.
Systemic therapy with vidicitamab + a PD-1 inhibitor was well tolerated. The main treatment-related adverse events were peripheral sensory neuropathy (54%) and rash (50%); no grade ≥3 TRAEs occurred. Three patients (9%) developed postoperative UTIs; one febrile case required IV antibiotics.
West China Hospital is among the earliest centers in China to implement kidney-sparing treatment for high-risk localized UTUC and currently has the country’s largest and longest-followed cohort (over 100 high-risk patients followed for nearly five years). This study represents the first published clinical research combining systemic and local therapy for kidney-sparing management of high-risk UTUC. We hope these findings will inform future studies in this area.
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UroStream
This study is the first to integrate systemic therapy with endoscopic laser ablation for kidney-sparing UTUC. Compared with kidney-sparing approaches without systemic therapy, what roles do vidicitamab and immune checkpoint inhibitors (ICI) play in tumor control?
Professor Yige Bao: One of the major challenges in kidney-sparing treatment for localized high-risk UTUC is the elevated risk of recurrence, progression, or metastasis—especially in high-risk strong-criteria patients with high-grade tumors or radiologic evidence of invasion. For patients who meet absolute indications for kidney preservation, such as solitary kidney or bilateral UTUC, we considered combining systemic therapy to reduce these risks.
In another ongoing trial at our center using vidicitamab plus the PD-1 inhibitor tislelizumab as neoadjuvant therapy, the preliminary pathologic complete response (pCR) rate reached 21.43% and the objective response rate (ORR) 78.57%. These impressive outcomes gave us strong confidence in combining vidicitamab + ICI with local therapy in high-risk UTUC.
In our five-year clinical experience, compared with patients who did not receive systemic therapy, combining vidicitamab + ICI reduced local recurrence risk by 54%, bladder recurrence risk by 84%, and nephrectomy risk by 28%. With manageable toxicity, many elderly UTUC patients can tolerate therapy. In this study, the 2-year kidney-preservation rate reached 94%. Vidicitamab and ICIs clearly play a key role.
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UroStream
Based on your experience, how should kidney-sparing UTUC patients be followed? What biomarkers may help predict local recurrence?
Professor Yige Bao: Regular follow-up is essential, especially for high-risk UTUC. Surveillance should include imaging, endoscopy, and urine-based tumor assessment. Endoscopic surveillance and timely consolidation or salvage procedures are crucial. International data and our center’s experience show that patients adhering to scheduled endoscopic follow-up had 22% more recurrences detected and an 87% reduction in nephrectomy risk.
After laser ablation, we recommend a second ureteroscopic evaluation at 6–8 weeks, similar to the “second-look TURBT” concept in bladder cancer. For the first two years, ureteroscopy every 3 months; then every 6 months until year 5; and annually thereafter.
HER2 expression is the strongest predictor of recurrence and also the best predictor of response to vidicitamab. All UTUC patients should undergo HER2 testing to determine suitability for vidicitamab + ICI therapy. Emerging biomarkers such as ctDNA and utDNA may offer additional predictive value in the future.
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UroStream
How might UTUC risk stratification be further optimized? What are future exploration directions for kidney-sparing therapy?
Professor Yige Bao: Current UTUC stratification includes low-risk, high-risk weak, and high-risk strong categories, guiding assessments of muscle invasion and kidney-sparing eligibility. I believe refinement is needed. Future models may include: low-risk suitable for kidney preservation; intermediate-risk where kidney preservation is possible but technically challenging; high-risk requiring combination systemic therapy; and extremely high-risk where kidney preservation carries unacceptable risk and RNU should be prioritized. Integrating systemic therapy response into risk assessment will be an important step.
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UroStream
Your team has made significant contributions to UTUC systemic therapy. Could you share updates from West China Hospital’s vidicitamab-based UTUC research program?
Professor Yige Bao: Our research on HER2 as a UTUC biomarker and vidicitamab as systemic therapy has produced multiple findings. A 2023 systematic review showed HER2 positivity correlates with higher tumor stage, grade, nodal metastasis, and a trend toward poorer recurrence-free survival. A 2024 single-center study of 155 UTUC patients found HER2 expression in 67.1% and overexpression in 35.5%, strongly associated with high-grade pathology and luminal molecular subtype, and that tumor subtype may change upon recurrence.
We also observed that HER2 expression may change after recurrence or metastasis. At ASCO-GU 2025, we reported discordance in HER2 expression between primary UTUC and bladder recurrence or distant metastases, suggesting heterogeneity in response to systemic therapy. At our center, we are conducting the WUTSUP-02 neoadjuvant study using vidicitamab + tislelizumab and the WUTSUP-03 kidney-sparing study based on the present pilot data. More results are expected soon.
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UroStream
UTUC diagnosis faces challenges such as underestimation of staging preoperatively and technical difficulty of ureteroscopic biopsy. Could you share your experience with biopsy technique and developing individualized treatment strategies?
Professor Yige Bao: Ureteroscopic biopsy is “easy to say but hard to do.” Many centers struggle with adequate sampling. At our center, due to high procedural volume, our success rate is quite high—only a few cases each year fail to yield diagnostic tissue.
First, we routinely place a ureteral stent before biopsy. Because inpatient scheduling may involve waiting periods, we place the stent early so the ureter is adequately dilated by the time of surgery. Second, in addition to standard small biopsy forceps, we use extended large forceps or retrieval baskets to obtain larger samples. Bleeding is managed by controlling renal pelvic pressure, adjusting irrigation strength, and using laser coagulation. Biopsy quality is determined by many small technical details, and because biopsy quality directly impacts UTUC treatment quality, we must execute every step meticulously from the beginning.
Professor Yige Bao
