Editor’s Note: Upper tract urothelial carcinoma (UTUC), which originates in the renal pelvis or ureter, is a distinct disease entity with unique characteristics in China. Accounting for 17.9% of all urothelial cancers in the country, UTUC represents a disproportionately high disease burden compared to Western countries and warrants greater clinical attention. At the 2025 ASCO Annual Meeting, a study from the Peking University First Hospital team highlighted the promising efficacy and safety of disitamab vedotin in combination with radiotherapy in HER2-overexpressing UTUC patients, offering a new adjuvant treatment strategy. Oncology Frontier – UroStream invited Professor Xuesong Li and Professor Xiaoying Li for a joint discussion with Professor Qi Tang to analyze the unique features and treatment challenges of UTUC in China, the therapeutic value and mechanisms of disitamab vedotin plus radiotherapy, future directions for UTUC research, and the development goals of the CUDA-UTUC collaborative group.Oncology Frontier – UroStream
UTUC has a different pathogenesis compared to bladder cancer, and Chinese UTUC cases differ significantly from those in Western populations. Therefore, Western treatment paradigms cannot be directly applied to Chinese patients. The Department of Urology at Peking University First Hospital has long been focused on UTUC and has gained extensive clinical experience. Based on your practice, could you describe the key characteristics and challenges of UTUC in China?
Professor Xuesong Li: UTUC, or upper tract urothelial carcinoma, encompasses malignancies of the renal pelvis and ureter. Historically, both the general public and the medical community have paid relatively little attention to this cancer, primarily because of its low incidence. In standard urology textbooks, UTUC is often categorized as a “rare disease,” especially in Western populations where it constitutes a small fraction of urothelial cancers. However, the situation in China is quite different—there are notable disparities in etiology, absolute case numbers, incidence rates, diagnostic and treatment practices, and even molecular mechanisms.
From an epidemiological standpoint, China sees a much higher number of UTUC cases and a greater incidence rate compared to Western countries. In Western populations, UTUC typically accounts for only 5%–10% of all urothelial carcinomas. Yet in China, this proportion is significantly higher. A 2018 survey covering 32 major centers across the country reported that UTUC made up an average of 17.9% of all urothelial cancer cases, with individual centers reporting rates ranging from 9.3% to 29.9%.
There are also striking differences in risk factors and patient demographics. In the West, UTUC is more common in men than women. But in China, the trend is reversed—more women are diagnosed with UTUC. Furthermore, the widespread use of traditional Chinese medicine has introduced unique risk factors not seen in the West. For example, aristolochic acid, found in certain Chinese herbal remedies, has been identified as a clear carcinogen associated with UTUC. These etiological differences also influence the disease presentation. Chinese UTUC patients are more likely to have multifocal or bilateral disease and often present with multiple comorbidities, creating a clinical picture that is quite distinct from that of Western patients.
Because of these substantial differences, we cannot simply adopt Western guidelines for Chinese UTUC patients. What we need are China-specific treatment algorithms developed through top-down strategic planning and validated by large-scale clinical experience. This requires Chinese clinicians to pioneer new approaches tailored to the unique characteristics of our patient population.
Clinically speaking, UTUC patients in China tend to present at more advanced stages compared to those with bladder cancer. They also have a higher risk of metastasis. Unfortunately, the standard therapies—including traditional chemotherapy, immunotherapy, and some emerging treatments—have not yet achieved ideal outcomes for UTUC. For instance, in conventional urothelial carcinoma, surgery followed by chemotherapy often yields favorable results, and immunotherapy has significantly improved the treatment of bladder cancer. However, these benefits have not translated effectively to UTUC.
Given these challenges, identifying more effective therapeutic strategies is a pressing need. Our goal is to improve survival while preserving patients’ quality of life. Although there are many hurdles, Chinese physicians remain committed to advancing this field. We have already begun to accumulate valuable clinical experience and have made early progress in generating evidence-based strategies tailored to UTUC.
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As previously mentioned, ADC drugs targeting HER2 have become a focal point in urothelial carcinoma research. As a key biomarker in UC, what is the prognostic and therapeutic significance of HER2 in UTUC? What were the major findings regarding disitamab vedotin in adjuvant UTUC treatment shared at this year’s ASCO meeting? In your view, how might these findings reshape the treatment landscape for UTUC in China?
Professor Qi Tang: It is well known that HER2 plays an important prognostic and clinical role in urothelial carcinoma. In UC, HER2 expression is often associated with a poor prognosis. For example, it is linked to increased risk of progression in non–muscle-invasive bladder cancer (NMIBC), worse treatment outcomes in high-risk NMIBC, and less favorable results in muscle-invasive bladder cancer (MIBC).
One study showed that HER2 overexpression (IHC 2+/3+) was found in as many as 63% of UTUC patients. With the emergence of novel antibody–drug conjugates (ADCs), HER2 has become a promising prognostic and therapeutic target in UTUC. Therefore, HER2 testing can help optimize treatment strategies and maximize clinical benefit.
At the 2025 ASCO Annual Meeting, our center presented new findings from a study evaluating disitamab vedotin combined with radiotherapy as adjuvant treatment for high-risk UTUC (Abstract e16583). This was the first study to assess the efficacy and safety of ADCs in combination with radiotherapy for UTUC in the adjuvant setting. We enrolled patients with HER2-overexpressing UTUC (IHC 2+/3+) who were ineligible for cisplatin. Eligible participants had undergone radical nephroureterectomy and had high-risk pathological features, including pT2N0M0 with high-grade tumors, multifocal disease, or positive surgical margins; pT3-4N0M0; or pTanyN1-2M0. Based on patient preference, individuals were non-randomly assigned in a 1:1 ratio to either the adjuvant treatment group or the observation group.
The treatment group received disitamab vedotin (2.0 mg/kg on Day 1, every two weeks for 6 months) in combination with radiotherapy (45–50 Gy over 25 fractions), with therapy initiated within 90 days post-surgery. The primary endpoint was disease-free survival (DFS), and secondary endpoints included overall survival (OS), metastasis-free survival (MFS), local recurrence-free survival (LRFS), and safety. Exploratory endpoints focused on correlating blood and urine biomarkers with treatment efficacy.
As of December 2024, 31 patients had been enrolled—15 in the adjuvant treatment group and 16 in the observation group. Among them, 10 (66.7%) in the treatment arm and 4 (25%) in the observation arm had HER2 IHC 3+ tumors. To date, 3 patients in the treatment group have completed adjuvant therapy; one patient withdrew due to cardiovascular issues, and the rest are continuing treatment. The median follow-up period is six months. So far, no recurrences have been observed in the treatment group, while five patients in the observation group have experienced disease recurrence.
The most common treatment-related adverse events (TRAEs) included abdominal pain (13.3%), rash (13.3%), leukopenia (13.3%), elevated ALT/AST (13.3%), elevated GGT (6.7%), fatigue (6.7%), and thrombocytopenia (6.7%). Grade ≥3 TRAEs occurred in only one patient (6.7%), indicating good overall tolerability. The only grade 3 adverse event reported was gastrointestinal bleeding in a single patient.
These findings suggest that disitamab vedotin combined with radiotherapy offers a promising new adjuvant strategy for patients with HER2-overexpressing UTUC. The regimen demonstrated encouraging efficacy and an acceptable safety profile, positioning it as a potential new standard that could reshape the adjuvant treatment landscape for UTUC in China.
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Multidisciplinary teams (MDTs) play a vital role in the management of UTUC. In the context of adjuvant therapy following surgery, how can radiotherapy work synergistically with pharmacological treatments to reduce recurrence risk and achieve long-term disease-free survival? What explorations has the Department of Radiation Oncology at Peking University First Hospital conducted in this area, and what preliminary results have been achieved?
Professor Xiaoying Li: UTUC is a relatively rare form of urothelial carcinoma, but its epidemiology and clinical features in Asia—especially in China—are distinct and reflect clear regional characteristics. Currently, adjuvant chemotherapy remains the guideline-recommended approach for UTUC in urothelial cancer management. However, published data show that the 3-year progression-free survival (PFS) rate is only around 71%. From a clinical perspective, this is far from ideal, particularly when compared with outcomes in other malignancies. This suggests there is significant room for improvement in adjuvant treatment strategies for UTUC.
Regrettably, two major trials exploring adjuvant immunotherapy—CheckMate-274 and AMBASSADOR—yielded positive results in bladder cancer, but failed to demonstrate significant benefit in the UTUC subgroups. By thoroughly analyzing these outcomes and leveraging our hospital’s extensive database, we identified a key issue: regional lymph node recurrence—especially in the peritoneal lymph nodes—emerges as a common and early pattern of relapse after surgery in UTUC patients.
As a high-volume center for UTUC surgeries, the Department of Urology at Peking University First Hospital has accumulated substantial experience in managing postoperative recurrence. Building on this, we have progressively developed radiation therapy strategies tailored to these patients. Today, we are capable of designing individualized radiotherapy plans based on the primary tumor location and specific recurrence risks, ensuring more targeted and effective interventions.
With the emergence of new therapeutic agents—such as immunotherapies and targeted drugs—the integration of radiotherapy with systemic treatments has opened up new possibilities in the adjuvant setting. One such recent initiative is our clinical study investigating radiotherapy combined with disitamab vedotin in HER2-overexpressing patients. This work has offered valuable new insights. In the past, we focused mainly on treating HER2-positive patients during advanced stages after disease progression. However, we have now observed that HER2-overexpressing patients tend to progress more rapidly after surgery compared to those with low or negative HER2 expression. This finding suggests the need for more precise, biomarker-driven therapeutic planning even in the adjuvant phase.
Additionally, recent years have seen significant advances in kidney-sparing treatments for UTUC. While pharmacological therapies have brought new hope for organ preservation, analysis from several centers indicates that local recurrence remains a major challenge in this setting.
Given this, we are now considering applying the successful strategies we’ve used in adjuvant therapy to kidney-sparing approaches. At Peking University First Hospital, we may explore a combination of intracavitary therapy, systemic pharmacotherapy, and radiotherapy—a regimen already well established in bladder cancer and associated with excellent outcomes. We believe that adapting this approach to UTUC could similarly offer meaningful survival benefits for patients seeking organ preservation.
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What future directions are worth exploring for disitamab vedotin in the treatment of UTUC?
Professor Qi Tang: Disitamab vedotin has demonstrated particularly promising efficacy and safety in the treatment of advanced metastatic UTUC. In the RC48-C005/C009 studies, UTUC patients accounted for over 50% of the study population, with a subgroup objective response rate (ORR) of 50%, comparable to that observed in bladder cancer. In the RC48-C014 study, the UTUC population comprised 58.5% of participants, and the ORR in this subgroup was an impressive 62.5%.
Additionally, a large-scale real-world study led by the CUDA-UTUC collaborative group in China included 198 patients with metastatic UTUC. Results showed an ORR of 58.6% for those receiving disitamab vedotin combined with immunotherapy, while the incidence of grade ≥3 adverse events was only 19.7%, further confirming the drug’s remarkable efficacy and manageable safety profile.
It is also noteworthy that neoadjuvant treatment combining disitamab vedotin with immunotherapy has shown substantial promise. In the WUTSUP-02 study conducted by West China Hospital, 20 high-risk UTUC patients (cT2-4N0-2M0) received four cycles of the combination therapy. Among them, 14 patients underwent radical nephroureterectomy, achieving a pathologic complete response (pCR) rate of 21.43% (3/14) and an ORR of 78.57% (11/14). Furthermore, this combination has also performed well in kidney-sparing therapy for high-risk UTUC patients, demonstrating both efficacy and a favorable safety profile. Several research centers across China are actively exploring this approach.
In summary, the emergence of HER2-targeted ADCs like disitamab vedotin offers a completely new class of therapeutic options for UTUC. From advanced metastatic cases unsuitable for surgery to perioperative settings—including adjuvant, neoadjuvant, and kidney-sparing strategies—these therapies have opened new frontiers in treatment and hold the potential to significantly improve both clinical outcomes and quality of life for UTUC patients.
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Looking ahead, what plans does the CUDA-UTUC collaborative group have to further advance UTUC diagnosis and treatment in China?
Professor Xuesong Li: The CUDA-UTUC collaborative group has developed a comprehensive and forward-looking agenda for the future. As one of several subgroups under the Chinese Urological Association of the Chinese Medical Doctor Association (CUDA), the UTUC group is among the most active, with the widest and most in-depth multi-center collaboration.
Building on this solid foundation, we submitted a proposal earlier this year to elevate the UTUC collaborative group to a full academic working group—and this proposal has been officially approved by the CUDA leadership. Accordingly, we plan to host the first UTUC academic group meeting during the upcoming CUDA Annual Conference in Zhuhai on June 14–15.
This professional meeting will focus on several key objectives. First, we will address the unique challenges UTUC presents as a specialized disease entity. Second, we will release multi-center clinical research initiatives to be implemented across partner institutions. Third, we will clarify the goals and development roadmap for establishing national consensus guidelines. And importantly, we aim to deepen cross-institutional collaboration under the academic group framework, raising the quality and impact of UTUC research in China.
We also hope this conference will help strengthen China’s connection to the international UTUC research community, enabling broader and deeper exchanges and collaborations.
We sincerely invite colleagues from across the country to join us in Zhuhai to witness and participate in this milestone academic gathering. We look forward to seeing everyone in this beautiful coastal city, working together to shape the future of UTUC care in China.
· Xuesong Li
· Qi Tang
· Xiaoying Li
