Editor’s Note: The 2025 Annual Meeting of the Chinese Urological Association (CUDA), held from June 12 to 15 in the romantic city of Zhuhai, brought together leading experts under the theme “Healthy China, Urology First.” At the conference, Professor Jiwei Huang from Renji Hospital, Shanghai Jiao Tong University School of Medicine, delivered a compelling presentation on neoadjuvant therapy for upper tract urothelial carcinoma (UTUC). In an exclusive interview with Oncology Frontier – UroStream, he further discussed his team’s research and practical experience in this evolving field.Oncology Frontier – UroStream: When considering neoadjuvant therapy for UTUC, how do you determine the appropriate patient population and treatment strategy?
Professor Jiwei Huang: Neoadjuvant therapy for UTUC is likely to become a major focus in future clinical research and practice. Overall, UTUC has a poorer prognosis than bladder cancer, making it even more crucial to apply perioperative treatments to improve outcomes. Current treatment modalities include chemotherapy, targeted therapies such as antibody-drug conjugates (ADCs), and immunotherapy.
Platinum-based neoadjuvant chemotherapy has shown some efficacy, but its significant side effects limit its use—many patients are unable to tolerate its toxicity. We have conducted studies on neoadjuvant single-agent immunotherapy, which had fewer side effects, though the efficacy was not entirely satisfactory. On the other hand, ADC-based therapy, especially when combined with immunotherapy, may yield more promising results.
In terms of patient selection for neoadjuvant therapy, two groups appear to be the most suitable: The first group includes patients with locally advanced disease who may face challenges with surgery or are unlikely to achieve an R0 resection. These patients may become operable or eligible for curative surgery after neoadjuvant treatment. The second group comprises patients with limited renal function, poor surgical tolerance, or those with high-risk localized disease—such as muscle-invasive tumors or high tumor burden—who would typically require complete ureter and kidney removal. With drug-based treatment, some of these patients may be able to undergo kidney-sparing therapy.
Oncology Frontier – UroStream: Could you tell us more about your center’s research efforts in the field of neoadjuvant therapy for UTUC? How do you view the potential of novel therapies such as immunotherapy, targeted drugs, and ADCs?
Professor Jiwei Huang: Our center has initiated or is currently conducting several clinical studies focused on neoadjuvant therapy for UTUC. One of them is a single-arm Phase II study investigating neoadjuvant treatment with toripalimab monotherapy in patients with high-risk UTUC.
As background, the internationally known PURE-01 trial evaluating pembrolizumab monotherapy as neoadjuvant therapy in high-risk muscle-invasive bladder cancer (MIBC) reported a relatively high pathological complete response (pCR, ypT0N0) rate of 42%, along with a clear benefit in recurrence-free survival (RFS). However, the corresponding PURE-02 trial for high-risk UTUC patients showed a pCR rate of only 14.3%.
In our study, patients with high-risk UTUC received four preoperative cycles of toripalimab. The results were encouraging: a pCR rate of 20% and a pathological response rate (≤ypT1N0) of 43%.
Building on immunotherapy, combining it with chemotherapy, targeted agents, or ADCs may further improve efficacy. Our center is also leading a nationwide multicenter study exploring the combination of ADCs with immunotherapy, and the data thus far suggest promising efficacy and safety. We are in the process of submitting the results for publication and look forward to sharing them with the broader community soon.
Overall, while combination regimens appear to hold strong potential for enhancing the effectiveness of neoadjuvant therapy in UTUC, chemotherapy still remains the mainstay in current clinical practice and continues to offer meaningful benefit for selected patients.
Oncology Frontier – UroStream: For patients who respond well to neoadjuvant therapy, is kidney-sparing treatment a viable option? How should post-treatment management be strengthened to reduce the risk of recurrence?
Professor Jiwei Huang: For high-risk UTUC patients who require kidney preservation, if neoadjuvant therapy leads to significant tumor shrinkage or even downgrading to low-risk disease, then kidney-sparing surgery may be considered in selected cases.
Under the guidance of the CUDA UTUC working group, our center has led the DISTINCT1 study, and we are now expanding into the larger-scale DISTINCT2 study. Both aim to evaluate whether neoadjuvant therapy can downstage high-risk UTUC patients and make them eligible for kidney-sparing surgery. Other leading institutions across China, such as West China Hospital and the Fudan University Shanghai Cancer Center, are also actively exploring this treatment strategy.
For patients undergoing kidney-sparing surgery, rigorous post-treatment surveillance is essential to ensure oncological safety. In the future, we hope to leverage molecular or genomic biomarkers to enhance monitoring. Non-invasive liquid biopsy techniques—such as blood-based ctDNA or urine-based utDNA—may offer real-time, dynamic surveillance and help address the limitations of traditional cystoscopy, ureteroscopy, and urine cytology.
Additionally, for these high-risk patients, there is an ongoing need to explore whether adjuvant therapy after surgery could further reduce the risk of recurrence. This will be a key focus in optimizing long-term outcomes.
Professor Jiwei Huang
