Editor’s Note: Upper tract urothelial carcinoma (UTUC), encompassing renal pelvic and ureteral cancers, is relatively rare, with unique characteristics in the Chinese population, such as distinct disease features and molecular biology profiles. The 8th West China Uro-Oncology Tianfu Academic Conference, recently held in Chengdu, provided a platform to discuss how to better address the challenges in UTUC treatment and improve patient outcomes. In this event, Oncology Frontier interviewed Dr. Yige Bao from West China Hospital of Sichuan University, who shared insights into personalized perioperative treatment of UTUC with ADC drugs and the hospital's clinical experiences.Characteristics of Upper Tract Urothelial Carcinoma (UTUC)
UTUC accounts for about 10% of all urothelial carcinomas (UC), with a global annual incidence of approximately 2 per 100,000 people. However, data from the 2018 Chinese UTUC Collaboration Group showed that UTUC accounts for 17.9% of all UC cases in China, surpassing global proportions. Despite sharing the urothelial carcinoma classification with bladder cancer (UBC), UTUC differs significantly in molecular characteristics, anatomy, clinical decision-making, and management strategies.
Radical nephroureterectomy (RNU) remains the gold standard for UTUC treatment. Over recent years, West China Hospital has observed a steady increase in RNU cases, ureteroscopic evaluations, and procedures. Both international studies and West China data demonstrate that high-quality RNU can achieve a 5-year cancer-specific survival (CSS) rate of 60%–70%.
Risk Stratification in UTUC
Both domestic and international guidelines emphasize risk stratification in UTUC diagnosis and treatment. The 2024 CSCO Urothelial Carcinoma Diagnosis and Treatment Guidelines outline criteria for low-risk and high-risk classifications.
Low-risk cases feature characteristics such as solitary tumors, size <2 cm, low-grade cytology or biopsy, and no evidence of local invasion on CT or MRU. High-risk patients, by contrast, exhibit features like multifocal disease, tumor size >2 cm, hydronephrosis, high-grade cytology or biopsy, or local invasion on imaging.
West China Hospital’s urology data indicates that only 26.73% of patients treated between 2014 and 2019 had stage T1 tumors. By November 2022, merely 7 out of 111 UTUC cases were classified as low-risk, reflecting the high prevalence of advanced disease in China, necessitating personalized treatment approaches.
Perioperative Treatment for High-Risk UTUC
Surgical treatment alone is often insufficient for high-risk UTUC, as the two-year recurrence rate can reach approximately 40%. UTUC-related mortality frequently results from distant metastases rather than localized disease, underscoring the limitations of local therapies in controlling micrometastatic lesions.
Given the sensitivity of urothelial carcinoma to chemotherapy, immune checkpoint inhibitors (ICIs), and antibody-drug conjugates (ADCs), systemic treatments such as neoadjuvant or adjuvant therapies may offer effective tumor control. Although neoadjuvant treatment is well-established in cancers such as breast, colorectal, and bladder cancers, it remains underexplored for high-risk UTUC, with limited small-sample retrospective studies available.
Advantages and Challenges of Neoadjuvant Therapy
Neoadjuvant therapy before definitive surgery offers several advantages. It can target micrometastatic disease early, leveraging intact retroperitoneal blood flow and better patient tolerance. Additionally, it allows for individualized treatment by providing in vivo drug sensitivity data and biomarkers, while downstaging tumors may reduce surgical complexity and complications.
However, challenges remain. Neoadjuvant chemotherapy shows limited improvement in overall survival (5%–7%). In non-responders, delayed surgery may lead to tumor progression or metastasis. Furthermore, chemotherapy is less effective against variant histology types, and overtreatment risks remain for organ-confined tumors without micrometastases. Neoadjuvant therapy can also cause local tissue edema and adhesions, complicating surgery.
Exploring ADC-Based Neoadjuvant Immunotherapy
West China Hospital is leading multiple clinical trials to optimize perioperative treatments for high-risk UTUC. The WUTSUP-02 study, a phase II trial, evaluates the combination of vedicitumab and toripalimab for neoadjuvant therapy in localized high-risk UTUC. Preliminary results from 20 cases showed a pathological complete response (pCR) rate of 20% and an overall response rate (ORR) of 57%.
Building on these findings, a phase II trial investigates sequential vedicitumab-toripalimab adjuvant therapy following neoadjuvant treatment for locally advanced UTUC (cT2-4N0-2M0). Initial data indicate promising efficacy, with more robust results anticipated.
Adjuvant Chemotherapy and West China Experience
The POUT phase III study demonstrated the efficacy of adjuvant platinum-based chemotherapy in UTUC patients, significantly improving disease-free survival (DFS) (HR=0.45) and reducing distant metastasis or mortality risks (HR=0.48). Additionally, West China data highlight the challenges of reduced renal function post-RNU, often complicating chemotherapy administration.
Since 2020, West China Hospital has accumulated data on 78 high-risk UTUC patients treated with ADCs to preserve renal function. Preliminary findings indicate no rescue RNU cases or distant metastases, with promising DFS and overall survival rates.
Conclusion
West China Hospital has developed comprehensive diagnostic and treatment protocols for UTUC, spanning low-risk to high-risk patients. These personalized strategies aim to balance tumor control with renal function preservation, incorporating the latest advancements in ADCs and immunotherapy.
The hospital’s contributions extend beyond clinical practice to guideline formulation, including drafting the CUDA UTUC Consensus and the CUA UTUC Diagnosis and Treatment Guidelines. These efforts underscore West China Hospital’s pivotal role in advancing UTUC management and improving patient outcomes in China.
Yige Bao, MD, PhD
Associate Professor, West China Hospital of Sichuan University
- Director, Department of Urology, West China Hospital Ganzi Hospital, Sichuan University
- Deputy Chair of the Youth Committee, Chinese Urological Association Physicians Section
- Youth Committee Member, Urology Professional Committee, Chinese Research Hospital Association
- Deputy Chair of the Youth Committee, Sichuan Urological Association
- Youth Member, Sichuan Reproductive Medicine Committee
Dr. Bao has published over ten papers in international and domestic journals, contributed to one academic monograph, and serves as the principal investigator for a National Natural Science Foundation of China (NSFC) Youth Grant. He has also participated in drafting a national expert consensus.
