Editor’s Note: Radical nephroureterectomy (RNU) remains the gold standard treatment for upper tract urothelial carcinoma (UTUC). However, some patients with a solitary kidney or insufficient renal reserve may require alternative approaches to preserve kidney function. In recent years, advancements in systemic drug therapy and various endoscopic focal treatment techniques have provided kidney-sparing options for such patients. Nonetheless, large-scale case reports or prospective studies remain scarce. At the 31st Urology Academic Conference (CUA 2024), organized by the Chinese Medical Association and the Chinese Urological Association, Dr. Qiang Wei and  Yige Bao from West China Hospital, Sichuan University, presented their report on multimodal kidney-sparing treatment in 62 patients with high-risk localized UTUC.

UTUC Overview and High-Risk Stratification

UTUC, which includes renal pelvis and ureteral cancers, is a relatively rare type of urothelial carcinoma (UC), with a global incidence of approximately 2 per 100,000 and representing only 5-10% of all UC cases . However, the proportion of UTUC among UC patients in China may be higher. According to a 2018 report by the CUDA-UTUC collaborative group, UTUC accounted for an average of 17.9% of UC cases in 32 hospitals across China .

Despite the relatively low incidence of UTUC, its diagnosis and treatment remain controversial. Due to the challenges in tumor staging, UTUC risk stratification is used to guide prognosis and treatment decisions. High-risk UTUC includes patients with any of the following features: multifocal tumors, tumor size ≥2cm, high-grade cytology, high-grade biopsy by ureteroscopy (URS), local invasion on CT, hydronephrosis, history of radical cystectomy for high-grade bladder cancer, or specific histological subtypes . Clinically, the majority of UTUC cases are classified as high-risk according to the EAU guidelines. At West China Hospital, 94.5% of 110 UTUC patients were assessed as high-risk.

Treatment Approach and Kidney-Sparing Strategy

Currently, radical nephroureterectomy (RNU) remains the gold standard for UTUC treatment. However, kidney-sparing surgery is an option for low-risk patients, with techniques including ureteroscopic or percutaneous tumor resection, laser or cryoablation, segmental ureterectomy with anastomosis or reimplantation, and use of mitomycin gel. Individual patient factors such as a solitary kidney, bilateral UTUC, or chronic kidney disease are indications for kidney-sparing treatment. Additionally, factors like patient preference, comorbidities, and sequential development of bladder cancer followed by UTUC are also considerations. Nevertheless, kidney-sparing treatment comes with higher risks of disease progression and mortality, necessitating a careful balance between tumor control and renal function preservation. Comprehensive treatment modalities combining surgery, systemic therapy, and close follow-up are essential for minimizing postoperative recurrence risk.

Study and Outcomes of 62 Patients Treated at West China Hospital

Since January 2020, 62 patients with high-risk localized UTUC have received comprehensive kidney-sparing treatment at West China Hospital. The surgeries included segmental ureterectomy with anastomosis (14 cases) and ureteroscopic thulium laser ablation (49 cases). Additionally, local or systemic therapies included chemotherapy ± immune checkpoint inhibitors (ICIs), vedicitumumab (RC48) ± ICIs, ICIs alone, or radiotherapy. The median patient age was 75 years (range: 34–93), with 20 cases of renal pelvis tumors and 43 cases of ureteral tumors. Among them, 48 patients had associated hydronephrosis, the average tumor diameter was 1.87cm, 32 patients had high-grade tumors, and four patients presented with variant histology. The cohort included nine patients with a solitary kidney, and five each with bilateral UTUC or renal insufficiency.

The initial report presents data with a median follow-up of 15 months (range: 6–53 months); 16 patients were followed up for more than two years. Among the 63 patients, 28 experienced recurrence, including 22 with in-situ recurrence and six with bladder implant recurrence. Of the patients with recurrence, nine underwent salvage RNU. The one-year kidney preservation success rate was 93.7%, and the two-year success rate was 88.9%. Four patients died, with one tumor-specific death. Subgroup analysis showed no significant difference in disease-free survival between segmental ureterectomy and endoscopic ablation patients (P = 0.74). However, endoscopic ablation patients had higher nephron-sparing survival than those undergoing segmental ureterectomy (P = 0.049). Among patients who underwent endoscopic ablation, there was no significant difference in disease-free survival between those with or without systemic therapy (P = 0.25).

In the RC48 ± ICIs kidney-sparing treatment cohort (n = 33), the median follow-up was 12 months (range: 6–33 months). Nine patients experienced recurrence, including nine in-situ recurrences and one bladder implant recurrence. Two patients underwent salvage RNU, and the one-year kidney preservation success rate was 92.8%. The 15-month local recurrence-free survival rate was 71.4% (20/28). One patient died, with zero tumor-specific deaths, and the 15-month overall survival rate was 96.4% (27/28). Furthermore, patients treated with kidney-sparing therapy showed smaller changes in renal function and higher mean eGFR levels (measured one to 12 months after treatment) compared to those who received radical treatment.

Conclusion The proportion of UTUC among UC patients in China may be higher. Although radical surgery remains the gold standard, some carefully selected patients with high-risk localized UTUC can achieve kidney-sparing treatment through a comprehensive multimodal approach. These patients’ survival outcomes (OS and CSS) may not be significantly inferior to those undergoing RNU, and there are clear benefits in preserving renal function. Achieving successful kidney-sparing treatment depends on thorough understanding of the tumor, complete local control, the effectiveness of systemic therapies, and diligent follow-up.

This report underscores the importance of tailored approaches in the treatment of high-risk localized UTUC and highlights the evolving strategies in kidney preservation while maintaining oncological safety.