Upper tract urothelial carcinoma (UTUC) refers to urothelial carcinoma that originates from the renal pelvis and ureter. This malignancy is relatively rare, comprising only 5% to 10% of all urothelial carcinomas (1). UTUC presents a greater clinical challenge compared to bladder cancer. Chinese patients with UTUC typically present with seemingly good health, yet frequently demonstrate adverse pathological characteristics, such as high-grade pathology and muscular invasion (2). Radical nephroureterectomy (RNU) with cystectomy cuff is the standard treatment for localized high-risk UTUC. However, RNU is associated with a spectrum of postoperative complications and potential renal function impairment in patients. Cisplatin-based postoperative adjuvant therapy is difficult to tolerate in some patients (3), and complications such as chronic kidney disease after RNU may even increase the overall mortality rate (4). Additionally, elderly patients may experience poorer outcomes after RNU compared to their younger patients (5). Kidney-sparing surgery (KSS), including segmental ureterectomy (SU) and endoscopic surgery, may have shorter operating time than RNU, reduce postoperative complications, and protect renal function (6). It has demonstrated satisfactory efficacy in low-risk UTUC patients, but its ability to eliminate tumor cells in high-risk cases is still controversial.

As surgical technology advances and the concept of precision medicine evolves, an increasing number of patients and clinicians are opting for organ-preserving surgical techniques to treat tumors instead of radical surgery under the premise of ensuring the prognosis of oncology. The 2025 version of the European Association of Urology (EAU) guidelines underscores the increasing importance of KSS in managing UTUC. However, there remains a scarcity of robust evidence regarding the oncological outcomes of KSS in high-risk UTUC treatment, necessitating further clinical research to substantiate its efficacy. Apart from the inherent risk factors associated with high-risk UTUC, additional variables influencing the prognosis of patients with high-risk UTUC necessitate further validation. Therefore, we conducted this study at our center to further evaluate the safety and feasibility of KSS in high-risk UTUC patients and provide experience for KSS in high-risk UTUC patients.

KSS encompasses surgical approaches ranging from SU to endoscopic treatment (7). With the development of surgical technology and the deepening of the concept of precision medicine treatment, organ-preserving minimally invasive surgery has become the dominant paradigm in contemporary oncology therapeutic strategy. RNU combined with bladder sleeve resection is still the gold standard surgical treatment for high-risk renal pelvic and ureteral cancer (1). Even in cases of metastatic UTUC (mUTUC), combining nephroureterectomy with systemic therapy has been shown to improve survival in patients with early local disease (T1–T2) compared to systemic treatment alone (8). However, RNU may result in a range of complications, and the risk of perioperative complications is similar between open RNU and laparoscopic RNU (9, 10). One study showed that 14.1% of patients had postoperative complications after RNU, and 3.7% of them were classified as severe complications (11). Compared with RNU, KSS preserves the ipsilateral kidney by segmental ureterectomy or endoscopic direct tumor elimination. In patients with low-risk UTUC, a large number of studies have shown that there is no significant difference in the oncological outcomes between KSS and RNU (12–14). In recent years, there have been more studies on KSS for high-risk UTUC.A retrospective study of 252 participants showed that KSS was also a feasible choice for patients with UTUC, not only in low-risk patients, but also in high-risk patients with normal contralateral kidneys (15). In our study, the operation time and intraoperative blood loss in the KSS group were significantly lower than those in the RNU group. In terms of complications, although there was no statistically significant difference between the two groups, there were no complications higher than Clavien II in the KSS group, which may be partly why patients with high quality of life expectations prefer to receive KSS treatment.

When possible, one of the reasons why people prefer KSS is its protection of renal function. Since RNU requires removal of the entire ureter segment and ipsilateral kidney, it carries a consequential risk of postoperative renal functional impairment (16, 17). Studies report that even patients with normal preoperative, renal function decreases by one-third after RNU and does not show evidence of recovery over time (18). Conversely, research on KSS demonstrates significantly superior eGFR levels and eGFR preservation rates in patients undergoing segmental ureterectomy compared to RNU cohorts at both 1-month and 1-year postoperative intervals (19). Another study showed that while KSS exhibits significantly better eGFR outcomes at the 3-month postoperative mark versus RNU, no statistically significant differences were observed at 2 years (P = 0.081) or 5 years (P = 0.304) post-surgery (20). The study by Huang Z et al. showed a significant increase in mean postoperative eGFR of 4.60 ml/min/1.73 m² in SU group (21). In this study, the mean preoperative eGFR values were 68.91 ml/min/1.73 m² in the KSS group versus 63.36 ml/min/1.73 m² in the RNU group. At 6 months postoperatively, these values measured 71.79 ml/min/1.73 m² and 52.62 ml/min/1.73 m², respectively (p<0.001), while the change rate of eGFR in KSS group and RNU group were 13.0% and -16.2%, respectively (p<0.001). Concomitantly, there were significant differences in postoperative creatinine levels and rates of change between the two groups, reflecting the advantages of KSS in preserving renal function. According to our clinical experience, KSS may protect renal function because most high-risk UTUCs have hydronephrosis, and KSS surgery relieves tumor obstruction while preserving the kidney (Figure 2).

Under the condition of ensuring the prognosis of oncology, comprehensive treatment based on KSS is a reasonable choice for the treatment of upper urinary tract urothelial carcinoma. Adjuvant therapy includes bladder instillation, immunotherapy, systemic chemotherapy and radiotherapy. Adjuvant therapy can improve the prognosis and prolong the life of patients (22–26). In our study, the two groups of patients received these postoperative adjuvant therapies, and there was no statistically significant difference between the two groups of patients receiving various adjuvant therapies. The prognosis of patients in RNU group and KSS group is the focus of this study. A study evaluated and analyzed the recurrence-free survival, overall survival, and cancer-specific survival of SU and RNU in high-risk ureteral carcinoma, respectively, and found no significant difference (21). Chen Y et al. analyzed endoscopic cryoablation versus radical nephroureterectomy in high-risk UTUC patients and showed no significant difference in 2-year OS (82% vs 84%), PFS (73% vs 71%), and IVRFS (81% vs 83%) rates (27). These are similar to our results. In our study focusing on high-risk UTUC, where no statistically significant differences existed between the KSS and RNU groups regarding factors such as tumor stage or adjuvant therapy, the 3-year overall survival rate was 88.1% and78.5%, 3-year DFS was 60.3% and 53.9%, 3-year MFS was 82.1% and 71.9%, 3-year IVRFS was 80.2% and 69.3%, respectively. Notably, all intergroup differences lacked statistical significance (p>0.05). COX regression analysis also demonstrated that surgical method was not associated with oncological prognosis.

In order to explore more factors that may affect the prognosis of patients with UTUC, in addition to the high risk factors for the diagnosis of high-risk UTUC, multivariate COX regression analysis showed that tumor pathological stage were independent predictors of OS, DFS and MFS. The new version of the guidelines pointed out that the main prognostic factor of UTUC was tumor pathological stage (1), which was the same as our research results. According to our clinical experience, the pathological stage of tumor and other high-risk factors can often affect the difficulty of operation, resulting in the difference of intraoperative blood loss. Therefore, intraoperative blood loss may have the potential value of indirectly evaluating the prognosis of oncology and can be used as one of the reference indicators of clinical prognosis. In addition, creatinine was considered an independent predictor of OS (P = 0.04) but eGFR was not, suggesting that creatinine values may be more sensitive than eGFR in some settings. Elevated creatinine is often associated with hydronephrosis, which is a weak risk factor for UTUC, and multiple studies have shown that it is associated with poor prognosis for UTUC (28, 29). Preoperative creatinine has prognostic value for OS, but not for tumor specific endpoints (DFS, MFS, IVRFS). In order to clarify this difference, preoperative creatinine may affect OS by increasing the burden of competitive risk comorbidity. However, tumor recurrence and metastasis are more directly dependent on the invasiveness of the tumor itself, such as its pathological stage. In summary, patients presenting with elevated preoperative creatinine, advanced pathological stage, and greater intraoperative blood loss may have a poorer prognosis. This suggests that clinicians should adopt the most aggressive and individualized strategies regarding adjuvant therapy and follow-up planning for such patients. Although this study is retrospective and observational, these markers provide a valuable direction for developing a comprehensive prognostic model for UTUC in the future.

Admittedly, due to the low incidence of UTUC, the sample size we collected was limited. And for ethical reasons, randomization or blinding was not possible, so this study was a non-randomized retrospective study. Although most baseline data were not significantly different between the two groups, there were unidentified confounding variables. Whether KSS is applicable to all high-risk UTUC is still controversial. In the future, well-designed multicenter, randomized controlled or prospective large-sample studies are still needed to further verify the clinical application value of KSS in high-risk UTUC patients, especially for high-risk UTUC defined according to EAU strong standards.

In conclusion, this study shows that the oncological prognosis of KSS is comparable to RNU, and that KSS has a significant renal function protection advantage at short-and medium-term follow-up, providing evidence for the feasibility of renal sparing therapy in high-risk UTUC patients. In addition, we found factors that may affect the prognosis of patients (including pathological stage, preoperative creatinine, intraoperative blood loss) through analysis, which will provide an important basis for us to predict the disease development more accurately and for personalized adjustment of clinical treatment plan. Despite these insights, the findings must be interpreted considering the study’s limitations, including its single center retrospective design and the potential selection bias and insufficient statistical power that may arise from small sample sizes (especially in the KSS group), which may limit the generalizability of extrapolation of research results. There is a pressing need for prospective, multi-institutional studies with larger cohorts, longer follow-up, and standardized patient selection criteria to definitively validate the role of KSS in this high-risk setting.