In select patients with imperative or elective indication, kidney-sparing surgery (KSS) is an option for the treatment of patients with high-risk UTUC as an alternative to upfront RNU [50]. Similar to conservative treatment of early invasive bladder cancer (staged pT1), a major concern of conducting kidney-sparing treatment in high-risk UTUC is the risk of progression in case of treatment failure, which may have a negative impact on survival. Imperative indications for nephron-sparing surgery include patients with solitary kidneys, bilateral disease, or severe renal insufficiency who would be rendered functionally or anatomically anephric after RNU. Following demonstration of the technical feasibility with acceptable oncologic outcomes in patients with imperative indication, investigators have expanded the indication for KSS to elective cases aiming to ensure maximum kidney function after treatment [51–53].

One critical aspect of KSS in high-risk UTUC is proper patient selection to avoid the risk of treatment failure. Another issue is the accuracy of pathologic staging and grading given the currently available endoscopic techniques. In this respect, a detailed diagnostic ureterorenoscopy using flexible instruments is imperative prior to consideration of any nephron-sparing approach in high-risk UTUC to evaluate the extent of the tumor lesion and obtain representative biopsies as well as a cytology of the tumor-affected renoureteral unit [54, 55, 56–58]. However, the accurate clinical and pathological staging of upper tract tumors can be difficult as with the current available endoscopic equipment it is often not possible to obtain a full-thickness biopsy to evaluate for muscle invasion. In this respect, a high degree of concordance has been observed between tumor grade assessed on endoscopically obtained upper tract biopsies compared to tumor grade (84–91 %) [59–61] and stage at the time of RNU [62]. Therefore, tumor grade at biopsy is considered a strong surrogate marker for stage and, thus, for the final clinical decision-making for a kidney-sparing approach. Omission to perform a biopsy at diagnostic ureterorenoscopy inherits the risk of understaging as macroscopic tumor appearance does not reliably predict tumor grade. In this respect, Thompson et al. demonstrated that 21 % of tumors thought to be low grade on visual inspection were subsequently found to be high grade on pathologic review of RNU specimen [53].

Notably, in patients with elective or imperative indication opting for a kidney-sparing approach lifelong surveillance of the upper tracts and bladder is obligatory as the risk of recurrence ranges considerably (3–63 %) [63, 64] and may even occur after more than 15 years of follow-up [65].

Variations in primary tumor size, location, and grade decide on the surgical method for nephron-sparing treatment in high-risk UTUC. Basically, KSS in UTUC includes either endoscopic resection or segmental/total ureterectomy. Endoscopic resection and laser-based ablative techniques can be performed via either retrograde or antegrade manipulation. Ureterectomy is feasible for high-grade, infiltrative ureteral lesions and carcinoma in situ (CIS) of the ureter.

For endoscopic management of high-risk UTUC access to the tumor can be established via either an antegrade or retrograde approach. Using semirigid or flexible instruments tumors can be easily visualized and ablation of the tumor can be performed using electrocautery, holmium:YAG, or neodymium:YAG lasers. The main benefits of the retrograde approach include maintaining a closed urinary system and less morbidity than the antegrade approach. In cases of larger tumors, lesions in the lower renal calyces not accessible by retrograde ureteroscopy, and in patients with urinary diversions creating difficult retrograde access, an antegrade approach may be more sensible as larger instruments can be used and direct access to the affected calyx can be easily gained.

Select series reporting outcomes after endoscopic KSS for high-risk UTUC are outlined in Table 6.3. As disease-specific mortality in UTUC has been shown to be independently associated only with grade and body mass index which have been identified as predictors of DSM [78–80] it seems promising to take a closer look to the reported survival rates based on the type of treatment in high-risk UTUC. Yet, studies on outcomes after ureterorenoscopic treatment of high-risk UTUC are scarce and subjected to selection biases and small patient numbers. One study reported that among 48 patients with low-grade UTUC disease-specific survival rates between those treated with ureterorenoscopy and RNU for low-grade tumors did not differ significantly at 5 years (86 % vs. 87 %). Among the 68 patients with high-grade tumors only 12 underwent endoscopic treatment while the remaining 56 were subjected to upfront RNU. No significant differences were noted between both groups (68 % vs. 75 %, respectively; p = 0.52), but conclusions relating to high-grade tumors are limited due to the low number of included patients treated with ureteroscopic ablation [81].

High rates of upper tract recurrence after ureterorenoscopic treatment for high-risk UTUC have been reported with grade-related 5-year recurrence-free survival of 63 %, 34 %, and 17 % in G1, G2, and G3, respectively (p = 0.011) [78, 82]. These results show that recurrence rates in patients undergoing NSS for high-grade UTUC are ultimately high which underscore the importance of close and lifelong follow-up. The need for salvage RNU in patients stratified by grade is a higher rate of RNU for high rather than low-grade tumors (25 % vs. 17 %). Similarly, Cutress et al. demonstrated 5-year renal unit survival of 96 %, 71 %, and 20 % in G1, G2, and G3, respectively (p < 0.001) [82]. Complications related to ureteroscopic treatment include distal ureteral strictures with rates up to 17 %, sepsis in up to 11 %, and ureteral perforation in up to 9 % of cases. Care must be taken during ablation with electrocautery or lasers to prevent perforation of the ureter, as the thickness is less than the bladder. Therefore, it is important to maintain good visualization during ablation as poor intraoperative vision may lead to difficulties in achieving complete tumor ablation endoscopically, with the potential of leaving residual tumor behind, thereby possibly resulting in high rates of recurrence [83].

Percutaneous management of high-risk UTUC may be an option for larger tumors in the renal calyces as larger instruments can be inserted into a particular renal calyx. Additionally, in patients with urinary diversions or when access in a retrograde fashion is difficult to be achieved, percutaneous treatment may be an option.

As with other series on KSS in high-risk UTUC, results on percutaneous treatment are poorly stratified by grade which limits meaningful conclusions. Recurrence rates in the upper urinary tract range significantly from 12 to 66 % with one study demonstrating higher rates in high- vs low-grade disease (31 % vs 5 %) [84]. The most recent and largest study consisted of 89 renal units treated by percutaneous nephroscopy (PCN) of which 39 tumors were high grade. A second look nephroscopy was routinely performed within 1 week with re-resection if necessary, and a third look nephroscopy done at 3 months to reevaluate for recurrence. Authors reported a recurrence rate of 33 % with higher rates in high- (38 %) vs. low-grade (30 %) tumors [85].

Main complications following percutaneous management of UTUC include blood transfusions due to hemorrhage (13 %) and risk of stricture formation (5 %). Additionally, tumor seeding along the percutaneous nephrostomy tract has been described [85–87].

In patients with high-risk UTUC some studies have demonstrated the clinical feasibility of intracavitary adjuvant instillation therapy. In one study of 89 patients with low- and high-grade UTUC who were treated with PCN, 50 patients received a 6-week course of BCG and 39 patients with no adjuvant therapy. No difference was noted in recurrence when stratified by stage and grade [88]. Although study numbers were small, the results of this study suggest no significant role for adjuvant BCG in patients with Ta/T1 UTUC and no evidence of CIS, regarding prevention of recurrence or progression. This may be due to inherent differences in the biology between UTUC and urothelial bladder cancer, or incomplete resection of UTUC, thereby leaving residual tumor behind. Positive response rates (defined as negative cytology on follow-up) to a 6-week course of BCG were noted to range from 64 to 100 % with subsequent rates of recurrence noted in 9–50 % of patients. In a case series reporting outcomes in 11 patients with pure CIS of the upper tract treated with BCG compared to five patients treated with immediate RNU, no difference in 5-year RFS (78 % vs 67 %) and 5-year DSS (91 vs. 80 %) was noted [89]. Therefore, these good response rates suggest that BCG should be evaluated in clinical trials in patients with pure or concomitant CIS of the upper tract. Table 6.4 provides an overview of selected series reporting outcomes after intracavitary treatment for UTUC.