EAU 2023: State-of-the-Art Lecture: Improvement in Technologies and Drugs to Support Kidney Sparing Surgery

(UroToday.com) The 2023 EAU annual meeting included an EAU guideline session on effective treatment in upper tract urothelial tumors, featuring a state-of-the-art presentation by Dr. Joyce Baard discussing improvement in technologies and drugs to support kidney sparing surgery.

Dr. Baard started her presentation by highlighting the EAU Guidelines’ breakdown of low vs high risk upper tract urothelial carcinoma: 

utuc.jpgKidney sparing surgery in selected patients with low risk disease may be appropriate, with a risk adapted approached leading to comparable oncologic results, with the benefit of preserving renal units. Highlighting data from her own institution, Dr. Baard notes that 75 renal units have been treated with kidney sparing surgery (18.7% high grade), and over a median follow-up of 47.8 months, the recurrence rate is 44.6%, intravesical recurrence rate is 68%, and cancer specific survival is 86.0%. Additionally, disease upgrading was found in 21.3% of cases, at a mean of 26.8 months from diagnosis. Treatment conversion to more radical surgery occurred in 30.1% of cases, at a mean of 18.7 months from diagnosis.

Looking at the literature, recurrences after endoscopy are associated with increased recurrence risk and increased intravesical recurrence (after radical nephroureterectomy 16.7%-46%; proceeded by diagnostic ureteroscopy 39.2-60.7%): 


However, Dr. Baard emphasized that local recurrences are not translatable to worse survival when acted on properly and at an early stage. Thus, endoscopy must have intensive mandatory follow-up, which in and of itself may negatively impact quality of life. Currently, there is room for improvement with regards to kidney sparing surgery: (i) optimizing clinical risk stratification, (ii) improving tumor detection, (iii) improving means of tumor grading, and (iv) preventing tumor recurrences. There are several urinary markers available to perhaps assist with the above, including:

  • Epigenetic, DNA methylation, panels of urothelial specific methylation biomarkers
  • Bladder Tumor Antigen: detects human complement factor H-related protein
  • Nuclear Matrix Protein 22: detection of protein level of nucleus mitotic apparatus
  • Immunocyt: detects monoclonal antibodies directed against 3 specific antigens

EpiCheck performance is much better for upper tract tumor samples compared to bladder cancer samples. The sensitivity is 83%, specificity is 81%, positive predictive value is 85%, negative predictive value is 78%, and accuracy is 82%. BladderCARE is associated with a sensitivity of 96%, specificity of 88%, positive predictive value of 89%, negative predictive value of 96%, and accuracy of 92%. For low grade tumors, BladderCARE sensitivity is 89% compared to 0% for cytology, whereas for high grade disease, sensitivity is 97.5% compared to 43% for cytology.

With regards to intravesical recurrence after endoscopy, single center retrospective studies, which have to date been small and prone to selection bias, suggest a recurrence risk of 14-68%. The EAU guidelines are somewhat lukewarm on this subject noting “While there is no direct evidence supporting the use of intravesical instillation of chemotherapy after kidney-sparing surgery, single-dose chemotherapy may be effective in this setting (level of evidence: 4).” Dr. Baard highlighted that in early 2023 she and colleagues started the SINCERE Registry, a prospective, multicenter study to test the effect of a single instillation of mitomycin C on intravesical recurrence rate after ureteroscopy for primary upper tract urothelial carcinoma.

For endocavitary treatment of Ta/T1 disease, Dr. Baard notes that upper tract recurrence rates are 40%, cancer specific survival is 94%, and overall survival is 71%. However, previous small studies have shown no difference in regimens/instillation approach, and upper tract recurrence rates are comparable to nontreated patients. Dr. Baard then discussed the OLYMPUS trial,1 which was an open-label, single-arm, phase 3 trial of primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel. Enrolled patients received six once-weekly instillations of UGN-101 as an induction course, which was administered via retrograde instillation with ureteral catheterization. Of the 71 patients who received at least one dose of treatment, 42 patients (59%, 95% CI 47-71%) had a complete response at the time of primary disease evaluation. Of the remainder, 8 (11%) had a partial response, 12 (17%) had no response, 6 (8%) had newly diagnosed high-grade disease, and 3 (4%) had an indeterminate response. Despite these promising results, toxicity was not insignificant: 67 patients (94%) experienced adverse events and 26 (37%) patients experienced severe adverse events. 60 patients (85%) had adverse events which were deemed treatment-related and 19 (27%) had severe treatment related events. 19 patients (27%) discontinued treatment due to adverse events both in the initial 6-week treatment period (9 patients, 13%) and during maintenance (10 patients, 14%). Among adverse events of particular interest, renal functional impairment was noted in 14 patients (20%). There was also a significant burden of urinary tract morbidity: among 71 patients who received at least one dose of study medication, 48 patients (68%) had an adverse event related to the urinary system including 11 (23%) who did not require surgical intervention, 24 (50%) who required transient stent placement, 11 (23%) who required long-term stent placement (still in place at the time of data cut-off), and 2 (4%) who required nephroureterectomy due the need for permanent drainage as a result of ureteral stenosis.

A recently published study in early 2023 by Labbate and colleagues2 assessed real world evidence of UGN-101 as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma. Among 15 high volume centers, adjuvant UGN-101 was used in 52 of 115 (45%) renal units, and at first endoscopic evaluation 36/52 (69%) were without visible disease. At a median follow-up of 6.8 months, the ipsilateral disease-free rate was 63%, and recurrence after adjuvant UGN-101 was more likely in multifocal tumors compared to unifocal (HR 3.3, 95% CI 1.07-9.91). Compared with UGN-101 treatment for chemoablation of measurable disease, there were significantly fewer disease detections with adjuvant therapy (p < 0.001), and ureteral stenosis after UGN-101 was diagnosed in only 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy (p = 0.28).

Dr. Baard concluded her presentation discussing improvement in technologies and drugs to support kidney sparing surgery with the following take-home messages:

  • Kidney sparing surgery should include tailored treatment in selected patients to preserve renal units
  • Intensive follow-up is mandatory due to recurrence risk, intravesical recurrences, and disease upgrading
  • We need to continue exploring the use of urinary markers, as well as the use of adjuvant bladder- and endocavitary instillations

Presented by: Joyce Baard, MD, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 European Association of Urology (EAU) Annual Meeting, Milan, IT, Fri, Mar 10 – Mon, Mar 13, 2023. 


  1. Kleinmann N, Matin SF, Pierorazio PM, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): An open-label, single-arm, phase 3 trial. Lancet Oncol 2020 Jun;21(6):776-785.
  2. Labbate C, Woldu S, Murray K, et al. Efficacy and safety of Mitomycin Gel (UGN-101) as an adjuvant therapy after complete endoscopic management of upper tract urothelial carcinoma. J Urol. 2023 Jan 19 [Epub ahead of print].