The role of histological subtype and chemotherapy on prognosis of ureteral cancer.

OBJECTIVE: To date, there have been few studies examining the prognostic implications of histological subtypes in ureteral cancer. And chemotherapy plays a crucial role in the treatment of ureteral cancer, while many factors influence the efficacy of chemotherapy. This study aimed to utilize the Surveillance, Epidemiology and End Results database to assess the impact of histological type on ureteral cancer prognostic outcomes and discovered how histological type and T-stage influence the efficacy of chemotherapy. METHODS: Based on Surveillance, Epidemiology, and End Results Program, we reviewed 8915 records of patients with primary ureteral cancer from 18 centers between 2000 and 2018. We focused on the overall survival and cancer-specific survival of the records and used Kaplan‒Meier method to calculate survival curves. RESULTS: In the comparison of prognostic outcomes, atypical subtypes exhibited a less favorable prognosis compared to typical ureteral carcinoma. Notably, patients diagnosed with papillary urothelial carcinoma demonstrated the most favorable overall survival (p = 0.005). Statistically significant benefits were observed in the prognosis of patients with non-papillary urothelial carcinoma who received chemotherapy (HR = 0.860, 95% CI 0.764-0.966, p = 0.011), while chemotherapy did not yield a statistically significant effect on the prognosis of patients with papillary urothelial carcinoma (HR = 1.055, 95% CI 0.906-1.228, p = 0.493). Chemotherapy had an adverse impact on the prognosis of patients with T1 ureteral cancer (HR = 1.235, 95% CI 1.016-1.502, p = 0.034), whereas it exhibited a positive prognostic effect for T3/T4 cases (HR = 0.739, 95% CI 0.654-0.835, p < 0.001). CONCLUSIONS: Histological type affects the prognosis of ureteral cancer. And evaluation of cancer histological type and T stage in ureteral cancer patients prior to chemotherapy is mandatory.

Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

Sequential endoluminal gemcitabine and docetaxel for the treatment of clinically non-invasive high-grade upper tract urothelial carcinoma.

PURPOSE: There is an unmet need for effective renal sparing treatments for upper tract urothelial carcinoma (UTUC). Gemcitabine/Docetaxel (Gem/Doce) has shown favorable efficacy in nonmuscle invasive bladder cancer. We report the outcomes of patients treated with endoluminal Gem/Doce for noninvasive high-grade UTUC. METHODS: A retrospective review of patients treated with Gem/Doce for clinically noninvasive high-grade UTUC with no radiographic or endoscopically visible disease, either at diagnosis or following ablation, was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. Induction instillations were performed weekly for 6 weeks, followed by 6 monthly instillations if disease-free. Recurrence was defined as biopsy-proven disease or high-grade (HG) cytology. Progression was defined by development of muscle invasion, metastases, or death due to cancer. Survival was assessed with the Kaplan-Meier method. RESULTS: The final cohort included 31 patients with 41 upper tract units, 51% of which would have been dialysis dependent with nephroureterectomy. Median (IQR) age was 74 years (68-81). Median follow-up was 29 months (IQR 20-58). Prior to treatment, 37 (90%) units presented with a localizing HG cytology (presumed occult CIS), and 4 (9.8%) with HG biopsy-proven disease. Sixteen (52%) patients reported any side effects; 5 were Grade 3 and 1 was Grade 5. Recurrence-free survival was 76%, 54%, and 40% at 1, 2, and 3 years, respectively. Five patients died from urothelial carcinoma. The 3-year progression-free and overall survival were 75% and 75%, respectively. CONCLUSIONS: Gem/Doce demonstrates promising safety and efficacy as a renal-sparing treatment option for high-grade UTUC in appropriately selected patients.

Successful Kidney-Sparing Systemic Therapy for a High-Risk Ureteral Carcinoma Case.

Upper tract urothelial carcinoma (UTUC) refers to the malignancies located from renal calices toward the end of the ureter and could be classified as renal pelvis carcinoma and ureteral carcinoma. For high-risk UTUC cases with a normal contralateral kidney, radical nephroureterectomy is the standard treatment. As for low-risk UTUC cases or solitary kidney cases, kidney-sparing therapy may be a better choice. Besides, to prevent postoperative recurrence, systemic therapy should be applied, though the investigation is still ongoing. In this case report, we reported a rare case diagnosed with high-risk ureteral carcinoma, but he underwent kidney-sparing therapy due to chronic kidney disease. Recurrence has occurred after segmental ureterectomy. But through the utilization of ablation, bladder instillation, and tislelizumab, endoscopy and CT were normal in the follow-up (the patient refused to take washings from the upper urinary tract) for more than a year. In all, the utilization of ureteroscopic retrograde tumor ablation, BCG bladder instillation, and tislelizumab injection to treat high-risk ureteral carcinoma for kidney-sparing therapy have filled in the gap in this field, which should be promoted to help more patients in similar situations.

Design and rationale of a single-arm phase II study of neoadjuvant Durvalumab and Gemcitabine associated with Cisplatin or Carboplatin for upper urinary tract urothelial cancer: the iNDUCT trial (NCT04617756).

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer. STUDY DESIGN AND ENDPOINTS: Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned. PATIENTS AND INTERVENTIONS: Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee.

Comparison of neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma in real-world practice: a multicenter retrospective study.

BACKGROUND: Multiple studies have demonstrated the effectiveness of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with upper tract urothelial carcinoma compared with surgery alone. However, no clinical trial has established the superiority of neoadjuvant chemotherapy or adjuvant chemotherapy in terms of perioperative outcomes. METHODS: We conducted a retrospective analysis encompassing 164 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy and received perioperative chemotherapy. Of these patients, 65 (39.6%) and 99 (60.4%) received neoadjuvant chemotherapy and adjuvant chemotherapy, respectively. Recurrence-free survival and cancer-specific survival were computed using the Kaplan-Meier method. Additionally, we conducted Cox regression analyses to evaluate the risk factors for recurrence-free survival and cancer-specific survival. RESULTS: Pathological downstaging was seen in 37% of the neoadjuvant chemotherapy group. However, no pathological complete response was observed in this cohort. The Kaplan-Meier curves demonstrated significantly lower recurrence-free survival and cancer-specific survival in patients who received adjuvant chemotherapy. Multivariate Cox regression analysis revealed patients treated with adjuvant chemotherapy exhibited a marked association with inferior recurrence-free survival and cancer-specific survival. CONCLUSION: Our study has suggested that neoadjuvant chemotherapy would be more effective in high-risk upper tract urothelial carcinoma patients compared with adjuvant chemotherapy.

Postoperative adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) who underwent kidney-sparing surgery (KSS): a single-center study.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of postoperative adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) who underwent kidney-sparing surgery (KSS). METHODS: We retrospectively reviewed the clinical records of 31 patients with primary UTUC who underwent kidney-sparing surgery (KSS) and who were treated with adjuvant radiotherapy at our center between October 1998 and May 2017. Statistical analyses were performed with SPSS 23.0. The primary endpoints of this study included overall survival (OS) and local recurrence-free survival (LRFS); the secondary endpoints were disease-free survival (DFS) and treatment-related toxicity. RESULTS: The median follow-up was 58.4 months (range, 12.7-185.3 months), and the median local recurrence time was 59.0 months (range, 7.0-185 months). All of the patients completed radiotherapy on schedule, and no grade 3-4 late-stage reaction was observed. The estimated 5-year and 10-year OS, DFS and LRFS rates of the patients were 64.0%, 61.1%, 69.6% and 48.0%, 40.9%, 64.6%, respectively. Univariate analysis showed that age (χ2 = 4.224, P = 0.040), R0 resection (χ2 = 3.949, P = 0.047), and early stage (I + II) (χ2 = 6.515, P = 0.011) were associated with good OS; DFS benefit in early stage patients (χ2 = 6.151, P = 0.013) and age<70 years old (χ2 = 5.091, P = 0.024). Patients with distal ureteral segments had better LRFS than patients with proximal ureteral cancer (χ2 = 5.248, P = 0.022). However, multivariate analysis showed that age was the only factor of OS (χ2 = 4.099, P = 0.043). CONCLUSION: Adjuvant radiotherapy is safe and tolerated, and LRFS was superior in middle and distal ureteral cancer than in proximal ureteral cancer.

[Preoperative chemotherapy for patients with upper tract urothelial carcinoma: Impact on renal function]. / Chimiothérapie préopératoire des tumeurs des voies excrétrices supérieures : impact sur la fonction rénale.

PURPOSE: Upper tract urothelial carcinoma (UTUC) are rare tumors with a poor prognosis. The standard treatment for localized disease is based on total nephroureterectomy (NUT) followed by platinum-based adjuvant chemotherapy for eligible patients at risk of recurrence. However, many patients have renal failure after surgery preventing chemotherapy. Thus, the place of preoperative chemotherapy (POC) is questioned with little information available about renal toxicity and efficacity. METHODS: A single center retrospective study was performed on patients with UTUC who received POC. RESULTS: In all, 24 patients with localized UTUC were treated with POC between 2013 and 2022. Twenty-one (91%) had secondarily NUT. In this cohort, POC did not result in degradation of median renal function (pre-POC median GFR: 70mL/min, post-POC median GFR: 77mL/min, P=0.79), unlike NUT (post-NUT median GFR: 51.5mL/min, P<0.001). In addition, the rate of complete pathological response to pathological examination was 29%. After a median follow-up of 27.4 months, the overall survival rate was 74% and the recurrence-free survival rate was 46%. CONCLUSION: POC for UTUC shows a very reassuring renal toxicity profile and encouraging histological results. These data encourage prospective studies assessing its place for UTUC management.

The efficacy and timing of adjuvant chemotherapy in upper tract urothelial carcinoma.

BACKGROUND: A recovery period between surgery and initiation of adjuvant chemotherapy (AC) is common in patients with upper tract urothelial carcinoma (UTUC), which can progress after a relatively long time. Therefore, the efficacy of AC initiated within 90 days after radical nephroureterectomy (RNU) was evaluated in UTUC patients at stage ≥pT2 (N0-3M0), in addition to the effect of delayed AC initiation on survival outcomes. METHODS: Clinical data for 428 UTUC patients diagnosed with transitional cell carcinoma with postoperatively confirmed pathological stages, muscle-invasive or greater-stage (pT2-4) disease, any nodal status, and metastasis-free (M0) disease were retrospectively analyzed. All patients who received AC were treated within 90 days after RNU and underwent at least 4 cycles of the AC procedure. Then, patients receiving AC were divided into the "within 45 days" and "45 to 90 days" groups according to the time interval between RNU and AC initiation. Their clinicopathological characteristics were evaluated and the survival outcomes of the 2 groups were compared. Any adverse events that occurred during the AC process were also recorded. RESULTS: A total of 428 patients were analyzed in the study, including 132 individuals who underwent the AC procedure with platinum in combination with gemcitabine within 90 days after RNU and 296 patients who failed to initiate AC within 90 days. The median age of all patients was 68 years (mean 67, range 28-90 years), and the median follow-up was 25 months (mean 36, range 1-129 months). There were no significant differences in age, sex, lymph node metastasis, tumor location, hydronephrosis status, hematuria status, cancer grade, or multifocality between the 2 groups. Individuals undergoing AC initiated within 90 days of RNU showed a significantly decreased mortality relative to those patients who did not receive AC. Shorter intervals between RNU and AC initiation within 45 days vs. 45-90 days did not improve patient OS and cancer-specific survival (CSS) and may have increased the incidence of adverse events. CONCLUSION: The present study data supported the finding that a platinum-based combination with gemcitabine regimen initiated postoperatively significantly improved OS and CSS in patients with UTUC at stages ≥pT2 (N0-3M0). Furthermore, no survival benefit was evident in patients who started AC within 45 days after RNU compared to those who received AC within 45 to 90 days.

Intracavitary Chemotherapy after kidney-Sparing Therapy for Upper Tract Urothelial Carcinoma: A Meta-Analysis.

PURPOSE: Intracavitary chemotherapy is one of the current treatment options for kidney-sparing treatment of upper tract urothelial carcinoma (UTUC). The purpose of this meta-analysis was to assess the efficacy and safety of intracavitary perfusion. METHODS: We carefully selected publications for study from four databases (Embase, PubMed, Web of Science, and Scopus) up to January 2023. The R 4.0.4 software was used to calculate the pooled ratio and its 95% confidence intervals (95% CIs). The I2 score was used to test heterogeneity, and the funnel plot was used to estimate the publication bias. RESULTS: Thirty-four studies with a total of 788 patients were included in this study. The overall survival at a median follow-up of 26.3 months was 87.2% (95% CI 0.80-0.93). The cancer-specific survival at a median follow-up of 30 months was 94.1% (95% CI 0.89-0.98). At a median follow-up of 30 months, the recurrence rate of UTUC was 27.5% (95% CI 0.21-0.34). By subgroup analysis, we found that the recurrence rate in patients with T1 / Ta stage was 35.1% and CIS stage 29.0%. The recurrence rates of BCG, Mitomycin C, and Mitomycin Gel (UGN101) were 31.2%, 41.3% and 12.9%, respectively. The recurrence rates for anterograde and retrograde perfusion were 28.5% and 21.8%, respectively. CONCLUSION: With the advent of new drugs, including UGN101, patients with UTUC have a better prognosis. Therefore, kidney preservation therapy for patients with UTUC would be promising.

The ablative effect of mitomycin reverse thermal gel: Expanding the role for nephron preservation therapy in low grade upper tract urothelial carcinoma.

PURPOSE: Assess the real-world ablative effect of mitomycin reverse thermal gel for low-grade upper tract urothelial carcinoma (UTUC) in patients who undergo biopsy only or partial ablation and evaluate utility of complete ablation prior to UGN-101. MATERIAL AND METHODS: We retrospectively reviewed low-grade UTUC patients treated with UGN-101 from 15 high-volume centers. Patients were categorized based on initial endoscopic ablation (biopsy only, partial ablation, or complete ablation) and by size of remaining tumor (complete ablation, <1cm, 1-3cm, or >3cm) prior to UGN-101. The primary outcome was rendered disease free (RDF) rate at first post-UGN-101 ureteroscopy (URS), defined as complete response or partial response with minimal mechanical ablation to endoscopically clear the upper tract of visible disease. RESULTS: One hundred and sixteen patients were included for analysis after excluding those with high-grade disease. At first post-UGN-101 URS, there were no differences in RDF rates between those who at initial URS (pre-UGN-101) had complete ablation (RDF 77.0%), partial ablation (RDF 55.9%) or biopsy only (RDF 66.7%) (P = 0.14). Similarly, a complimentary analysis focusing on tumor size (completely ablated, <1cm, 1-3cm or >3cm) prior to UGN-101 induction did not demonstrate significant differences in RDF rates (P = 0.17). CONCLUSION: The results of the early real-world experience suggest that UGN-101 may play a role in initial chemo-ablative cytoreduction of larger volume low-grade tumors that may not initially appear to be amenable to renal preservation. Further studies will help to better quantify the chemo-ablative effect and to identify clinical factors for patient selection.

Promising Response of Paclitaxel in Metastatic Transitional Cell Carcinoma of Distal Ureter Complicated with Hydroureteronephrosis: A Case Report.

Ureteric carcinoma is the rarest of all urothelial malignancies, and little attention has been given to it. Palliation in these groups of patients is a dilemma in the clinics. Use of chemotherapeutic agents in ureteric carcinoma is a double edged sword, as these patients had already impaired renal function due to post-renal failure and nephrotoxic nature of most of the chemotherapeutic agents can further deteriorate the renal function, making the management approach, a relatively visionary task. Here, we present a case of a 77-year-old female with metastatic ureteric carcinoma locally complicated with hydroureteronephrosis, coming to us with gross haematuria, lower abdominal pain along with cough. Apart from age factor of the lady, presence of hydroureteronephrosis and pulmonary metastases was another challenge for us. Paclitaxel remains the mainstay of our treatment. Keywords: carcinoma; case reports; metastasis; paclitaxel.

The role of perioperative chemotherapy for upper tract urothelial carcinoma patients treated with radical nephroureterectomy.

PURPOSE: To summarize evidence regarding the use of neoadjuvant (NAC) and adjuvant chemotherapy (AC) among patients treated with radical nephroureterectomy (RNU). METHODS: A comprehensive literature search of PubMed (MEDLINE), EMBASE and the Cochrane library was performed to identify any original or review article on the role of perioperative chemotherapy for UTUC patients treated with RNU. RESULTS: With regards to NAC, retrospective studies consistently suggested that it may be associated with better pathological downstaging (pDS) ranging from 10.8 to 80% and complete response (pCR) ranging from 4.3 to 15%, while decreasing the risk of recurrence and death as compared to RNU alone. Even higher pDS ranging from 58 to 75% and pCR ranging from 14 to 38% were observed in single-arm phase II trials. With regards to AC, retrospective studies provided conflicting results although the largest report from the National Cancer Database suggested an overall survival benefit in pT3-T4 and/or pN + patients. In addition, a phase III randomized controlled trial showed that the use of AC was associated with a disease-free survival benefit (HR = 0.45; 95% CI = [0.30-0.68]; p = 0.0001) in pT2-T4 and/or pN + patients with acceptable toxicity profile. This benefit was consistent in all subgroups analyzed. CONCLUSIONS: Perioperative chemotherapy improves oncological outcomes associated with RNU. Given the impact of RNU on renal function, the rational is stronger for the use of NAC which impacts final pathology and potentially prolongs survival. However, the level of evidence is stronger for the use of AC that has been proven to decrease the risk of recurrence after RNU with a potential survival benefit.

Effect of Adjuvant Systemic Chemotherapy on Intravesical Recurrence After Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma.

BACKGROUND/AIM: There are few reports confirming the relationship between the therapeutic effects of adjuvant systemic chemotherapy and intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. We aimed to evaluate the benefits of adjuvant systemic chemotherapy on intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 133 patients with pathological T stage ≥3 upper urinary tract urothelial carcinoma or lymph node metastasis who underwent radical nephroureterectomy between January 2010 and September 2020 at our hospital and other satellite hospitals. In total, 60 patients received adjuvant systemic chemotherapy, and 73 did not. The Student's t-test and chi-square (χ2) test were used to compare between-group differences. The log-rank test was utilized to compare differences in intravesical recurrence between patients with or without adjuvant systemic chemotherapy. Cox proportional hazards regression analysis was performed to identify the predictive factors of intravesical recurrence. RESULTS: The median follow-up period was 25 months. Forty (30.1%) patients presented with intravesical recurrence. The 1-year intravesical recurrence-free survival rates of patients with and without adjuvant systemic chemotherapy were 86.0% and 70.2%, respectively (p=0.046). Multivariate analysis showed that adjuvant systemic chemotherapy was significantly associated with a lower risk of intravesical recurrence (p=0.032). CONCLUSION: Patients with pathological T stage ≥3 upper urinary tract urothelial carcinoma or lymph node metastasis can have a satisfactory intravesical recurrence-free survival rate with adjuvant systemic chemotherapy.

Prognostic nomogram for overall survival in upper urinary tract urothelial carcinoma (UTUC) patients treated with chemotherapy: a SEER-based retrospective cohort study.

OBJECTIVE: To establish a prognostic nomogram among UTUC patients who received chemotherapy. METHODS: 1195 UTUC patients who received chemotherapy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for the period between 2004 and 2015. Patients were randomly divided into a training and a validation set. Nomogram was constructed to predict 1-, 3-, and 5-year overall survival (OS) in those patients. Receiver-operating characteristic curves (ROCs), calibration plots, and Decision curve analysis (DCA) were applied to assess and compare the discrimination, accuracy, and practicability of the nomogram with 8th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system. RESULTS: Six clinical parameters were identified as independent prognostic factors for UTUC patients' OS, including age, marital status, TNM stage, and surgical methods of the primary site. The ROC curves showed a satisfactory discrimination capacity of the nomogram, with 1-, 3-, and 5-year area under curve (AUC) values of 0.789, 0.772, and 0.763 in the training set and 0.772, 0.822, and 0.814 in the validation set, respectively. Calibration curves indicated a good agreement between actual observation and nomogram prediction. ROC and DCA curves showed our nomograms exhibited larger benefits than the 8th AJCC-TNM staging system. CONCLUSIONS: A prognostic nomogram was established and validated to present individual predictions of OS among chemotherapeutic UTUC patients. This nomogram may assist clinicians in accurate survival prognostication, treatment decision-making, and design of future clinical trials.

Efficacy and Safety of Mitomycin Gel (UGN-101) as an Adjuvant Therapy After Complete Endoscopic Management of Upper Tract Urothelial Carcinoma.

PURPOSE: We describe a novel application of the reverse thermal polymer gel of mitomycin C (UGN-101) as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients treated with UGN-101 from 15 high-volume centers. Adjuvant therapy was defined as treatment administered following visually complete endoscopic ablation. Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. Ipsilateral disease-free and progression-free survival were estimated by the Kaplan-Meier method. Ureteral stenosis and other adverse events were abstracted from the medical records. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy. RESULTS: Adjuvant UGN-101 after complete endoscopic ablation was used in 52 of 115 (45%) renal units in the oncologic analysis. At first endoscopic evaluation, 36/52 (69%) were without visible disease. At 6.8 months' median follow-up, the ipsilateral disease-free rate was 63%. Recurrence after adjuvant UGN-101 therapy 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 < .001). Ureteral stenosis after UGN-101 was diagnosed in 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy (P = .28). CONCLUSIONS: In patients being considered for UGN-101, maximal endoscopic ablation prior to UGN-101 treatment may result in fewer patients with disease at first endoscopy and possibly fewer adverse events than primary chemoablative therapy. Longer follow-up is needed to determine if UGN-101 after complete endoscopic ablation will lead to durable disease-free interval.

Antegrade administration of mitomycin gel for upper tract urothelial carcinoma via percutaneous nephrostomy tube: a multi-institutional retrospective cohort study.

OBJECTIVES: To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy. PATIENTS AND METHODS: Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. RESULTS: Thirty-two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow-up of 13.0 months post induction. CONCLUSIONS: Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.

Practice trends for perioperative intravesical chemotherapy in upper tract urothelial carcinoma: Low but increasing utilization during minimally invasive nephroureterectomy.

INTRODUCTION: Perioperative intravesical chemotherapy (IVC) at or around the time of radical nephroureterectomy (RNU) reduces the risk of intravesical recurrence. Guidelines since 2013 have recommended its use. The objective of this study is to examine IVC utilization and determine predictors of its administration within a large international consortium. METHODS AND MATERIALS: Data was collected from 17 academic centers on patients who underwent robotic/laparoscopic RNU between 2006 and 2020. Patients who underwent concomitant radical cystectomy and cases in which IVC administration details were unknown were excluded. Univariate and multivariate analyses were utilized to determine predictors of IVC administration. A Joinpoint regression was performed to evaluate utilization by year. RESULTS: Six hundred and fifty-nine patients were included. A total of 512 (78%) did not receive IVC while 147 (22%) did. Non-IVC patients were older (P < 0.001), had higher ECOG scores (P = 0.003), and had more multifocal disease (23% vs. 12%, P = 0.005). Those in the IVC group were more likely to have higher clinical T stage disease (P = 0.008), undergone laparoscopic RNU (83% vs. 68%, P < 0.001), undergone endoscopic management of the bladder cuff (20% vs. 4%, P = 0.008). Multivariable regression showed that decreased age (OR 0.940, P < 0.001), laparoscopic approach (OR 2.403, P = 0.008), and endoscopic management of the bladder cuff (OR 7.619, P < 0.001) were significant predictors favoring IVC administration. Treatment at a European center was associated with lower IVC use (OR 0.278, P = 0.018). Overall utilization of IVC after the 2013 European Association of Urology (EAU) guideline was 24% vs. 0% prior to 2013 (P < 0.001). Limitations include limited data regarding IVC timing/agent and inclusion of minimally invasive RNU patients only. CONCLUSIONS: While IVC use has increased since being added to the EAU UTUC guidelines, its use remains low at academic centers, particularly within Europe.

Longitudinal GFR trends after neoadjuvant chemotherapy prior to nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: Renal function dictates sequencing and eligibility for definitive therapy in upper tract urothelial carcinoma. We investigated longitudinal glomerular filtration rate (GFR) changes after neoadjuvant chemotherapy (NAC) and nephroureterectomy (RNU). MATERIALS AND METHODS: Patients treated with ≥3 cycles of chemotherapy prior to RNU for UTUC from 2000 to 2019 were included. GFR was calculated by CKD-Epi before chemotherapy, before RNU, 1 to 3 months, and 12 months post-RNU. Pathologic stage and overall survival were compared in those with stable GFR (+/-10% of baseline) to the rest of the cohort. RESULTS: One hundred and fifty-two patients received ≥3 cycles of NAC, with 121 (79%) receiving at least 1 cycle of cisplatin. Renal function dropped by mean of 22.3 ml/min/1.73 m2 from the beginning of chemotherapy to 1-year post-surgery. In patients receiving cisplatin, a mean decline of 26.2 ml/min/1.73 m2 was observed vs. 8.8 ml/min/1.73 m2 without cisplatin-based NAC (P < 0.01). GFR after RNU was unchanged between 3 and 12 months postoperatively. At 1 to 3 months after RNU, 19% of patients had GFR<30 ml/min/1.73m2. Improvement in GFR during NAC was associated with invasive final pathologic stage (P = 0.018) and worse overall survival (P = 0.049). CONCLUSIONS: In patients managed with NAC prior to RNU, renal function stabilizes at 1 to 3 months post-operatively and remains clinically similar for cisplatin or non-cisplatin-based therapy. Improvement in GFR during NAC was associated with higher pathologic stage and poorer survival, especially in those receiving non-cisplatin-based therapy, an observation that requires further investigation.