Nephroureterectomy Research Articles

Ideal cystoscopic interval after nephroureterectomy in patients with upper tract urothelial carcinoma.

The purpose of this study was to clarify the appropriate cystoscopic interval after nephroureterectomy (NU) for upper tract urothelial carcinoma (UTUC) using a hypothetical model. A total of 155 patients who underwent NU in 15 years were retrospectively evaluated. Three hypothetical models for surveillance intervals were created: 3 (model 1), 6 (model 2) and 12 months (model 3). We superimposed these models on the actual surveillance of each patient and analyzed the observed timing of recurrence. The time from recurrence to scheduled cystoscopy (timeRCS) was defined as the time from recurrence to estimated cystoscopy. The gap risk ratio was calculated based on the average of timeRCS for model 1 at 0-1 year after surgery. The median follow-up was 20.5 months. Intravesical recurrence was observed in 63 patients (40.6%). The 3-year intravesical recurrence-free survival rate in patients without a history of bladder cancer before NU was significantly higher than in those with a history of bladder cancer (61% vs. 42%, P = 0.034). The medians of timeRCS for models 1, 2, and 3 were 1.9, 2.9, and 8.4 months, respectively. The gap risk ratios for model 1 at 1-3 years, model 2 at 2-3 years for patients with a history of bladder cancer, and model 2 at 1-3 years for patients without a history of bladder cancer were less than 1.0. Model analysis shows that the cystoscopic follow-up interval can be extended depending on the presence or absence of a history of bladder cancer and the time after NU.

ASO Visual Abstract: Open Versus Minimally Invasive Nephroureterectomy: Contemporary Analysis from a Wide National Population-Based Database.

Contemporary trend analysis of a large national data set confirms the occurrence of a significant shift toward minimally invasive nephroureterectomy (MINU), which is gradually replacing open nephroureterectomy (ONU). A minimally invasive approach is associated with a lower risk of complications. Social determinants of health (SDOH) are non-clinical factors that ultimately may have an impact on the outcomes of the nephroureterectomy (NU) procedure ( https://doi.org/10.1245/s10434-024-15565-6 ).

Perioperative management of upper tract urothelial carcinoma in the Nordic countries

BackgroundUpper tract urothelial carcinoma (UTUC) is a rare malignancy, with typically only few new cases annually per urological department. Adherence to European association of urology (EAU) guidelines on UTUC in the Nordic countries is unknown. The objective of this survey was to examine the implementation of EAU guidelines, the perioperative management and organization of the treatment of UTUC in the Nordic countries.MethodsThe electronic survey was distributed to 93 hospitals in the Nordic countries performing radical nephroureterectomy (NU). The survey consisted of 57 main questions and data was collected between December 1st, 2021 and April 23rd, 2022.ResultsOverall response rate was 47/93 (67%) with a completion rate of 98%. Five out of the 6 examined subjects on diagnostic practice are applied by ≥ 72% of the participating centers. NU as treatment for high-risk UTUC is performed by 37/47 (79%), and 91% include a bladder cuff excision.ConclusionsAdherence to EAU guidelines is high on diagnostic practice in the Nordic countries, whereas disease management is less coherent.

Survival benefit of nephroureterectomy in systemic therapy exposed metastatic upper tract urinary urothelial carcinoma patients.

It is unknown whether the stage of the primary may influence the survival (OS) of metastatic upper tract urothelial carcinoma (mUTUC) patients treated with nephroureterectomy (NU) and systemic therapy (ST). We tested this hypothesis within a large-scale North American cohort. Within Surveillance Epidemiology and End Results database 2000-2020, all mUTUC patients treated with ST+NU or with ST alone were identified. Kaplan-Maier plots depicted OS. Multivariable Cox regression (MCR) models tested for differences between ST+NU and ST alone predicting overall mortality (OM). All analyses were performed in localized (T1-T2) and then repeated in locally advanced (T3-T4) patients. Of all 728 mUTUC patients, 187 (26%) harbored T1-T2 vs 541 (74%) harbored T3-T4. In T1-T2 patients, the median OS was 20months in ST+NU vs 10months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU independently predicted lower OM (HR 0.37, p < 0.001). Conversely, in T3-T4 patients, the median OS was 12 in ST+NU vs 10months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU was not independently associated with lower OM (HR 0.85, p = 0.1). In mUTUC patients, treated with ST, NU drastically improved survival in T1-T2 patients, even after strict methodological adjustments (multivariable and landmark analyses). However, this survival benefit did not apply to patients with locally more advanced disease (T3-T4).

Immune checkpoint inhibitors in high-grade upper tract urothelial carcinoma: Paradigm shift emphasizing organ preservation.

The aim was to evaluate the role of immune check point inhibitors (ICIs) in patients with high-grade upper tract urothelial carcinoma (UTUC) who are managed endoscopically when nephroureterectomy (NU) is not feasible, such as in patients who are either not candidates for NU or decline extirpative surgery. All patients diagnosed with high-grade UTUC and managed endoscopically between January 1996 and August 2022 were included in the study. Subsequently, patients were categorised based on their use of ICIs into group 1 (patients who did not receive ICIs) and group 2 (patients who received ICIs). Survival outcomes were assessed using Kaplan-Meier analysis, while a multivariable regression model was employed to analyse the impact of clinical characteristics on survival. A total of 29 patients were enrolled, with 14 in group 1 and 15 in group 2. Both groups exhibited similar demographic and disease characteristics, including multifocality, laterality and initial tumour size. The median follow-up period was 29.2months. Notably, group 2 demonstrated significantly enhanced overall and metastasis-free survival rates compared to group 1. At 47.8months, the overall survival rate was 0% (all patients died) in group 1, whereas it was 85.7% in group 2. Similarly, the metastasis-free survival rate was 0% (all patients had metastatic disease) in group 1 at 40.6months, whereas it reached 78.0% in group 2. The multivariable analysis indicated a correlation between ICI usage and improved survival outcomes, with a hazard ratio of 0.002. Utilisation of adjuvant ICIs in the setting of endoscopically treated patients with high-grade UTUC is associated with significantly improved survival rates. ICIs should be considered in this patient population, however, more studies with larger sample size are warranted.

Neoadjuvant nivolumab (N) + ipilimumab (I) in cisplatin-ineligible patients with upper tract urothelial cancer (UTUC): Updated results.

645 Background: Perioperative platinum-based chemotherapy for UTUC improves pathologic responses and disease-free survival (DFS). We report the updated results from our on-going phase II neoadjuvant trial of N+I for cisplatin-ineligible patients (pts) with UTUC (NCT03520491). Methods: Cisplatin-ineligible pts with histologically confirmed high-grade UTUC and/or radiographically invasive UTUC with positive selective urine cytology were eligible. Pts were treated with I 3mg/kg + N 1mg/kg (weeks 0, 6), and “N” 3mg/kg (week 3) prior to radical nephroureterectomy (NU). The primary endpoint (EP) was pathologic complete response (pCR, ypT0pN0) and secondary EPs included &lt;ypT2pN0 rate, DFS, and toxicity. Next generation sequencing of pre-treatment tumors was correlated with pathologic response. Results: Seventeen pts (76% male) were enrolled between 2/2021-6/2023 with median age 73 (range 59-85). Primary sites included ureter in 10 pts, renal pelvis in 5 and both in 2. Median tumor diameter was 3.0 cm, (range: 1.5 - 4.2 cm), with 8 pts (47%) having hydronephrosis. To date, 11 pts (65%) have received all planned treatment, 6 pts had N+/-I stopped early due to treatment-related toxicities, 2 pts are pending NU, 13 pts have undergone NU, 1 declined surgery, and another progressed on N+I. A pCR was seen in 4/15 pts (27%) and &lt;ypT2pN0 in 9/15 (60%). Median time from last treatment to NU was 1.6 months (range 0.5-4.9). Three pts developed metastatic recurrence at 3.9, 10.3 and 15.6 months after treatment initiation. CTCAE grade ≥3 treatment-related adverse events occurred in 5 pts (29%). Four pts died during follow up: two of metastatic disease, one of complications related to a bowel leak (7.2 months after N+I initiation and 4.7 months after NU), and one from complications of a fall unrelated to disease or treatment (9.2 months after N+I initiation and 4.7 months after NU). Median tumor mutational burden (TMB) in 9 pts with pre-treatment sequencing was 13.2 mutations/mb (range 4.1-106.3), with 4/5 pts with TMB&gt;10 &lt;ypT2pN0 at NU. Pathogenic germline variants in mismatch repair genes were confirmed in 4 pts (MSH2 in 3, MLH1 in 1) and MSI-high tumors without germline alterations in 2 pts, with 5 of 6 completing NU (1 pending surgery); all 5 achieved pCR (n=3) or ypTaN0 (n=2) and remain alive and disease-free at last follow-up (6, 13.4, 17, 17.9 and 31 months). Conclusions: Updated findings from an on-going phase II trial of cisplatin-ineligible pts with UTUC receiving neoadjuvant N+I shows clinical activity in line with our initial results. All pts with pathogenic germline variants in mismatch repair genes or MSI-high tumors without germline alteration who underwent NU achieved &lt;ypT2pN0 and remain free of disease. Clinical trial information: NCT03520491 .

Application of the single-port robotic platform during radical nephroureterectomy for upper tract urothelial carcinoma: feasibility of the single-port robot in the multi-quadrant setting.

Urothelial carcinoma of the upper tract (UTUC) is a malignancy that accounts for 5-10% of all urothelial carcinomas. Radical surgery is the primary treatment option due to the high rate of invasive stages at the time of diagnosis. Nephroureterectomy (NU) with bladder cuff excision is the current standard of care. While laparoscopic NU has been established since 1991, many centres still perform open surgery due to the complexity of laparoscopic instrumentation and the steep learning curve for excising the bladder cuff. With the increasing adoption of the multi-port (MP) robotic surgery, NU has increasingly been performed using this platform. The use of MP robotic systems for NU has been challenged by the need for patient repositioning and/or redocking of the robot, which can consume valuable operative time. The transition from the daVinci Si to the daVinci Xi system has seen a noticeable reduction in redocking and patient repositioning. However, owing to the multi-quadrant nature of the surgery in question, the use of multiple ports and external instrument clashing are still persistent problems. Moreover, there is a growing interest in utilizing a retroperitoneal approach for robot-assisted NU due to its potential benefits such as improved control of hilar structures, reduction of blood loss, shorter operative time and hospital stay, reduced complications and decreased postoperative discomfort. The application of the daVinci single-port (SP) robotic platform during radical NU for UTUC is feasible and has the potential to improve the current surgical approach. Indeed, the use of a SP platform may solve the problem of patient repositioning and redocking of the robot, improve superficial aesthetic outcome and minimize external instrument clashing. While maintaining an optimal oncological control, the retroperitoneal approach, which has been difficult to replicate and adopt using the MP approach, may become standard practice. However, more studies are needed to confirm the benefit of this approach and ultimately determine the impact of the daVinci SP on the management of UTUC.

Preoperative chemotherapy for patients with upper tract urothelial carcinoma: Impact on renal function

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. A single center retrospective study was performed on patients with UTUC who received POC. 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%. 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 impact of routine frozen section analysis during nephroureterectomy or segmental ureterectomy for urothelial carcinoma on final surgical margin status and long-term oncologic outcome.

The utility of intraoperative frozen section analysis (FSA) at the surgical margins (SMs) in patients with upper urinary tract cancer has not been established. We herein assessed the clinical significance of routine FSA of ureteral SMs during nephroureterectomy (NU) or segmental ureterectomy (SU). A retrospective review of our Surgical Pathology database identified consecutive patients undergoing NU (n=246) or SU (n=42) for urothelial carcinoma from 2004 to 2018. FSA (n=54) was correlated with the diagnosis of frozen section controls, the status of final SMs, and the prognosis of patients. During NU, FSA was performed in 19 (7.7%) patients and was significantly more often requested in cases with ureteral tumor (13.1%) than in those with renal pelvis/calyx tumor (3.5%). Final SMs at the distal ureter/bladder cuff were positive only in non-FSA cases in the entire NU cohort (8.4%; P=0.375) or those with tumor at the lower ureter (57.6%; P=0.046), but not in any of FSA patients (0%). During SU, FSA was performed in 35 (83.3%) cases, including 19 at either proximal or distal SM and 16 at both SMs (SU-FSA2). Final positive SMs were significantly more often detected in non-FSA patients (42.9%) than in all FSA (8.6%; P=0.048) or SU-FSA2 (0%; P=0.020) patients. Overall, FSAs were reported as positive or high-grade carcinoma (n=7), atypical or dysplasia (n=13), and negative (n=34), and all these diagnoses were confirmed accurate on the frozen section controls, except one with a revision from atypical to carcinoma in situ. Meanwhile, 16 (80.0%) of 20 cases with initial positive/atypical FSA achieved negative conversion by excision of additional tissue. Kaplan-Meier analysis revealed that SU-FSA did not significantly reduce the risk of tumor recurrence in the bladder, disease progression, or cancer-specific mortality. Nonetheless, NU-FSA was strongly associated with reduced progression-free (P=0.023) and cancer-specific (P=0.007) survival rates, compared with non-FSA, which may imply a selection bias (e.g., FSA for clinically more aggressive tumors). Performing FSA during NU for lower ureteral tumor, as well as during SU, significantly reduced the risk of positive SMs. However, routine FSA for upper urinary tract cancer failed to considerably improve long-term oncologic outcome.

Comparison of reduced lead sets in detection of common ECG abnormalities

The utility of intraoperative frozen section analysis (FSA) at the surgical margins (SMs) in patients with upper urinary tract cancer has not been established. We herein assessed the clinical significance of routine FSA of ureteral SMs during nephroureterectomy (NU) or segmental ureterectomy (SU).A retrospective review of our Surgical Pathology database identified consecutive patients undergoing NU (n=246) or SU (n=42) for urothelial carcinoma from 2004 to 2018. FSA (n=54) was correlated with the diagnosis of frozen section controls, the status of final SMs, and the prognosis of patients.During NU, FSA was performed in 19 (7.7%) patients and was significantly more often requested in cases with ureteral tumor (13.1%) than in those with renal pelvis/calyx tumor (3.5%). Final SMs at the distal ureter/bladder cuff were positive only in non-FSA cases in the entire NU cohort (8.4%; P=0.375) or those with tumor at the lower ureter (57.6%; P=0.046), but not in any of FSA patients (0%). During SU, FSA was performed in 35 (83.3%) cases, including 19 at either proximal or distal SM and 16 at both SMs (SU-FSA2). Final positive SMs were significantly more often detected in non-FSA patients (42.9%) than in all FSA (8.6%; P=0.048) or SU-FSA2 (0%; P=0.020) patients. Overall, FSAs were reported as positive or high-grade carcinoma (n=7), atypical or dysplasia (n=13), and negative (n=34), and all these diagnoses were confirmed accurate on the frozen section controls, except one with a revision from atypical to carcinoma in situ. Meanwhile, 16 (80.0%) of 20 cases with initial positive/atypical FSA achieved negative conversion by excision of additional tissue. Kaplan-Meier analysis revealed that SU-FSA did not significantly reduce the risk of tumor recurrence in the bladder, disease progression, or cancer-specific mortality. Nonetheless, NU-FSA was strongly associated with reduced progression-free (P=0.023) and cancer-specific (P=0.007) survival rates, compared with non-FSA, which may imply a selection bias (e.g., FSA for clinically more aggressive tumors).Performing FSA during NU for lower ureteral tumor, as well as during SU, significantly reduced the risk of positive SMs. However, routine FSA for upper urinary tract cancer failed to considerably improve long-term oncologic outcome.

Abstract 3349: Discovery and validation of methylated DNA markers of upper tract urothelial tract cancers

Abstract Objective: Upper tract urothelial cancers (UTUC) can be difficult to characterize, and non-invasive surveillance tools are lacking. UTUC are often treated with nephroureterectomy (NU). To address these gaps, we sought to discover and validate methylated DNA markers (MDMs) for detection of UTUC. Methods: Archival formalin fixed paraffin embedded (FFPE) tissue samples from NU were pathologically reviewed and punched prior to DNA extraction. Reduced representation bisulfite sequencing (RRBS) was used to identify candidate MDMs that discriminated between UTUC and age-balanced control urothelial tissues (uninvolved ureter/renal pelvic of renal cell carcinoma at radical nephrectomy). Highest ranked (fold-change and p-value) candidate MDMs were biologically validated by quantitative methylation specific PCR in a 2nd independent set of UTUC and age-balanced controls. DNA from healthy donor urine and buffy coat samples was used to assess MDM background signal. Discrimination between UTUC and controls was assessed as the area under the receiver operator characteristic curve (AUC) with corresponding 95% confidence intervals. Results: RRBS assessed 33 UTUC and 26 ureter/renal pelvis controls. 3.01 x 106 CpGs mapped to the reference genome with at least 10X read depth. From 358 candidates, 20 MDMs were selected for biological validation in independent patient samples which included 20 renal pelvis &amp; 16 ureter UTUC and 17 renal pelvis &amp; 15 ureter control specimens. Of UTUC and control patients, 36% and 65% of were men, respectively. Median AUC for comparison of UTUC vs control tissue was 0.87 (IQR 0.81-0.88); AUCs with corresponding 95% CIs are shown for the 10 most accurate MDMs (Table) across all control types. Conclusion: We report discovery and validation of highly sensitive and specific MDMs with potential for accurate non-invasive screening supported by low background in urine and blood. AUCs (95% CI) for selected methylated DNA markers for UTUC vs control tissue, urine, and blood UTUC vs Marker Control Tissue Control Urine Control Buffy C2orf55 0.92 (0.84-1) 0.93 (0.87-1) 0.96 (0.91-1) ANKRD35 0.91 (0.84-0.99) 0.93 (0.86-1) 0.98 (0.94-1) DLX6 0.91 (0.84-0.98) 0.78 (0.66-0.9) 0.97 (0.93-1) Chr8.9998 0.90 (0.82-0.97) 0.91 (0.84-0.97) 0.98 (0.96-1) SP9 0.88 (0.8-0.97) 0.95 (0.9-1) 0.99 (0.98-1) Chr13.1127 0.88 (0.8-0.97) 0.94 (0.89-1) 0.92 (0.85-1) Septin9.r2 0.88 (0.79-0.97) 0.95 (0.88-1) 0.98 (0.94-1) LBX2 0.88 (0.79-0.97) 0.94 (0.88-1) 0.96 (0.91-1) SIM2.r1 0.88 (0.79-0.97) 0.91 (0.82-1) 0.94 (0.86-1) Chr14.1037 0.88 (0.78-0.97) 0.93 (0.85-1) 0.96 (0.9-1) Citation Format: Ojas Bhagra, William R. Taylor, Benjamin R. Gochanour, Patrick H. Foote, Calise K. Berger, Xiaoming Cao, Douglas W. Mahoney, Sara S. Then, Anna M. Gonser, Karen A. Doering, Kelli N. Burger, John C. Cheville, Matthew T. Gettman, John B. Kisiel. Discovery and validation of methylated DNA markers of upper tract urothelial tract cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3349.

MP69-16 INPATIENT OUTCOMES OF RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CANCER, WITH TRENDS IN UTILIZATION AND IMPACT OF ROBOTIC SURGERY: A NATIONAL INPATIENT SAMPLE ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP69-16 INPATIENT OUTCOMES OF RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CANCER, WITH TRENDS IN UTILIZATION AND IMPACT OF ROBOTIC SURGERY: A NATIONAL INPATIENT SAMPLE ANALYSIS Sohrab Arora, Samantha Wilder, Matthew Davis, Nicholas Corsi, Ivan Rakic, Chase Morrison, Rafe Affas, Akshay Sood, Riccardo Autorino, Craig Rogers, and Firas Abdollah Sohrab AroraSohrab Arora More articles by this author , Samantha WilderSamantha Wilder More articles by this author , Matthew DavisMatthew Davis More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Ivan RakicIvan Rakic More articles by this author , Chase MorrisonChase Morrison More articles by this author , Rafe AffasRafe Affas More articles by this author , Akshay SoodAkshay Sood More articles by this author , Riccardo AutorinoRiccardo Autorino More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Our primary aim was to evaluate the inpatient morbidity, mortality, and cost of radical nephroureterectomy (NU) for upper tract urothelial cancer (UTUC). We also aimed to evaluate the trends in utilization of robotic surgery for this procedure, and to assess the difference between robotic NU and open NU in terms of the above outcomes from within the National Inpatient Sample (NIS). METHODS: We focused on 9581 records of adult patients with nonmetastatic UTUC undergoing radical NU from 2003-14, representing an estimated 47204 NUs performed in the US during this period. Data after 2014 was excluded due to International Classification of Diseases (ICD) coding change in 2015. ICD-9 code for robotics was introduced in 2008, so data before 2008 was not used when comparing surgical approaches. ICD-9 codes were used to define complications. Complex-survey procedures were used to study descriptive characteristics, and outcomes of patients undergoing NU. Cost of admission was inflation-adjusted to 2014 US dollars. Table: Descriptive statistics and outcomes of radical NU for upper tract urothelial carcinoma in 47204 records from the NIS from 2008-2014, stratified by surgical approach. RESULTS: Overall, the median age of the patients was 72 (IQR 63-79) years. 22974 (49%) patients had a Charlson comorbidity index of 3 or more. 33693 (71%) patients had Medicare/Medicaid insurance. 14692 (31%) patients had complications, with 6814 (14%) having major complications. Significant trend towards use of robotic approach was seen during the study period. Overall, 4635 NUs were performed robotically: accounting for 33% of NUs in 2014. Table 1 shows the outcomes after stratification by approach. Robotic surgery was associated with significantly lower rate of any complications 962 (21%) vs 7675 (33%) for open; p<0.001. This was also true for in hospital mortality (0.3% vs 1.2%; p 0.02), and major complications (10% vs 19%; p<0.001). CONCLUSIONS: Nephroureterectomy is associated with a high inpatient morbidity and mortality. There is increasing utilization of robotic approach in the US. Robotic surgery is associated with lower morbidity and in hospital mortality in these patients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e970 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sohrab Arora More articles by this author Samantha Wilder More articles by this author Matthew Davis More articles by this author Nicholas Corsi More articles by this author Ivan Rakic More articles by this author Chase Morrison More articles by this author Rafe Affas More articles by this author Akshay Sood More articles by this author Riccardo Autorino More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

MP69-15 RESPONSE TO CHECKPOINT BLOCKADE IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA AND LYNCH SYNDROME

You have accessJournal of UrologyCME1 Apr 2023MP69-15 RESPONSE TO CHECKPOINT BLOCKADE IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA AND LYNCH SYNDROME Alexander Doudt, Wesley Yip, Daniel Sjoberg, Gopa Iyer, Min Teo, and Jonathan Coleman Alexander DoudtAlexander Doudt More articles by this author , Wesley YipWesley Yip More articles by this author , Daniel SjobergDaniel Sjoberg More articles by this author , Gopa IyerGopa Iyer More articles by this author , Min TeoMin Teo More articles by this author , and Jonathan ColemanJonathan Coleman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immune checkpoint inhibition (ICI) has shown effective results in treating Lynch Syndrome (LS)-associated and microsatellite instability-high (MSI-H) malignancies. However, there is a paucity of information evaluating its use in patients with LS-associated upper tract urothelial carcinoma (UTUC). Our objective was to describe our clinical experience in treating LS-associated UTUC with checkpoint blockade. METHODS: All patients with LS-associated or MSI-H UTUC who received treatment with ICI at Memorial Sloan Kettering were retrospectively identified. Demographic and clinicopathological characteristics were collected. Patient outcomes were illustrated using a swimmer’s plot beginning at the initiation of ICI. For patients with metastatic disease, response to therapy was assessed by radiographic progression. For localized disease, pathologic response and time to urothelial recurrence were summarized. RESULTS: We identified 10 patients with LS-associated UTUC, 6 with metastatic and 4 with localized disease, who were treated with ICI (2015 to present). Seven patients had solitary kidneys [prior nephroureterectomy (NU)]. Two patients received ICI as neoadjuvant treatment prior to NU. Of the 4 patients with localized disease, 75% (3/4) had a complete response, including ypT0 after NU (2) and clinically pT0 based on endoscopic, cytologic, and radiographic findings. Median follow-up of the localized cohort was 5.6 months. One patient had urothelial recurrence at 6 months that was successfully treated with endoscopic ablation. Of the 6 patients with metastatic disease, 67% (4/6) were progression-free at 24-months. CONCLUSIONS: These preliminary findings provide supporting evidence for prospective studies to further assess the safety and efficacy of ICI for LS-associated UTUC in settings such as neoadjuvant therapy and as an organ-sparing option for patients with a solitary kidney. Source of Funding: MSKCC Sidney Kimmel Center for Prostate and Urologic Cancers © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e970 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Doudt More articles by this author Wesley Yip More articles by this author Daniel Sjoberg More articles by this author Gopa Iyer More articles by this author Min Teo More articles by this author Jonathan Coleman More articles by this author Expand All Advertisement PDF downloadLoading ...

PD46-05 GENETIC ABERRATIONS IDENTIFIED IN FOCAL BARBOTAGES– a COMPLEMENTARY DIAGNOSTIC TOOL IN UPPER TRACT UROTHELIAL CARCINOMA (UTUC)

You have accessJournal of UrologyCME1 Apr 2023PD46-05 GENETIC ABERRATIONS IDENTIFIED IN FOCAL BARBOTAGES– a COMPLEMENTARY DIAGNOSTIC TOOL IN UPPER TRACT UROTHELIAL CARCINOMA (UTUC) Tomas Axelsson, Filip Sydén, Jesper Eisfeldt, Ylva Eriksson, Gustav Göthner Lundberg, Alexandra Grahn, Emma Tham, and Marianne Brehmer Tomas AxelssonTomas Axelsson More articles by this author , Filip SydénFilip Sydén More articles by this author , Jesper EisfeldtJesper Eisfeldt More articles by this author , Ylva ErikssonYlva Eriksson More articles by this author , Gustav Göthner LundbergGustav Göthner Lundberg More articles by this author , Alexandra GrahnAlexandra Grahn More articles by this author , Emma ThamEmma Tham More articles by this author , and Marianne BrehmerMarianne Brehmer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: UTUC is divided into low- and high risk UTUC. Despite radical surgery, 10-20% in the low-risk and 50% of the patients in the high-risk group respectively, recur and die from UTUC. Although tumour stage and grade are known prognostic factors, the mechanisms of recurrence in each risk group respectively are not entirely known. In a previous study of genetic analysis of tumour tissue from nephroureterectomy (NU) we showed that gene mutations in some cases had a stronger prognostic value than histopathology. We have also previously shown that cytology taken as focal barbotage, at ureterorenoscopy (URS), renders good diagnostic material. The aim of this study was to investigate if gene analysis of focal barbotages obtained at URS is possible. In addition, we tried to identify gene mutations and copy number variations (CNV) that might signify a more aggressive tumour. METHODS: This prospective study included 41 patients with UTUC confirmed at URS from 2018 to 2021. Patients were followed until October 2022. At URS, barbotage specimens from the ureter and renal pelvis were collected and sent for cytology analysis and for gene sequencing. When possible, tumour biopsies were taken. Final tumour grades (WHO-classifications 1999 and 2004) were determined from cytology and/or biopsy, or from radical NU samples when available. A total of 41 barbotage samples were sent for genetic analysis. Next generation sequencing using a 388-gene panel was performed. Manual filtering of the sequencing data from each sample was performed to identify possible pathogenic mutations. CNV was analysed using WisecondorX. RESULTS: 41 patients, 26 men and 15 women were included. Mean age at inclusion was 75 years. In 14 patients the tumour was low grade (8 G1, 5 G2 and one unclear) and in 27 patients the tumour was high grade (14 G2 and 13 G3). During the follow-up period, 5 patients died from UTUC and 7 patients had tumour progression. Out of 41 focal barbotages analysed we identified known and suspected pathogenic mutations in 39 and CNVs in 32. Known pathogenic mutations in the fibroblast growth receptor 3 (FGFR3) gene were common in grade 1 and 2 tumours but not present in any G3 tumour. No patients with a FGFR3 mutation died during follow-up. Seven patients had a pathogenic mutation in tumour protein 53 (TP53), 6 of these had high grade tumours, 2 of whom died from UTUC during follow-up. One patient with a TP53 mutation had a low grade, G1-tumor, that progressed with metastasis during follow up. CONCLUSIONS: Gene mutations and CNVs can be identified in focal barbotage samples obtained at URS and may be complementary to cytologic analysis. The technique may be helpful in identifying low risk tumours that might be more at risk for disease progression or death than previously thought. Source of Funding: Nothing to declare © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1171 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomas Axelsson More articles by this author Filip Sydén More articles by this author Jesper Eisfeldt More articles by this author Ylva Eriksson More articles by this author Gustav Göthner Lundberg More articles by this author Alexandra Grahn More articles by this author Emma Tham More articles by this author Marianne Brehmer More articles by this author Expand All Advertisement PDF downloadLoading ...

Neoadjuvant nivolumab (N) + ipilimumab (I) in cisplatin-ineligible patients with upper tract urothelial cancer (UTUC).

511 Background: Perioperative platinum-based chemo for UTUC improves pathologic responses and disease-free survival (DFS) while anti-PD1 monotherapy has limited activity to date (PURE-02). Here, we report the results from stage 1 of a phase II neoadjuvant trial of N+I for cisplatin-ineligible patients (pts) with UTUC. Methods: Cisplatin-ineligible pts with histologically confirmed high-grade UTUC and/or radiographically invasive UTUC with positive selective urine cytology were eligible. Pts were treated with I 3mg/kg + N 1mg/kg (weeks [wk] 0, 6), and N 3mg/kg (wk 3) prior to radical nephroureterectomy (NU). The primary endpoint (EP) was pathologic complete response (pCR, ypT0pN0) and secondary EPs included &lt;ypT2pN0 rate, DFS, and toxicity. The study has a Simon optimal two-stage design: if ≥1/9 pts achieved pCR in stage 1, the trial would proceed to accrue 24 total pts. Next generation sequencing of pre-treatment tumors was correlated with pathologic response. Results: Nine pts were enrolled between 2/2021-7/2022 with median age 71 (range 62-86), 89% male. Primary sites included ureter, n=6; renal pelvis, n=2; and both, n=1. Four pts (44%) had hydronephrosis. Median tumor diameter was 3.0 cm, (range: not measurable to 4.2 cm). Six pts (67%) received all planned treatment; N+/-I was stopped early for CTCAE grade 2 hyperthryoidism, n = 1; grade 2 diarrhea, n = 1; and grade 3 pneumonitis, n = 1. Median time from last treatment to NU was 1.7 months (range 0.6-3.7). No progression was noted on systemic therapy and all pts underwent NU, with pCR in 3/9 pts (33%) and &lt;ypT2pN0 in 6/9 (67%). Two pts had metastatic recurrence at 10.3 and 15.6 months after treatment initiation, while 1 pt died of post-op complications related to bowel leak 7.2 months after N+I initiation (4.7 months after NU) and 1 died 9.2 months after N+I initiation (4.7 months after NU) from complications of a fall unrelated to disease, surgery or N+I. Median tumor mutational burden (TMB) in 7 pts with pre-treatment sequencing was 13.2 mutations/megabase (range 6.6-106.3); all 3 pts with TMB&lt;10 were &gt;ypT1 or node positive at NU and all 4 pts with TMB&gt;10 were &lt;ypT1pN0. Three pts (43%) had FGFR3 driver mutations. Three pts had confirmed pathogenic germline variants in mismatch repair genes (MSH2, n=2; MLH1, n=1), all of which achieved pCR (n=1) or ypTaN0 (n=2) and remained alive and disease-free at last follow-up. CTCAE grade ≥3 treatment-related adverse events occurred in 4 pts (1 myasthenia, 1 maculopapular rash, 1 pneumonitis, 1 hepatitis plus elevated lipase). Conclusions: In this cohort of cisplatin-ineligible pts with UTUC, neoadjuvant N+I showed clinical activity meeting the trial’s Simon optimal two-stage design’s criteria to proceed to the second stage. All pts with pathogenic germline variants in mismatch repair genes achieved &lt;ypT1pN0 and remain free of disease. Clinical trial information: NCT03520491 Clinical trial information: NCT03520491 .

Inpatient outcomes of radical Nephroureterectomy (NU) for Upper Tract Urothelial Cancer (UTUC), with trends in utilization and impact of robotic surgery – National Inpatient Sample (NIS) analysis

Inpatient outcomes of radical Nephroureterectomy (NU) for Upper Tract Urothelial Cancer (UTUC), with trends in utilization and impact of robotic surgery – National Inpatient Sample (NIS) analysis

Body Composition as a Comorbidity-Independent Predictor of Survival following Nephroureterectomy for Urothelial Cancer of the Upper Urinary Tract.

Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02-3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18-3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification.

Biopsy with Ureterorenoscopy Before Radical Nephroureterectomy is Associated with Increased Intravesical Recurrence in Urothelial Cancer Located in the Kidney.

Diagnostic ureterorenoscopy is used to identify upper tract urothelial cancer before radical nephro ureterectomy, especially for uncertain lesions in imaging modalities or urine cytology. However, diagnostic ureterorenoscopy can potentially cause intravesical tumor spillage and can increase intravesical recurrence rates. We aimed to investigate the impact of diagnostic ureterorenoscopy before radical nephroureterectomy, with and without biopsy, on intravesical recurrence rates of patients with upper tract urothelial cancer. Patients with localized upper tract urothelial cancer from 8 different tertiary referral centers, who underwent radical nephroureterectomy between 2001 and 2020, were included. Three groups were made: no URS (group 1); diagnostic ureterorenoscopy without biopsy (group 2); and diagnostic ure terorenoscopy with biopsy (group 3). Intravesical recurrence rates and survival outcomes were compared. Univariate and multivariate Cox regression analyses were performed to determine the factors that were asso ciated with intravesical recurrence-free survival. Twenty-two (20.8%), 10 (24.4%), and 23 (39%) patients experienced intravesical recurrence in groups 1, 2, and 3, respectively (P=.037) among 206 patients. The 2-year intravesical recurrence-free sur vival rate was 83.1%, 82.4%, and 69.2%, for groups 1, 2, and 3, respectively (P=.004). Cancer-specific survival and overall survival were comparable (P=.560 and P=.803, respectively). Diagnostic ureterore noscopy+biopsy (hazard ratio: 6.88, 95% CI: 2.41-19.65, P < .001) was the only independent predictor of intravesical recurrence in patients with upper tract urothelial cancer located in the kidney, according to tumor location. Diagnostic ureterorenoscopy+biopsy before radical nephroureterectomy significantly increased the rates of intravesical recurrence in tumors located in kidney. This result suggests tumor spillage with this type of biopsy, so further studies with different biopsy options or without biopsy can be designed.

Diode Laser for the Management of Upper Tract Urothelial Cancer (UTUC) – Case Series.

Background and Objective: Upper tract urothelial carcinoma (UTUC) is uncommon; however, at the time of diagnosis, they are usually more invasive than bladder urothelial carcinomas. Although nephroureterectomy (NU) has been the gold-standard treatment, guidelines have been set for kidney-sparing treatment in selected groups of patients. While these guidelines are aimed towards patients fit for salvage radical treatment, little has been published on managing the symptomatic patient not fit for NU. Various modalities of endoscopic ablation in managing UTUC have been described in the literature, but there is currently no reported use of the diode laser. Therefore, we aim to assess its efficacy and safety profile in the ablation of UTUC in patients unfit for major abdominal surgery in radical nephroureterectomy regardless of the tumour grade and size. Patients and method A single centre retrospective review of patients who underwent Diode Laser treatment for UTUC over 4 years was done. Follow up through 6 monthly ureteroscopy alternating with computed tomography (CT) urogram was done to assess the need for further treatment. Results: 30 patients were identified, with mean age 76 years (64-88) and variable tumour locations, including lower and mid ureter and renal pelvis, upper and lower calyces. 76.7% were ASA 3 and 20% ASA 4. The mean tumour size was 3.8 cm (2-7 cm). The mean number of sessions was 2.1 (1-6). 63.3% of the tumours were grade 2, while 30% were grade 3. A case of metastatic renal-cell carcinoma was diagnosed as a 4 cm filling defect in the kidney where the diode laser was used for resection biopsy and ablation. 16.7% experienced Clavien-Dindo grades 1-2 complications. A total of 6.7% of patients were converted to an inpatient stay. None of the patients needed blood transfusion nor did any develop a ureteric stricture on subsequent ureteroscopies. 48.3% of patients experienced clinical recurrences of which 57.1% were at a different site. Two of the patients developed metastatic disease. One patient died 3 years after initial treatment with disease progression. Conclusion: The management of UTUC with diode laser is a safe and efficacious conservative treatment for disease and symptom control in patients unfit for radical treatment.

Inadvertent radical nephrectomy leads to worse prognosis in renal pelvic urothelial carcinoma patients: A propensity score-matched study.

ObjectiveTo compare overall survival (OS) and cancer-specific survival (CSS) in renal pelvic urothelial carcinoma (RPUC) patients treated with radical nephroureterectomy (NU) and inadvertent radical nephrectomy (RN).Patients and methodsIn this retrospective study, patients with RPUC who underwent NU or RN diagnosed between 2004 and 2017 were identified from the Surveillance, Epidemiology, and End Results database. To adjust the confounders, the propensity score-matched analysis was conducted. The Kaplan–Meier method and log-rank test were performed to explore the effect of different surgical methods on OS and CSS.ResultsA total of 2197 cases were finally included in this analysis, among which, 187 (8.5%) patients were treated with RN and 2010 (91.5%) patients were treated with NU. Before matching, the survival analysis revealed that the OS (HR: 1.444, 95%CI: 1.197, 1.741) and CSS (HR: 1.522, 95%CI: 1.211, 1.914) of patients who received RN were worse than that of patients who received NU (p = 0.0001 and p = 0.0003, respectively). After matching, the RN group had a worse OS (HR: 1.298, 95%CI: 1.002, 1.682) than the NU group (p = 0.048). No significant difference was observed in CSS between the RN and NU groups (p = 0.282). The hierarchical analysis showed that there was no significant difference observed in OS and CSS in patients with tumor size ≤4.2 cm (p = 0.884 and p = 0.496, respectively). In tumor size >4.2 cm, both OS (HR: 1.545, 95%CI: 1.225, 1.948) and CSS (HR: 1.607, 95%CI: 1.233, 2.095) of patients who received RN were worse than those of patients who received NU (p = 0.0002 and p = 0.0005).ConclusionRN could lead to worse oncological outcomes than NU in patients with renal pelvis urothelial carcinoma. Accurate diagnosis of renal pelvis urothelial carcinoma is extremely important.