Carcinoma Of Upper Urinary Tract Research Articles

WUTSUP-02-II-Neo-Dis-Tis: Investigating the efficacy and safety of neoadjuvant tislelizumab plus disitamab vedotin with adjuvant tislelizumab in upper urinary tract carcinoma—A phase II multi-center study.

TPS718 Background: Upper tract urothelial carcinoma (UTUC) and urothelial bladder cancer (UBC) are frequently referred to as “disparate twins” despite their common tissue origin. They exhibit varying biological behaviors, prognostic outcomes, and responses to treatment. It is crucial to conduct dedicated clinical trials for UTUC as a separate entity rather than relying solely on UBC study results, giving that UTUC lags in evidence quantity and quality compared to UBC. Despite the superior outcomes of neoadjuvant treatment over adjuvant treatment in UBC trials, the currently available evidence for neoadjuvant therapy of UTUC remains limited in quantity and diversity, as the largest trial, POUT, is focused on adjuvant therapy. Additionally, the limited number of neoadjuvant trials for UTUC primarily utilize chemotherapy-based regimens, with little investigation into combination therapies. Of note, UTUC patients frequently have impaired renal functions, making a chemotherapy-independent approach a desirable alternative. On the other hand, given the short duration of neoadjuvant therapy, a combination therapy strategy appears to be necessary, especially with the increasing interest in immune therapy maintenance after surgery. Tislelizumab has demonstrated efficacy in patients with advanced or metastatic urothelial carcinoma. Disitamab Vedotin, a HER2-targeting antibody-drug conjugate (ADC), has demonstrated robust clinical efficacy in metastatic urothelial carcinoma patients with HER2 2+ or 3+ expression. Disitamab Vedotin in combination with PD-1 immunotherapy has shown remarkable results in locally advanced or metastatic urothelial carcinoma, regardless of HER2 expression, indicative of a synergistic effect between ADC and PD-1 immunotherapy. In this study, we aim to conduct a prospective phase II trial to investigate the efficacy and safety of neoadjuvant tislelizumab plus Disitamab Vedotin followed by adjuvant tislelizumab in patients with high-risk UTUC. Methods: This multi-center phase II trial aims to enroll 45 patients with histologically confirmed UTUC at clinical stage cT2-4N0M0 or cT1-4N1-2M0. Neoadjuvant therapy includes 4 cycles of Tislelizumab (200mg for each 3-week cycle) in combination with Disitamab Vedotin (2.0mg/kg for each 3-week cycle). Radical nephroureterectomy (including bladder cuff resection and regional lymph node dissection if indicated) will be performed if there is no obvious contraindication within 3-6 weeks after the final neoadjuvant therapy administration. Postoperative adjuvant treatment with 8 cycles of tislelizumab will be provided. The primary endpoint is pathological complete response rate. Secondary endpoints include overall survival, local recurrence free survival, distant metastasis free survival, FACT–G. Clinical trial information: ChiCTR2300067836 .

Contemporary Issues in Urothelial Carcinoma of Upper Urinary Tract.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon malignancy involving the renal pelvis and ureter. Careful pathologic analysis plays a critical role in the diagnosis and clinical management of UTUC. In combination with clinical and radiologic evaluation, pathologic features can be used to stratify patients into low-risk and high-risk groups. This risk stratification can help clinicians select the optimal treatment for patients with UTUC, such as kidney-sparing (conservative) treatment, radical nephroureterectomy or ureterectomy, and perioperative systemic therapy. However, due to the technical difficulty of obtaining sufficient tissue from the upper urinary tract, it is often challenging for pathologists to accurately grade the tumor and assess tumor invasion in small biopsy specimens. Although the majority of UTUCs are pure urothelial carcinoma, a considerable subset of UTUCs show histologic subtypes or divergent differentiation. Recent studies have identified genetically distinct molecular subtypes of UTUC by examining DNA, RNA, and protein expression profiles. The prognosis of pT3 UTUC, particularly renal pelvic UC, remains controversial, and several studies have proposed subclassification of pT3 UTUC. Lynch syndrome is a significant risk factor for UTUC, and screening tests may be considered in young patients and those with familial histories of the disease. Despite significant progress in recent years, several issues remain to be addressed in the pathologic diagnosis, molecular classification, and treatment of UTUC.

253TiP WUTSUP-02-II-Neo-Dis-Tis: Investigating the efficacy and safety of neoadjuvant tislelizumab plus disitamab vedotin with adjuvant tislelizumab in upper urinary tract carcinoma: A phase II multi-center study

253TiP WUTSUP-02-II-Neo-Dis-Tis: Investigating the efficacy and safety of neoadjuvant tislelizumab plus disitamab vedotin with adjuvant tislelizumab in upper urinary tract carcinoma: A phase II multi-center study

A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients

BackgroundCurrently, the clinical strategy for diagnosis of non-muscle invasive bladder cancer (NMIBC) such as cystoscopy and cytology are invasive and/or with limited accuracy. OncoUrine, a urinary assay for mutation and methylation biomarkers, have showed a high accuracy in the detection of upper tract urinary carcinoma (UTUC) patients with hematuria. The aim of this study is to evaluate the performance of OncoUrine in diagnosis of NMIBC patients.MethodsIn this multicenter prospective study, a total of 203 patients were enrolled, including 60 patients present with hematuria and 143 NMIBC patients under recurrence surveillance. Urine samples were collected before cystoscopy to undergo OncoUrine test. OncoUrine performance was calculated compared to clinical standard methods in hematuria cohort and recurrence surveillance cohort, respectively. Furthermore, NMIBC patients were followed up with a median time of 20.5 months (range 0.03 to 24.03 months) to assess the predictive value of OncoUrine during recurrence monitoring.ResultsFor bladder cancer diagnosis, OncoUrine tested 47 samples and achieved a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 80% (95% CI 44.2–96.5)/91.9% (95% CI 77.0–97.9)/72.7% (95% CI 39.3–92.7)/94.4% (95% CI 80.0–99.0) (kappa value 69.4%, 95% CI 44.4–94.3), indicating 72.3% of unnecessary cystoscopy. For recurrence diagnosis, OncoUrine tested 93 samples, and the sensitivity/specificity/PPV/NPV was 100% (95% CI 59.8–100.0)/68.2% (95% CI 57.1–77.7)/22.9% (95% CI 11.0–40.6)/100% (95% CI 92.3–100.0) (kappa value 27.0%, 95% CI 11.1–42.8), indicating 62.4% of spared cystoscopy. What is more, OncoUrine correctly predicted 80% (20/25) of final recurrence with 12/25 (48%) patients who were OncoUrine positive, but cystoscopy negative was followed with recurrence during follow-up. The test result of OncoUrine was also found significantly correlated with recurrence free survival (RFS) of NMIBC patients (median 34.4-month vs unreached; HR 6.0, 95% CI 2.7–13.5, P < 0.0001).ConclusionsOncoUrine showed potential value to reduce the frequency of unnecessary cystoscopy and the healthcare cost of bladder cancer patients. Patients with positive test results represented a population who were at high risk of recurrence and thus should be subject to frequent surveillance to ensure timely detection of any potential recurrence. This study has been registered in ClinicalTrials.gov with the number NCT04994197 posted on August 2021.

Clinical characteristics and treatment outcomes of kidney transplant recipients with de novo urothelial carcinoma: thirty years of experience from a single center

BackgroundDe novo urothelial carcinoma (UC) is a leading cause of death after kidney transplant (KT). The efficacy of various treatments, apart from surgery, and the prognosis for patients with urothelial carcinoma after kidney transplantation remain unclear.MethodsWe retrospectively reviewed the efficacy of chemotherapy with gemcitabine + cisplatin (GC) or gemcitabine + carboplatin (GCa), bladder infusion chemotherapy, and immunosuppression therapy for de novo UC in kidney transplantation recipients at different sites and T stages. We evaluated the prognosis and compared the difference using Kaplan-Meier analysis and the log-rank test.ResultsOf the 97 kidney transplantation recipients with de novo UC, 51 (52.6%) were diagnosed with upper urinary tract carcinoma (UTUC), 17 (17.5%) with bladder carcinoma (BC), and 29 (29.9%) with both UTUC and BC. The five-year survival rates for BC, UTUC, and BC + UTUC with ≤ T1 stage were 100%, 88.2%, and 57.7%, respectively, while the survival rates for UTUC, BC + UTUC with ≥ T2 stage were 90.2% and 48.2%. Cyclosporine A significantly improved progression-free survival (PFS) in UTUC with ≤ T1 stage (p = 0.017). Rapamycin significantly improved PFS in UTUC with ≥ T2 stage (p = 0.026). Bladder infusion chemotherapy and GC/GCa chemotherapy had no significant effect on each T stage and site. Patients with UTUC + BC had the poorest overall survival (OS) compared with those with BC and UTUC.ConclusionThe prognosis of UC in different sites varies. GC/GCa chemotherapy and bladder infusion chemotherapy appear to have no effect on prognosis. Rapamycin can delay the progression of advanced UTUC.

Diagnostic Imaging in the Evaluation of Asymptomatic Microhematuria: Systematic Review and Meta-analysis.

Microhematuria is a highly prevalent condition with a low associated risk of urothelial and upper tract malignancy. The AUA Guidelines recently changed recommendations for imaging favoring renal ultrasound for low and intermediate risk patients with microhematuria. We summarize the diagnostic test characteristics of computed tomography urography, renal ultrasound, and magnetic resonance urography in comparison with surgical pathology for the diagnosis of upper urinary tract cancer in microhematuria and gross hematuria patients. This study is a systematic review and meta-analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from evidence collected for the 2020 AUA Microhematuria Guidelines report, including studies assessing imaging following diagnosis of hematuria published from January 2010 through December 2019. The search identified 20 studies which reported the prevalence of malignant and benign diagnoses in relation to imaging modality, of which 6 were included in the quantitative analysis. For the detection of renal cell carcinoma and upper urinary tract carcinoma in patients with microhematuria and gross hematuria, computed tomography urography had a sensitivity of 94% (95% CI, 84%-98%) and a specificity of 99% (95%CI, 97%-100%) with a certainty of evidence rating of very low and low, respectively when 4 studies were pooled. In comparison, ultrasound demonstrated a sensitivity ranging from 14%-96% (low certainty of evidence) and a specificity of 99%-100% in 2 studies (moderate certainty of evidence), while magnetic resonance urography demonstrated a sensitivity of 83% and specificity of 86% in 1 study with a low certainty of evidence. In a limited data set for each individual imaging modality, computed tomography urography appears the most sensitive imaging modality for the diagnostic evaluation of microhematuria. Future studies will be needed to evaluate the clinical and health system financial impacts of the change in guideline recommendations from computed tomography urography to renal ultrasound in evaluating low and intermediate risk patients with microhematuria.

Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder

BackgroundWith the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer.MethodsThe expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically.ResultsIn UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle.ConclusionsLow expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.

Preoperative nomogram integrating determinants of endoscopic management in upper urinary tract carcinoma

Preoperative nomogram integrating determinants of endoscopic management in upper urinary tract carcinoma

Preživljavanje pacijenata sa urotelnim karcinomom gornjeg urinarnog trakta nakon radikalne nefroureterektomije

Introduction: Identifying prognostic factors is essential for proper postoperative patient monitoring with upper urinary tract carcinoma, that would contribute to the decision-making process regarding the application of adjuvant chemotherapy after radical nephroureterectomy. Aim: To investigate demographic, clinical, and pathological prognostic factors of cancer-specific survival (CSS) for upper urothelial tumors. Methods: A retrospective cohort study was conducted including 342 patients who underwent radical nephroureterectomy. Kaplan-Meier method and LogRank test were used to assess survival. Cox regression analysis was used to determine the impact of different factors on cancer-specific survival after radical nephroureterectomy. Results: The study cohort consisted of 342 patients, with a mean follow-up time after radical nephroureterectomy of 32.5 (6-154) months. The 5-year CSS was 64% for this patient cohort. During the follow-up period, a total of 128 (37.4%) patients died, including 92 (28.2%) patients who died due to urothelial carcinoma. Multivariate analysis showed that the pathological stage of the primary tumor (HR, 11.1; 95% CI 3.64-33.8; P=0.001), presence of positive lymph nodes (HR, 2.04; 95% CI 1.05-3.94; P=0.03) and preoperative anemia (HR, 3.50; 95% CI 2.02-6.08; P=0.001) were independent predictors significantly associated with worse CSS. Patients with disease stage ≤ pT2 had significantly better CSS compared to patients with disease stage ≥ pT3 (P=0.001, Log-Rank test). The average CSS for patients with positive lymph nodes (pN+) was 22.1 ± 5.1 months (95% confidence interval from 12.1-32.2). Conclusion: Preoperative anemia, pathological disease stage, and presence of positive lymph nodes are significant independent prognostic predictors of CSS in patients who underwent radical nephroureterectomy (RNU).

Cause of death during upper tract urothelial carcinoma survivorship: A contemporary, population-based analysis.

Very few studies have been published on the causes of death of upper tract urothelial carcinoma (UTUC). We sought to explore the mortality patterns of contemporary UTUC survivors. We performed a retrospective cohort study involving patients with upper urinary tract carcinoma from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (2000 and 2015). We used standardized mortality ratios (SMRs) to compare death rates among patients with UTUC in the general population and excess absolute risks (EARs) to quantify the disease-specific death burden. A total of 10,179 patients with UTUC, including 7,133 who died, were included in our study. In total, 302 (17.17%) patients with the localized disease died of UTUC; however, patients who died from other causes were 4.8 times more likely to die from UTUC (n = 1,457 [82.83%]). Cardiovascular disease was the most common non-cancer cause of death (n = 393 [22.34% of all deaths]); SMR, 1.22; 95% confidence intervals [CI], 1.1-1.35; EAR, 35.96). A total of 4,046 (69.99%) patients with regional stage died within their follow-up, 1,413 (34.92%) of whom died from UTUC and 1,082 (26.74%) of whom died from non-cancer causes. UTUC was the main cause of death (SMR, 242.48; 95% CI, 230-255.47; EAR, 542.47), followed by non-tumor causes (SMR, 1.18; 95% CI, 1.11-1.25; EAR, 63.74). Most patients (94.94%) with distant stage died within 3 years of initial diagnosis. Although UTUC was the leading cause of death (n = 721 [54.29%]), these patients also had a higher risk of death from non-cancer than the general population (SMR, 2.08; 95% CI, 1.67-2.56; EAR, 288.26). Non-UTUC deaths accounted for 82.48% of UTUC survivors among those with localized disease. Patients with regional/distant stages were most likely to die of UTUC; however, there is an increased risk of dying from non-cancer causes that cannot be ignored. These data provide the latest and most comprehensive assessment of the causes of death in patients with UTUC.

Urine Cellular DNA Point Mutation and Methylation for Identifying Upper Tract Urinary Carcinoma.

Simple SummaryIt’s difficult to detect upper tract urothelial carcinoma at early stage. Invasive testing may increase risk of cancer recurrences in the bladder after radical nephroureterectomy. Thus, in the present study, we incorporated two-gene mutation and methylation biomarkers to conduct the diagnostic tool of upper tract urothelial carcinoma and performed external validation to investigate the utility and stability of the optimal panel. It showed a highly specific and robust performance. It may be used as a replaceable approach for early detection of upper tract urothelial carcinoma, resulting in less extensive examinations in patients at low risk. Background: To improve the selection of patients for ureteroscopy, avoid excessive testing and reduce costs, we aimed to develop and validate a diagnostic urine assay for upper tract urinary carcinoma (UTUC). Methods: In this cohort study we recruited 402 patients from six Hunan hospitals who underwent ureteroscopy for hematuria, including 95 patients with UTUC and 307 patients with non-UTUC findings. Midstream morning urine samples were collected before ureteroscopy and surgery. DNA was extracted and qPCR was used to analyze mutations in TERT and FGFR3 and the methylation of NRN1. In the training set, the random forest algorithm was used to build an optimal panel. Lastly, the Beijing cohort (n = 76) was used to validate the panel. Results: The panel combining the methylation with mutation markers led to an AUC of 0.958 (95% CI: 0.933–0.975) with a sensitivity of 91.58% and a specificity of 94.79%. The panel presented a favorable diagnostic value for UTUC vs. other malignant tumors (AUC = 0.920) and UTUC vs. benign disease (AUC = 0.975). Furthermore, combining the panel with age revealed satisfactory results, with 93.68% sensitivity, 94.44% specificity, AUC = 0.970 and NPV = 98.6%. In the external validation process, the model showed an AUC of 0.971, a sensitivity of 95.83% and a specificity of 92.31, respectively. Conclusions: A novel diagnostic model for analyzing hematuria patients for the risk of UTUC was developed, which could lead to a reduction in the need for invasive examinations. Combining NRN1 methylation and gene mutation (FGFR3 and TERT) with age resulted in a validated accurate prediction model.

Cutaneous metastases from an upper urinary tract carcinoma: A unusual entity and a poor prognosis

We report the case of a 58-year-old male with a history of diabetes who presented with a macroscopic hematuria. On physical examination, he was afebrile. Investigations revealed an anemia. A CT scan showed a tumor of the bladder and upper excretory system with multiple lung, spleen and liver metastases. The patient received blood transfusions and a trans-urethral resection of the tumor was performed. The patient’s condition later deteriorated and skin lesions appeared on the back and the scalp. A biopsy of the lesions confirmed their metastatic nature. The patient’s condition deteriorated and he died 4 weeks later.

Massive Hydronephrosis, Countless Lithiasis and Upper Urinary Tract Carcinoma

A 51-year-old otherwise healthy man presented to the emergency department with a 6-month history of weight loss, asthenia, lumbar pain and hematuria. Urinalysis was notable for hematuria without significant pyuria. Hemoglobin was 10.3 g/dL and serum creatinine was 1.2 mg/dL. The remainder of the complete blood count, metabolic panel, and coagulation parameters were normal. An abdominal x-ray was done (Figure 1) and based on the findings of this a computed tomography scan was performed (Figure 2).

De Ritis Ratio (Aspartate Transaminase/Alanine Transaminase) as a Significant Prognostic Factor With Upper Urinary Tract Carcinoma Who Underwent Radical Nephroureterectomy and Adjuvant Chemotherapy

Purpose: To investigate the correlation between preoperative De Ritis ratio (aspartate transaminase [AST]/alanine transaminase [ALT]) and postoperative clinical outcome in patients with upper urinary tract carcinoma (UTUC) who underwent radical nephroureterectomy (RNU) and adjuvant chemotherapy (ACH).Materials and Methods: We respectively analyzed the clinical and pathological data of 102 patients who underwent RNU and ACH for UTUC. Patients were divided into 2 groups, according to the optimal value of AST/ALT ratio. The effect of the AST/ALT ratio was analyzed by the Kaplan-Meier method and Cox regression hazard models for patients’ cancer-specific survival (CSS) and overall survival (OS).Results: Mean survival time was 50.5±41.2 months. Mean age was 61.4±9.7years. Forty-one of the patients (46.5%) were in the high AST/ALT group. According to receiver operating characteristic analysis, the optimal AST/ALT ratio was 1.2. In Kaplan-Meier analyses, the high AST/ALT group showed worse outcomes in OS (p=0.007) and CSS (p=0.011). Using Cox regression models of clinical and pathological parameters to predict OS, high AST/ALT ratio (hazard ratio [HR], 5.428; 95% confidence interval [CI]; 1.803–16.334; p=0.002), pathological T3 (pT3) or higher (HR, 1.464; 95% CI; 1.156-1.857; p=0.002), and to predict CSS, high AST/ALT ratio (HR, 4.417; 95% CI; 1.545–12.632; p=0.005), and pT3 or higher (HR, 1.475; 95% CI; 1.172–1.904; p=0.002) were determined as independent prognostic factors.Conclusions: Pretreatment AST/ALT ratio is a significant independent predictor of CSS and OS in advanced UTUC patients receiving systemic ACH after RNU.

Is robotic radical nephroureterectomy a safe alternative to open approach: The first prospective analysis.

To test the efficacy and safety profile of robotic radical nephroureterectomy compared to the open approach. We enrolled 45 consecutive patients who suffered from non-metastatic, upper urinary tract urothelial carcinoma from September 2019 to March 2021 and underwent radical nephroureterectomy. Patients were divided in two groups: group A consisted of 29 patients (open approach) and group B consisted of 16 patients (robotic approach). The factors which were taken into consideration were age, sex, body mass index, tumour size, side and grade, cancer stage, ASA score, operation time, drain removal time, foley time, hospitalization time, estimated blood loss, surgical margins, preoperative and postoperative creatinine, Hct and bladder recurrences. Statistical analysis was performed with the use of SPSS version 26 and p < 0.05 was the cut-off for reaching statistical significance. The mean age in group 1 was 67.12 years and in group 2 68.12 years, whereas the mean body mass index (BMI) in group 1 was 26.54 kg/m2 and in group 2 25.20 kg/m2. Operative time was better in group A (124 vs 186 mins p < 0.001) and estimated blood loss were better in group B compared to group A (137 vs 316 ml p < 0.001). Length of stay (LOS) was significantly less in the robotic group (5.75 vs 4.3 days p = 0.003) and the same applied for time required for drain removal (4.5 vs 3.3 days p = 0.006). Robotic radical nephroureterectomy is a safe and efficient alternative to open approach. It provides a favorable perioperative profile in patients suffering from upper urinary tract carcinoma without metastasis.

Management of the Distal Ureter During Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Comprehensive Review of Literature.

Radical open nephroureterectomy (ONU) with bladder cuff excision (BCE) is the traditional gold standard approach for management of high-risk non-metastatic upper tract urothelial cancer. ONU involves two separate procedures; the nephrectomy and distal ureterectomy, with each of these parts being able to be performed with an open or minimally-invasive approach. Multiple approaches have been described for the resection of the distal ureter and bladder cuff after mobilization of the kidney and upper ureter. A Medline search of the literature including relevant articles up to March, 2020 was performed. Search terms included "nephroureterectomy", "upper tract urothelial carcinoma", "upper urinary tract carcinoma OR UTUC", "open OR conventional OR ONU OR conventional", "robotic-assisted nephroureterectomy OR RANU", "laparoscop* OR LNU OR LRNU" and "minimally-invasive nephroureterectomy". Original articles, case series and review articles were included. There are no randomised studies. Various techniques have been described to manage the distal ureter during nephroureterectomy. This review provides an overview of these techniques. The perioperative and oncological outcomes following open versus endoscopic techniques and minimally invasive techniques have been described. Although endoscopic approaches have more favourable perioperative outcomes, this comes at the expense of increased risk of tumour spillage and recurrence compared to the traditional open approaches. Minimally-invasive techniques (laparoscopic and robotic-assisted NU) largely have superior perioperative outcomes versus their open NU counterparts, with comparable oncological outcomes. Current non-randomised evidence is open to selection bias and is insufficient to support or refute endoscopic management of the distal ureter as an alternative to open bladder cuff excision. The optimal approach to nephroureterectomy and management of the distal ureter continues to remain a surgical dilemma.

Urothelial cancer: population-based analysis of the problem in Ukraine

The aim of this work was to conduct a population analysis on the basis of the National Cancer Registry with the primary goal: to determine the effectiveness of urothelial cancer treatment in Ukraine; and the secondary goal: to identify the main trends and approaches to therapy with an assessment of their impact on overall survival. Materials and methods. The design of the study was retrospective observational. The analysis was conducted based on the data of the National Cancer Registry from 2008 to 2020. A total of 12,698 patients with urothelial tumors of the upper urinary tract and bladder who underwent surgical treatment were analyzed. Statistical sampling was performed based on the creation of the most homogeneous groups of patients with bladder cancer (BC) and the upper urinary tract carcinoma (UUTc) who had the required number of notified parameters for further analysis. The primary objectives of the analysis were to determine: the average age of primary detection of the studied nosologies, level of detection depending on gender, frequency of diagnosis verification before surgery, extent of surgery, frequency of postoperative complications based on data on 30-day rehospitalization, the level of deviation of the principles for prophylactic medical patients’ examination from generally accepted recommendations. The secondary objective was to assess the cumulative survival of patients with urothelial tumors depending on the localization of the primary tumor and the type of surgery (organ-sparing or radical). Results. Organ-sparing treatment was more typical for BC, while radical treatment was performed in 15 % of patients with carcinomas. Organ-sparing treatment was more typical for UUTc (40%). It should be noted that in this nosology it is acceptable for invasive forms of urothelial cancer. The level of 30-day hospitalization was low in both pathologies, with a slightly greater advantage of UUTc. The level of complications is grade III according to the Clavien-Dindo classification, averaging 0.2 % for the entire pool of patients. For BC, the overall survival rates by stages were: I — 73%, II — 49 %, III — 18 % and IV — 11 % (chi-square=1,807.207; p= 0.000001). For UUTc, the levels of 5-year overall survival correspond to the literature data, but there is a significant negative tendency to decrease the latter after a 10-year period for all stages (chi-square = 146.298; p = 0.000003). In Ukraine, organ-sparing treatment for UUTc was not inferior to radical nephroureterectomy in the context of 5-year survival (51.3 vs. 51%; log-rank test). The obtained data testify in favor of the 15% advantage of the total survival of patients who underwent radical nephroureterectomy at the premises of the National Cancer Institute (high volume center), compared to other regions of Ukraine. Levels of 5- and 10-year survival in both nosologies were characterized by a statistically non-significant advantage of UUTc over BC of 7 %. Conclusions. Superficial and locally advanced tumors are the most complex ones in the treatment of urothelial cancer of the bladder and upper urinary tract in Ukraine. Superficial tumors require the most radical surgeries and subsequent effective local treatment. Locally advanced tumors require a comprehensive approach to treatment, adequate systemic therapy influences the final indicators of overall survival. In cases of surgical resectability and preservation of renal function, UUTc requires organ-sparing treatment; this approach aims to increase creatinine clearance in patients before systemic chemotherapy and to reduce the likelihood of progression of comorbidities and associated mortality.

26: Role of Adjuvant Radiotherapy in the Management of Urothelial Carcinoma of Upper Urinary Tract –– A Systematic Review

26: Role of Adjuvant Radiotherapy in the Management of Urothelial Carcinoma of Upper Urinary Tract –– A Systematic Review

Bacillus Calmette-Guérin Perfusion Treatment via Cutaneous Ureterostomy for Carcinoma in Situ of the Upper Urinary Tract

Introduction: Bacillus Calmette-Guérin instillation is an established therapy for the treatment of carcinoma in situ of the upper urinary tract. Case Presentation: A 72-year-old woman underwent radical cystectomy with cutaneous ureterostomy for invasive bladder cancer with carcinoma in situ of both ureters. For the treatment of upper urinary tract carcinoma in situ, an infusion of 40 mg bacillus Calmette-Guérin through each ureterostomy was performed once weekly for 5 times. Urine cytology of the left upper urinary tract became negative, with a recurrence-free survival of 4 months. On the other hand, the right upper urinary tract became temporarily negative but turned positive after 3 months. Conclusion: Bacillus Calmette-Guérin perfusion therapy via cutaneous ureterostomy is considered as one of the useful therapies for carcinoma in situ of the upper urinary tract. Furthermore, there are several factors to be discussed, including the treatment duration, dosage and secondary therapeutic options.

Accuracy of an urine-based liquid biopsy genetic test in detecting renal pelvic cancer.

e16500 Background: Renal pelvis cancer is accounting for about two-thirds of upper tract urinary carcinoma. Lesions in renal pelvis often lead to a differential diagnosis that requires ureteroscopic biopsy. Besides causing discomfort and pain, ureteroscopy prior to surgery increases risk of tumor implantation and recurrence. Although urine cytology and FISH were applied, more effective non-invasive diagnostic method is imperative for diagnosis of renal pelvic cancer. Methods: A total of 141 patients with one or more lesions in renal pelvis detected by ultrasound were enrolled. 50-ml first-void urine sample was collection before ureteroscopic biopsy and was analysis by Genetron uro-18 genes panel, by which mutations in 17 genes and methylation status of ONECUT2 were analysis using high-throughput sequencing. If mutations and/or ONECUT2 methylation were detected in urine sediment DNA, the patients were considered as high risk of renal pelvis cancer. The results of the urine-based liquid biopsy genetic test were compared with pathology report and urine FISH results of urinary cells. Results: According to pathological analysis with ureteroscopic biopsy, 42 out of 141 patients (29.7%) were diagnosis with renal pelvic cancer: 13 low-grade, 24 high-grade, 5 equivocal. For 33 renal pelvic cancer patients with FISH testing result of urinary cells, only 54.5% (18/33) samples were positive. By Genetron uro-18 genes test, 95 patients (67.4%) were classified as high risk and 46 (32.6%) patients were low risk. The overall specificity was 88.0% (88/95) and overall sensitivity was 92.9% (39/42), which is significant higher than FISH test of urinary cells. Conclusions: With high specificity and sensitivity, Genetron uro-18 genes test could be incorporated in renal pelvic cancer diagnosis, especially for patients with a ultrasound detectable lesions. Ureteroscopy prior to surgery could be reduced, which may lead to decrease risk of tumor implantation and recurrence.