Tract Urothelial Carcinoma Research Articles

The Impact of Non-Muscle-Invasive Recurrence of Upper Tract Urothelial Carcinoma on The Survival of Patients After Radical Nephroureterectomy

The Impact of Non-Muscle-Invasive Recurrence of Upper Tract Urothelial Carcinoma on The Survival of Patients After Radical Nephroureterectomy

The metastatic and advanced upper tract urothelial carcinoma-a separate entity or bladder cancer's younger sibling?

Upper tract urothelial carcinoma (UTUC) is acancer that is often already in an advanced stage at the time of initial diagnosis. Although urothelial carcinoma of the upper and lower urinary tracts both originate from the urothelium and have similar genetic alterations, there are significant differences in their distribution. In localized high-risk UTUC, radical nephroureterectomy is the gold standard therapy. In metastatic UTUC, major changes are emerging in sequential therapy due to the investigation of new classes of drugs. In addition to platinum-based combination chemotherapy and immunotherapy, new substances such as antibody-drug conjugates (ADCs) and FGFR inhibitors are used.

VJY35 If not now, then when? The need for new evidence in the robotic management of upper tract urothelial carcinoma. Current indications and video presentation by the Junior ERUS/Young Academic Urologist Working Group on Robot-assisted Surgery

VJY35 If not now, then when? The need for new evidence in the robotic management of upper tract urothelial carcinoma. Current indications and video presentation by the Junior ERUS/Young Academic Urologist Working Group on Robot-assisted Surgery

Retrograde transurethral injection of indocyanine green better assists complete transperitoneal nephroureterectomy in a single-position.

Complete transperitoneal nephroureterectomy (CTNU) in a single-position is an advanced surgical technique for the treatment of upper urinary tract urothelial carcinoma (UTUC), performed entirely through a transperitoneal approach without the need for patient repositioning. Indocyanine green (ICG) has been extensively studied in urologic surgery, with applications ranging from sentinel lymph node mapping to tumor localization. This study aimed to evaluate the performance of retrograde ureteral fluorescence imaging in CTNU. This retrospective cohort enrolled 81 patients diagnosed with UTUC and underwent single-position CTNU. Cohorts were divided into two groups according to whether the ICG was applied. Perioperative data and oncology outcomes were recorded and analyzed. In total, 81 eligible participants were finally included, with 40 in the ICG group and 41 in the non-ICG group. The ICG group presented significantly shorter ureter identification time (8.5±3.3 vs. 17.3±4.2 min, P<0.001) and duration of surgery (132±40 vs. 162±49 min, P=0.003), as well as lower estimated blood loss (EBL) (108±94 vs. 183±126 mL, P=0.003) compared to the non-ICG group. The rates of intravesical and extravesical carcinoma recurrence were comparable between the two groups. At a median follow-up of 16.7 months, there were no significant differences in terms of the recurrence-free survival (RFS) and overall survival (OS) between groups. ICG guided ureteral fluorescence imaging in single-position CTNU showed significant advantages in precisely and effectively locating the ureter, with improved surgical outcomes. Meanwhile, the enhanced visualization of the ureteral intramural segment and bladder cuff facilitated the complete removal of the specimen en bloc and the watertight closure of the bladder.

PE091 Laparoscopic radical nephroureterectomy with open bladder cuff excision vs. complete robotic approach for the treatment of upper urinary tract urothelial carcinoma: Our experience

PE091 Laparoscopic radical nephroureterectomy with open bladder cuff excision vs. complete robotic approach for the treatment of upper urinary tract urothelial carcinoma: Our experience

5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data

BackgroundIncreasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. MethodsThe MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. ResultsOverall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58–1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87–1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. ConclusionsThe use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

2017P Intrinsic molecular difference between bladder and upper tract urothelial carcinomas and its impacts in treatment response

2017P Intrinsic molecular difference between bladder and upper tract urothelial carcinomas and its impacts in treatment response

2018P Nephron-sparing surgery combined with perioperative systemic therapy in select high-risk upper tract urothelial carcinoma (UTUC) Patients: A pilot study for a prospective phase II trial

2018P Nephron-sparing surgery combined with perioperative systemic therapy in select high-risk upper tract urothelial carcinoma (UTUC) Patients: A pilot study for a prospective phase II trial

PE090 Radiomics-based CT urogram approach for the prediction of survival and recurrence in upper urinary tract urothelial carcinoma

PE090 Radiomics-based CT urogram approach for the prediction of survival and recurrence in upper urinary tract urothelial carcinoma

Blood-, Tissue- and Urine-Based Prognostic Biomarkers of Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) is a rare but aggressive neoplasm. Currently, there are few reliable and widely used prognostic biomarkers of this disease. The purpose of this study was to assess the prognostic value of blood-, tissue- and urine-based biomarkers in patients with UTUC. A comprehensive literature search was conducted using the PubMed, Cochrane and Embase databases. Case reports, editorials and non-peer-reviewed literature were excluded from the analysis. As a result, 94 articles were included in this review. We evaluated the impact of 22 blood-based, 13 tissue-based and 4 urine-based biomarkers and their influence on survival outcomes. The neutrophil-lymphocyte ratio, albumin, C-reactive protein, De Ritis ratio, renal function and fibrinogen, which are currently mentioned in the European Association of Urology (EAU) guidelines, are well researched and most probably allow for a reliable prognosis estimate. However, our review highlights a number of other promising biomarkers that could potentially predict oncological outcomes in patients with UTUC. Nonetheless, the clinical value of some prognostic factors remains uncertain due to the lack of comprehensive studies.

The grimacing face of adverse upper tract urothelial carcinoma can now POUT with adjuvant chemotherapy!

The grimacing face of adverse upper tract urothelial carcinoma can now POUT with adjuvant chemotherapy!

Liquid Biopsy-Based Accurate Diagnosis and Genomic Profiling of Hard-to-Biopsy Tumors via Parallel Single-Cell Genomic Sequencing of Exfoliated Tumor Cells.

Liquid biopsy provides a convenient and safer procedure for the diagnosis and genomic profiling of tumors that are inaccessible to biopsy by analyzing exfoliated tumor cells (ETCs) or tumor-derived cell-free DNA (cfDNA). However, its primary challenge lies in its limited accuracy in comparison to tissue-based approaches. We report a parallel single-ETC genomic sequencing (Past-Seq) method for the accurate diagnosis and genomic profiling of hard-to-biopsy tumors such as cholangiocarcinoma (CCA) and upper tract urothelial carcinoma (UTUC). For CCA, a prospective cohort of patients with suspicious biliary strictures (n = 36) was studied. Parallel single-cell whole genome sequencing and whole exome sequencing were performed on bile ETCs for CCA diagnosis and resolving mutational profiles, respectively, along with bile cfDNA sequenced for comparison. Concordant single-cell copy number alteration (CNA) profiles in multiple ETCs provided compelling evidence for generating a malignant diagnosis. Past-Seq yielded bile-based accurate CCA diagnosis (96% sensitivity, 100% specificity, and positive predictive value), surpassing pathological evaluation (56% sensitivity) and bile cfDNA CNA analysis (13% sensitivity), and generated the best performance in the retrieval tissue mutations. To further explore the applicability of Past-Seq, 10 suspicious UTUC patients were investigated with urine specimens, and Past-Seq exhibited 90% sensitivity in diagnosing UTUC, demonstrating its broad applicability across various liquid biopsies and cancer types.

Role of Chemoablation Using UGN-101 in Upper Tract Urothelial Carcinoma: A Systematic Review and MetaAnalysis of Available Evidence.

To examine the safety and efficacy of chemoablation using UGN-101 in patients with upper tract urothelial cancer (UTUC). We conducted a systematic search through 7 databases/registries to identify key observational and experimental studies reporting either the efficacy or safety of UGN-101 in UTUC patients regardless of the risk or grade of the disease. The outcomes included efficacy (complete/partial/no response, survival, death, recurrence, or progression) and safety endpoints. All meta-analyses were conducted through STATA. The prevalence rate and its 95% CI were pooled across studies. A subgroup meta-analysis was conducted on follow-up. The quality was assessed using the Newcastle Ottawa Scale. Twenty studies (1051 patients) were analyzed. Complete response was reported in 49% (39%-60%) of cases, and 5% (0%- 15%) had disease progression. Treatment cessation was reported in 13% (3%-27%) of patients. Four percent of cases needed radical nephroureterectomy. Recurrence and death occurred in 14% (7%-23%) and 6% (2%-10%) of patients. Complications occurred in 63% (39%-85%), the majority of which were of grades I, II, and III. Ureteral stenosis was the most common complication accounting for 35% of cases. Chemoablationrelated complications occurred more than procedure-related ones. Based on available evidence, the intracavitary instillation of UGN-101 gel provides an alternative therapeutic option for upper tract urothelial cancer. Chemoablation provides good clinical outcomes in terms of complete response, disease progression and recurrence, and the need to undergo nephroureterectomy. Complications were encountered in more than half the population; however, most of them were of low grades.

Central pathology review and its prognostic value in upper tract urothelial carcinoma patients: a nationwide multi-institutional study

The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.

Effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk upper tract urothelial carcinoma: a retrospective, real-world study.

Upper tract urothelial carcinoma (UTUC) is a rare subset of urothelial cancers with poor prognosis. No consensus exists on the benefit of adjuvant immunotherapy for patients with UTUCs after nephroureterectomy with curative intent and the existing studies are limited. Herein, this study aimed to evaluate the effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk UTUC. A retrospective study was conducted on 63 patients with high-risk UTUC who received tislelizumab with or without gemcitabine-cisplatin (GC) chemotherapy regimen after surgery between January 2020 and December 2022. Data on demographic and clinical characteristics, surgical, outcomes, prognostic factors, and safety were collected and analyzed. Among the 63 patients with high-risk UTUC, the median age was 66years (interquartile range 57-72), with 33 (52%) being male. The majority of patients with staged pT3 (44%) and pN0 (78%) disease. Fifty-one patients (81%) received tislelizumab plus GC chemotherapy, and 12 (19%) were treated with tislelizumab monotherapy. After the median follow-up of 26months (range 1-47), 49 (78%) patients achieved stable disease. The 2-year disease-free survival (DFS) and 2-year overall survival were 78.68% (95% CI: 60.02-87.07%) and 81.40% (95% CI: 68.76-89.31%), respectively. The cycles of GC chemotherapy were independent prognostic factors for survival, with higher DFS (hazard ratio = 0.68, 95% CI, 0.50-0.93; p = 0.016) observed in the subgroup undergoing ≥ 3 cycles versus < 3 cycles of GC chemotherapy. Fifty-eight patients (92%) experienced at least one treatment-related adverse event (TRAE), with grade 3-4 TRAEs occurring in 13%. The most common grade 3-4 TRAEs were decreased white blood cells, thrombocytopenia, and ulcers. The study demonstrates promising clinical benefits and a manageable safety profile of the tislelizumab-based adjuvant regimen for patients with high-risk UTUC. This suggests that adjuvant immunotherapy represents a potential therapeutic strategy for this population.

Exploring Radiotherapy as a Promising Alternative for Managing Advanced Upper Tract Urothelial Carcinoma: Rescuing Chemotherapy-Intolerant Patients

PurposeTo investigate the safety and effectiveness of radiotherapy for advanced upper tract urothelial carcinoma (UTUC) patients intolerant to chemotherapy. MethodsData for 21 patients with advanced UTUC intolerant to chemotherapy were retrospectively collected. All patients were treated with conventionally fractionated radiotherapy (50-70 Gy/20-33 f) or partial-SABR boost to the lesions (50-60 Gy/20-25 f with tumor center boosted with 6-8 Gy/f, 3-5 f) for bulky tumors. ResultsThe median age was 75 years (range, 58-87 years). Primary tumor resection was performed for all patients and none underwent metastatic resection. Seventeen (81%) patients had oligometastasis (1-5 metastases) at diagnosis. Eighteen (85.7%) received irradiation to all tumor lesions. Lymph node metastasis was predominant in the whole group (17/21). Other lesions were distributed as local recurrence (7/21), bone metastases (2/21) and abdominal wall/muscle (2/21). The median follow-up time was 38.5 months (interquartile range, 15.2-48.7 months). Rate of local control (LC), progression-free survival (PFS) and overall survival (OS) of the whole group at 1 year were 90%, 46.6%, and 80.4%, respectively. At 3 years, LC, PFS and OS were 65.6%, 26.6%, and 40.9%, respectively. Fourteen patients developed acute mild gastrointestinal toxicity, generally of grade 1-2; 8 patients developed acute grade 1-2 hematological toxicity, consisting mainly of anemia and leukopenia. No grade 3 or higher acute or late toxicities were observed. ConclusionFor patients with advanced UTUC who are not able to tolerate chemotherapy, radiotherapy is a safe treatment and can achieve good local tumor control.

Untethered Microgrippers for Biopsy in the Upper Urinary Tract.

Untethered microrobots offer the possibility to perform medical interventions in anatomically complex and small regions in the body. Presently, it is necessary to access the upper urinary tract to diagnose and treat Upper Tract Urothelial Carcinoma (UTUC). Diagnostic and treatment challenges include ensuring adequate tissue sampling, accurately grading the disease, achieving completeness in endoscopic treatment, and consistently delivering medications to targeted sites. This work introduces microgrippers (µ-grippers) that are autonomously triggered by physiological temperature for biopsy in the upper urinary tract. The experiments demonstratedthat µ-grippers can be deployed using standard ureteral catheters and maneuvered using an external magnetic field. The μ-grippers successfully biopsied tissue samples from ex vivo pig ureters, indicating that the thin-film bilayer springs' autonomous, physiologically triggered actuation exerts enough force to retrieve urinary tract tissue. The quality of these biopsy samples is sufficient for histopathological examination, including hematoxylin and eosin (H&E) and GATA3 immunohistochemical staining. Beyond biopsy applications, the µ-grippers' small size, wafer-scale fabrication, and multifunctionality suggest their potential for statistical sampling in the urinary tract. Experimental dataand clinical reports underscore this potential through statistical simulations that compare the efficacy of µ-grippers with conventional tools, such as ureteroscopic forceps and baskets.

Laparoscopic Versus Open Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-Analysis of Propensity-Score Matched Studies.

The effectiveness of laparoscopic nephroureterectomy (LNU) vs open nephroureterectomy (ONU) for upper tract urothelial carcinoma (UTUC) is unclear. We conducted a meta-analysis of studies based on propensity score-matched cohorts to compare the surgical and oncological outcomes of LNU and ONU in UTUC patients. A literature search was conducted on PubMed, Embase, and Cochrane Library until July 12, 2023. The Newcastle-Ottawa Scale was utilized to assess the quality of eligible studies. Measurements of surgical and oncological outcomes were extracted and pooled including mean difference (MD), risk ratio (RR), hazard ratios (HR), and 95% confidence intervals (CI). Five high-quality retrospective studies were included, totaling 6422 patients; 2080 (32.4%) underwent LNU, and 4342 (67.6%) underwent ONU. With respect to surgical outcomes, patients in the LNU group experienced less estimated blood loss and had shorter hospital stay than those in the ONU group, but there was no significant difference in complication rates and operation time. In regard to oncological outcomes, there were no significant differences between the LNU and ONU groups in 3-year overall survival (OS) and cancer-specific survival (CSS). However, 3-year intravesical recurrence free survival (IVRFS) was worse in the LNU group compared to the ONU group. LNU was associated with less estimated blood loss and shorter hospital stays than ONU, but there were no differences in OS and CSS between the surgical modalities. Nonetheless, LNU might result in poorer IVRFS than ONU.

The impact of double-J ureteral stenting before radical cystectomy on the development of upper tract urothelial carcinoma.

It is controversial whether the use of a double-J stent (DJ) in patients with bladder cancer before radical cystectomy (RC) increases the risk of tumour seeding in the upper tract and thus the risk of metachronous upper tract urothelial carcinoma (UTUC). The aim of our study is to investigate the risk of upper tract recurrence after RC in patients previously managed with a DJ stent. A total of 699 patients who had undergone RC between January 2003 and March 2022 with complete perioperative data and pathological outcome were included in our study. Patients treated preoperatively with a DJ stent were identified and compared for development of metachronous UTUC with those who did not receive prior internal stenting. Multivariable Cox regression analysis was used to determine predictors of UTUC occurrence among the possible pathological features; risk factors for mortality after RC were also examined. Of 699 patients, 117 (16.7%) were managed preoperatively with a DJ stent. The overall probability of metachronous UTUC was 1%, 4% and 6% at 1, 3 and 5 years, respectively. The groups with and without DJ stenting were comparable regarding their clinicopathologic features, except for the higher incidence of hydronephrosis in the DJ group. At similar follow-up periods (median follow-up 32 months), metachronous UTUC was detected in four (3.4%) patients in the DJ group and in 13 (2.2%) in the non-stented group (P=0.44). The median interval (IQR) from cystectomy to UTUC was 40.5 (20-49) months in the DJ group and 37 (24-82) in the non-stented group (P=0.7). In the multivariable analysis, only presence of CIS (HR 3.83, 95% CI 1.19-12.29, P=0.024) and positive ureteral margin (HR=5.2, 95% CI 1.38-19.57, P=0.015) were predictors of metachronous UTUC. The study is limited by the retrospective nature and relatively short follow-up. Ureteral stenting for management of hydronephrosis in patients with bladder cancer undergoing RC is a viable option, without higher risk for UTUC or mortality. Patients with positive ureteral margin and CIS are considered high-risk groups for upper tract recurrence and should receive long-term, rigorous follow-up.

No difference in oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving radical nephroureterectomy

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it’s necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.