Diagnosis Of Upper Tract Urothelial Carcinoma Research Articles

Upper tract urothelial carcinoma: epidemiology, presentation, and high-risk endemic populations.

Upper tract urothelial carcinoma (UTUC) only accounts for 5-10% of all urothelial cancers but these patients present with high stage disease and 2 out of 3 patients have evidence of muscle-invasion at time of diagnosis. Furthermore, 10% of UTUC patients have associated Lynch syndrome and therefore diagnosis of UTUC should prompt timely evaluation and familial counseling. The purpose of this review is to outline the current evidence on the epidemiology, presentation, and high-risk endemic populations of UTUC through review of contemporary publications occurring over the preceding 18 months. Both the American Urological Association (AUA) and European Association of Urology (EAU) have published updated guidelines within the last 18 months for the management of UTUC. Of note, the updated guidelines give special consideration to identifying patients with risk factors for Lynch syndrome and recommend universal histologic testing for those with high probability of having Lynch syndrome cancers as well as referral for genetic counseling and germline testing. UTUC is an overall rare malignancy but tends to present with advanced stage and muscle-invasion. A proper understanding of the epidemiology, presentation, and high-risk endemic populations is necessary to develop preventive and interventional strategies.

Upper Tract Urothelial Carcinoma (UTUC): Prevalence, Impact and Management Challenge.

Upper tract urothelial carcinoma (UTUC) is an aggressive and difficult malignancy to treat. Owing to its rarity and the lack of specific high-level data, management mirrors that of urothelial cancer of the bladder (UCB). Over the past decade, UTUC has shown minimal improvement in survival rates. Its location makes the diagnosis and staging of UTUC more complex. Moreover, surgery often leads to a decline in renal function, rendering a proportion of patients ineligible for cisplatin. There is debate as to how best manage locally advanced UTUC perioperatively. Although immune checkpoint inhibitors (ICIs) have changed the treatment landscape for UCB, the response to ICIs in UTUC has been variable. With new technologies, our understanding of the molecular biology of UTUC has grown, helping to identify key molecular differences from UCB. This review summarises the evidence available on UTUC as a disease entity, discusses treatment in perioperative and metastatic settings, and considers future directions for the management of patients diagnosed with UTUC.

Upper Tract Urothelial Cancer: Guideline of Guidelines.

Upper tract urothelial carcinoma (UTUC) is a rare disease with a potentially dismal prognosis. We systematically compared international guidelines on UTUC to analyze similitudes and differences among them. We conducted a search on MEDLINE/PubMed for guidelines related to UTUC from 2010 to the present. In addition, we manually explored the websites of urological and oncological societies and journals to identify pertinent guidelines. We also assessed recommendations from the International Bladder Cancer Network, the Canadian Urological Association, the European Society for Medical Oncology, and the International Consultation on Bladder Cancer, considering their expertise and experience in the field. Among all the sources, only the American Urologist Association (AUA), European Association of Urology (EAU), and the National Comprehensive Cancer Network (NCCN) guidelines specifically report data on diagnosis, treatment, and follow-up of UTUC. Current analysis reveals several differences between all three sources on diagnostic work-up, patient management, and follow-up. Among all, AUA and EAU guidelines show more detailed indications. Despite the growing incidence of UTUC, only AUA, EAU, and NCCN guidelines deal with this cancer. Our research depicted high variability in reporting recommendations and opinions. In this regard, we encourage further higher-quality research to gain evidence creating higher grade consensus between guidelines.

Large-scale Prospective Validation Study of a Multiplex RNA Urine Test for Noninvasive Detection of Upper Tract Urothelial Carcinoma

BackgroundCurrent approaches for diagnosis and monitoring of upper tract urothelial carcinoma (UTUC) are often invasive, costly, and not efficient for early-stage and low-grade tumors. ObjectiveTo validate a noninvasive urine-based RNA test for accurate UTUC diagnosis. Design, setting, and participantsUrine samples were prospectively collected from 61 patients with UTUC and 99 controls without urothelial carcinomas, in five clinical centers between October 2022 and August 2023 prior to any invasive test (cystoscope or ureteroscope) or treatment. All samples were analyzed with a urine-based RNA test composed of eight genes (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2, and SWINGN). The test results were presented with a risk score for each participant, which was applied to categorize patients into low- or high-risk groups. Outcome measurements and statistical analysisThe diagnosis of UTUC was based mainly on preoperative radiological examination criteria and confirmed by postoperative pathological results. The recursive feature elimination and support vector machine algorithms, χ2, and Student t test were used. Results and limitationsThe eight-gene urine test accurately detected UTUC patients and controls with an area under the curve (AUC) of 0.901 in a single-center testing cohort (n = 93) and an AUC of 0.926 in a multicenter clinical validation cohort (n = 66). In the merged validation cohort, the eight-gene urine test achieved high sensitivity of 90.16%, specificity of 88.89%, and overall accuracy of 89.38%. Remarkably, excellent performance was achieved in 11 low-grade UTUC patients with accuracy of 100%. However, this study collected the urine of UTUC patients only at a single preoperative time point and did not perform continuous tests during the pathological process of UTUC in the surveillance population. ConclusionsOur results demonstrated that the eight-gene urine test can differentiate accurately between UTUC and other urological diseases with high sensitivity and specificity. In clinical practice, it may be used for identifying UTUC patients effectively, leading to reduced reliance on ureteroscopy and blind surgery. Patient summaryIn this study, we investigated a multiplex RNA urine test for noninvasive upper tract urothelial carcinoma (UTUC) diagnosis before treatment. We found that the risk scores derived from the multiplex RNA urine test differed significantly between UTUC patients and corresponding controls.

Diagnostic Value of Urine Cytology in Pharmacologically Forced Diuresis for Upper Tract Urothelial Carcinoma Diagnosis and Follow-Up.

We performed a urine cytology analysis of a pharmacologically induced diuresis for the diagnosis of upper tract urothelial carcinoma. To evaluate the diagnostic value of cytology of pharmacologically forced diuresis, an initial cohort of 77 consecutive patients with primary upper tract urothelial carcinoma treated via radical surgery was enrolled. To evaluate pharmacologically forced diuresis cytology as a follow-up procedure, a second cohort of 1250 patients who underwent a radical cystectomy for bladder cancer was selected. In the first cohort, the sensitivity of cytology of pharmacologically forced diuresis in patients with invasive, high-grade, low-grade, and concomitant carcinoma in situ was 8%, 9%, 0%, and 14%, respectively. In the second cohort, cytology of pharmacologically forced diuresis was positive in 30/689 (4.3%) patients, in whom upper urinary tract recurrence was present in 21/30 (70%) of cases, and urethral recurrence was present in 8/30 (26%) of cases. As a follow-up tool, cytology of pharmacologically forced diuresis showed a sensitivity, specificity, and positive and negative predictive values of 60%, 99%, 70%, and 98%, respectively. Overall, as a diagnostic tool, the sensitivity of cytology of pharmacologically forced diuresis is slightly better in patients with invasive upper tract urothelial carcinoma and concomitant carcinoma in situ. As a follow-up method, positive cytology of pharmacologically forced diuresis is strongly related to cancer recurrence and can reveal urethral recurrence. Cytology of pharmacologically forced diuresis might be useful in cases with contraindications for imaging or when achieving endoscopic access to the upper urinary tract is difficult.

Defining molecular features associated with microsatellite instability and response to immune checkpoint blockade in urothelial carcinoma.

536 Background: Microsatellite instability (MSI) and deficient mismatch repair (dMMR) are associated with sensitivity to immune checkpoint blockade (ICB) in urothelial carcinoma (UC). MSI status may only partially explain this sensitivity, and the molecular features that distinguish MSI-high (MSI-H) UC are not well described. Methods: Retrospective review of UC patients having undergone targeted exome sequencing of up to 505 genes was performed. Using the previously validated MSIsensor score, we identified MSI-H (score ≥10) and MSI stable (MSS) (score <3) UC tumors. Tumor mutational burden (TMB) was quantified. Gene alterations enriched in MSI-H UC were evaluated using the false discovery method with q<0.05 considered statistically significant. Mutational process signatures (MPS) were characterized using COSMIC v3.3. Survival analysis was performed using the Kaplan-Meier method with Cox proportional-hazards to determine progression-free (PFS) and overall survival (OS) based on molecular features. Results: Targeted exome sequencing data were available for 3,811 UC specimens representing 2,608 patients, of which 471 carried a diagnosis of upper tract UC. Of the total, 60 (1.6%) MSI-H tumors from 55 (2.1%) patients were identified. Germline testing (n=52) revealed dMMR mutations in 24 cases (46.2%) with MSH2 (59.6%) being most common. Median MSIsensor score was 19.8 (IQR 15.5, 27) and median TMB was 52.7 mut/Mb (IQR 39.7, 63.2). Notable gene alterations enriched in MSI-H tumors are summarized in Table 1. Dominant MPS in MSI-H UC included dMMR (85.0%), APOBEC (8.3%), and Aging (6.7%). MSI-H tumors clustered with dMMR mutational signatures SBS6 and SBS44. A total of 21 MSI-H and 160 MSS patients having received ICB for metastatic disease were identified for survival analysis. Median follow-up was 18.4 months (IQR 6.6, 58.5). MSI-H UC demonstrated superior PFS (HR 0.34, 95% CI 0.22-0.55) and OS (HR 0.48, 95% CI 0.28-0.80) following ICB. There was no association between TMB or MPS and survival following ICB in MSI-H UC. In MSS UC, TMB ≥10 mut/mB was associated with improved PFS (HR 0.56, 95% CI 0.40-0.79) and OS (HR 0.71, 95% CI 0.50-1.0). Conclusions: Targeted sequencing reveals distinct genomic features of MSI-H UC. The findings from this relatively large clinical cohort of MSI-H UC patients affirm previous associations between MSI status, TMB, and response to ICB in metastatic UC. [Table: see text]

Do Urine Cytology and FISH Analysis Have a Role in the Follow-Up Protocol of Upper Tract Urothelial Carcinoma?

BackgroundCurrent guidelines recommend a stringent follow-up regimen that includes interval cystoureteronephscopy, CT urography, and selective urine cytology sampling for upper tract urothelial carcinoma (UTUC) patients undergoing endoscopic treatment and management. There are no recommendations regarding FISH analysis. Our purpose was to assess the efficacy of cytology and FISH as part of the follow-up protocol and its significance to clinical decision-making in this scenario. MethodsThe medical records of all patients who managed endoscopically for UTUC at our institute between 2014 and 2022 were retrospectively analyzed. Demographic and clinical data, histology, cytology, and FISH results were collected. FISH analysis was considered malignant according to Paris criteria. ResultsDuring the study period, 62 patients underwent 561 ureteroscopies as part of the treatment and follow-up regimen of low-grade UTUC. Urine from the affected upper tract was sampled for cytology in 377 procedures, and FISH analyses were performed in 273. In 75.4% of FISH analyses, the result was different from the cytology results: FISH found malignant aberrations in 15.5% of cases where cytology was benign. Furthermore, FISH classified all the cells defined as atypical via cytology as either benign or malignant. In only one case (0.17%), the urinary cytology report changed the follow-up regimen. ConclusionCytology may be omitted from the follow-up protocol of low-grade UTUC. In the handful of cases cytology does assist the diagnosis of UTUC, there is an additional benefit to performing FISH analysis, particularly when cellular atypia is reported in the cytology results.

Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma

BackgroundThere is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor. MethodsIn this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated). ResultsGenomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue. ConclusionsSequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.

Diagnosis and Management of Non-Metastatic Upper Tract Urothelial Carcinoma: AUA/SUO Guideline

The purpose of this guideline is to provide a useful reference on the effective evidence-based diagnoses and management of non-metastatic upper tract urothelial carcinoma (UTUC). The Pacific Northwest Evidence-based Practice Center of Oregon Health & Science University (OHSU) team conducted searches in Ovid MEDLINE (1946 to March 3rd, 2022), Cochrane Central Register of Controlled Trials (through January 2022), and Cochrane Database of Systematic Reviews (through January 2022). The searches were updated August 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (Table 1).[Table: see text]Results:This Guideline provides updated, evidence-based recommendations regarding diagnosis and management of non-metastatic UTUC including risk stratification, surveillance and survivorship. Treatments discussed include kidney sparing management, surgical management, lymph node dissection (LND), neoadjuvant/adjuvant chemotherapy and immunotherapy. This standardized guideline seeks to improve clinicians' ability to evaluate and treat patients with UTUC based on available evidence. Future studies will be essential to further support these statements for improving patient care. Updates will occur as the knowledge regarding disease biology, clinical behavior and new therapeutic options develop.

PD46-06 UROLOGICAL FOLLOW-UP AND MUTATIONAL PATTERNS IN LYNCH SYNDROME PATIENTS: A SINGLE CENTER EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023PD46-06 UROLOGICAL FOLLOW-UP AND MUTATIONAL PATTERNS IN LYNCH SYNDROME PATIENTS: A SINGLE CENTER EXPERIENCE Pietro Scilipoti, Mattia Longoni, Chiara Re, Giuseppe Rosiello, Alessandro Bertini, Mario de Angelis, Giorgio Gandaglia, Eugenio Ventimiglia, Umberto Capitanio, Andrea Salonia, Francesco Montorsi, Alberto Briganti, and Marco Moschini Pietro ScilipotiPietro Scilipoti More articles by this author , Mattia LongoniMattia Longoni More articles by this author , Chiara ReChiara Re More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Alessandro BertiniAlessandro Bertini More articles by this author , Mario de AngelisMario de Angelis More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Eugenio VentimigliaEugenio Ventimiglia More articles by this author , Umberto CapitanioUmberto Capitanio More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , and Marco MoschiniMarco Moschini More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lynch Syndrome (LS) is a genetic dominant autosomal disease that predisposes to a broad spectrum of tumors, among which Upper Tract Urothelial Carcinoma (UTUC) is the third most common manifestation. We present the first results of our LS dedicated outpatient clinic with the aim of evaluating the incidence of UTUC, patterns of mutation and individuate the optimal follow up schemes among patients affected by LS. METHODS: We observed 23 LS patients from December 2021 to October 2022 at a tertiary referral center. We collected prospectively data regarding LS mutations, medical and family history and simultaneously started a strict follow up strategy. Genetic diagnosis was obtained both by Immunohistochemistry (IHC) and by genetic test (DNA sequencing). For each patient we applied Bethesda, EAU guidelines, Amsterdam I and II criteria. Follow up strategy was based on Ultrasound (US), urinalysis and urinary citology every two years. In high-risk cases (age >50 years, MSH2 mutation carriers and family history of UTUC) CT-scans where alternated with US every year in addition to urinary citology. RESULTS: Among this court 52.2% of patients (n=12) had a LS diagnosis after cancer manifestation, meanwhile 47.8% (n=11) through genetic counseling due to investigation in first degree relatives. Among our patient population, 8 patients (34.8%) had a diagnosis of colorectal cancer, 4 (17.4%) UTUC, 1 (4.3%) endometrial, 1 (4.3%) gastric, 1 (4.34%) skin cancer and 2 rare LS related cancer (Renal Clear Cell Carcinoma and Lung Cancer). MSH2 mutation was detected in 39.1% of cases (n=9), while MLH1 was found in 34.8% of cases (n=8). In subgroup analysis colorectal cancer's most common mutation was MSH2 (50%) followed by MLH1 (25%) and MSH6 (25%), while among UTUC cases, MSH2 was the most common (75%) and MLH1 was reported in 25% of cases. Median age at UTUC diagnosis was 60, while median age at colorectal cancer diagnosis was 49 (p=0.007). Bethesda and EAU guidelines criteria were more accurate (91% vs 90%) compared to Amsterdam I and II criteria (74%). No tumor diagnosis was made during the observational time. CONCLUSIONS: The current study is a first attempt to establish a dedicated LS outpatient clinic. This will let us observe the most frequent mutations, thus potentially in the future allow us to diagnose UTUC earlier and provide a refined follow up to LS patients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1172 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pietro Scilipoti More articles by this author Mattia Longoni More articles by this author Chiara Re More articles by this author Giuseppe Rosiello More articles by this author Alessandro Bertini More articles by this author Mario de Angelis More articles by this author Giorgio Gandaglia More articles by this author Eugenio Ventimiglia More articles by this author Umberto Capitanio More articles by this author Andrea Salonia More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Marco Moschini More articles by this author Expand All Advertisement PDF downloadLoading ...

PD46-02 BLOOD-BASED LIQUID BIOPSY FOR DIAGNOSIS AND SURVEILLANCE OF PRIMARY UPPER TRACT UROTHELIAL CARCINOMA: ROAD TO EMERGING NOVEL BIOMARKER

You have accessJournal of UrologyCME1 Apr 2023PD46-02 BLOOD-BASED LIQUID BIOPSY FOR DIAGNOSIS AND SURVEILLANCE OF PRIMARY UPPER TRACT UROTHELIAL CARCINOMA: ROAD TO EMERGING NOVEL BIOMARKER Alireza Ghoreifi, Stephanie Shishido, George Courcoubetis, Salmaan Sayeed, Amy Huang, Andrew Hung, Anne Schuckman, Monish Aron, Mihir Desai, Siamak Daneshmand, Inderbir Gill, Peter Kuhn, Jeremy Mason, and Hooman Djaladat Alireza GhoreifiAlireza Ghoreifi More articles by this author , Stephanie ShishidoStephanie Shishido More articles by this author , George CourcoubetisGeorge Courcoubetis More articles by this author , Salmaan SayeedSalmaan Sayeed More articles by this author , Amy HuangAmy Huang More articles by this author , Andrew HungAndrew Hung More articles by this author , Anne SchuckmanAnne Schuckman More articles by this author , Monish AronMonish Aron More articles by this author , Mihir DesaiMihir Desai More articles by this author , Siamak DaneshmandSiamak Daneshmand More articles by this author , Inderbir GillInderbir Gill More articles by this author , Peter KuhnPeter Kuhn More articles by this author , Jeremy MasonJeremy Mason More articles by this author , and Hooman DjaladatHooman Djaladat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Blood-based liquid biopsy has emerged as a novel diagnostic and prognostic biomarker in cancer patients, yet the efficacy of this test in patients with upper tract urothelial carcinoma (UTUC) is unknown. The aim of this study is to explore the feasibility of a liquid biopsy in the diagnosis and surveillance of primary UTUC. METHODS: In this prospective pilot study, under an IRB-approved protocol (#HS-19-00886), blood samples were collected between May 2021 and September 2022 from primary UTUC patients before surgical intervention with curative intent as well as follow-up visits. The samples were analyzed using the third generation comprehensive high-definition single cell assay (HDSCA3.0) to detect rare cells (e.g., circulating tumor cells [CTCs]) and other rare events (e.g., large extracellular vesicles [LEVs]) (Figure 1-A). The findings of pre-surgery liquid biopsies were compared to the blood samples of normal donors (NDs) who had no known pathology. Follow-up samples were compared to the baseline findings. RESULTS: A total of 22 UTUC patients and 50 NDs were included in the analysis. Pathologic staging of UTUC patients revealed 13 non-muscle invasive (<T2) and 9 muscle-invasive (≥T2) tumors. Most cases (17/22) were high-grade. Eight patients received neoadjuvant chemotherapy as well. HDSCA3.0 analysis indicated that rare cells were detectable in the peripheral blood collected from UTUC patients with a high heterogeneity. Total rare events and total rare cells detected in UTUC samples before surgery were significantly higher than that from the NDs. Similar trend was seen in other CTC and rare cell populations, including D|V, D|CK|V|CD, D|V|CD, D, D|CK, and total CK+cells as well as total LEVs and CK+only LEVs (Figure 1-B). Additionally, 11 follow-up samples, collected within a median 8 months following surgery, were available for the analysis that showed significant decrease in the incidence of total LEVs, CK LEVs, and CK|CD LEVs (Figure 1-C). Among these patients, there were 4 bladder recurrences but no distant metastasis. CONCLUSIONS: This study demonstrates promising evidence for the possible clinical utility of the liquid biopsy in UTUC. Rare cells and LEVs may be used in the diagnosis and surveillance of patients with UTUC. Source of Funding: USC Urology Research Council © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1169 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alireza Ghoreifi More articles by this author Stephanie Shishido More articles by this author George Courcoubetis More articles by this author Salmaan Sayeed More articles by this author Amy Huang More articles by this author Andrew Hung More articles by this author Anne Schuckman More articles by this author Monish Aron More articles by this author Mihir Desai More articles by this author Siamak Daneshmand More articles by this author Inderbir Gill More articles by this author Peter Kuhn More articles by this author Jeremy Mason More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement PDF downloadLoading ...

MP69-13 HOLMIUM:YAG VERSUS THULIUM:YAG LASER IN ENDOSCOPIC ABLATION OF UPPER TRACT UROTHELIAL CARCINOMA: A COMPARISON ON PERIOPERATIVE OUTCOMES AND SHORT-TERM FOLLOW-UP

You have accessJournal of UrologyCME1 Apr 2023MP69-13 HOLMIUM:YAG VERSUS THULIUM:YAG LASER IN ENDOSCOPIC ABLATION OF UPPER TRACT UROTHELIAL CARCINOMA: A COMPARISON ON PERIOPERATIVE OUTCOMES AND SHORT-TERM FOLLOW-UP Elena Morini, Davide Perri, Umberto Besana, Federica Mazzoleni, Andrea Pacchetti, Lorenzo Berti, Matteo Corinti, Maria Chiara Sighinolfi, Bernardo Rocco, Salvatore Micali, Javier Romero Otero, Jean Baptiste Roche, Antonio Luigi Pastore, and Giorgio Bozzini Elena MoriniElena Morini More articles by this author , Davide PerriDavide Perri More articles by this author , Umberto BesanaUmberto Besana More articles by this author , Federica MazzoleniFederica Mazzoleni More articles by this author , Andrea PacchettiAndrea Pacchetti More articles by this author , Lorenzo BertiLorenzo Berti More articles by this author , Matteo CorintiMatteo Corinti More articles by this author , Maria Chiara SighinolfiMaria Chiara Sighinolfi More articles by this author , Bernardo RoccoBernardo Rocco More articles by this author , Salvatore MicaliSalvatore Micali More articles by this author , Javier Romero OteroJavier Romero Otero More articles by this author , Jean Baptiste RocheJean Baptiste Roche More articles by this author , Antonio Luigi PastoreAntonio Luigi Pastore More articles by this author , and Giorgio BozziniGiorgio Bozzini More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Holmium-YAG (Ho:YAG) laser is the most widely used laser in urology for both the treatment of stones and soft tissues. However, the Thulium-YAG (Tm:YAG) laser has become a reliable alternative for soft tissue treatment. The aim of our study is to increase evidence on the safety and efficacy of endoscopic management of upper tract urothelial carcinoma (UTUC) with the Ho:YAG and Tm:YAG lasers. METHODS: 111 patients with a diagnosis of low-risk UTUC were enrolled. Exclusion criteria comprised patients with a bilateral or multifocal disease and use of antiplatelet/anticoagulant therapy. In all cases a preoperative computed tomography (CT) scan was performed with evidence of contrast-enhanced solid tissue inside the upper urinary tract. In all cases indication to ureteroscopy was given to confirm diagnosis and to perform biopsy. Endoscopic laser ablation was decided with respect to EAU guidelines recommendations: unifocal disease, tumor size <2 cm, negative or low-grade cytology, low-grade biopsy and no invasive aspect on CT. Laser ablation was performed with Tm:YAG and Ho:YAG in 62 (Group A, 55.9%) and 49 (Group B, 44.1%) patients respectively. Three months after surgery CT scan and ureteroscopy were performed. Afterwards, CT scan was performed every 6 months. RESULTS: Mean tumor size was 18.1 mm. Tumor was localised in the renal calyxes in 30 cases (27.0%), in the renal pelvis in 41 cases (37.0%) and inside the ureter in 40 cases (36.0%). Preoperative features were comparable between the two groups. Mean operative time was 18.2 min and 21.7 min in Groups A and B respectively (p=0.09). Mean haemoglobin drop at first postoperative day was 0.8 g/dl and 0.6 g/dl in Groups A and B (p=0.10). However, despite haemoglobin drop was not significantly different between the two treatments, a more consistent bleeding and a lower visibility were subjectively reported with the use of holmium laser. At a median follow-up of 42.3 months we observed a local recurrence in 12 patients (19.3%) in Group A and 18 (36.7%) patients in Group B (p=0.02). CONCLUSIONS: Despite perioperative outcomes were comparable between groups, a higher recurrence rate was observed after UTUC ablation with Ho:YAG laser. Lower intraoperative bleeding and better intraoperative vision were subjectively reported during surgery. These features along with a higher vaporisation effect with Tm:YAG laser may explain our results. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e969 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elena Morini More articles by this author Davide Perri More articles by this author Umberto Besana More articles by this author Federica Mazzoleni More articles by this author Andrea Pacchetti More articles by this author Lorenzo Berti More articles by this author Matteo Corinti More articles by this author Maria Chiara Sighinolfi More articles by this author Bernardo Rocco More articles by this author Salvatore Micali More articles by this author Javier Romero Otero More articles by this author Jean Baptiste Roche More articles by this author Antonio Luigi Pastore More articles by this author Giorgio Bozzini More articles by this author Expand All Advertisement PDF downloadLoading ...

The efficacy of ultrasonography for the detection of upper tract urothelial carcinoma

Ultrasonography and computed tomography urography are two commonly used modalities to image the upper tracts for the evaluation of hematuria. This study evaluated the efficacy of ultrasonography for the detection of upper tract urothelial carcinoma compared to computed tomography urography as a standard reference. This retrospective study included patients with urothelial carcinoma of the renal pelvis and/or ureter who were diagnosed using computed tomography urography and underwent surgical treatment. We calculated the sensitivity of ultrasonography in upper tract urothelial carcinoma diagnosis, further classified the degree of hydronephrosis on ultrasonography, and analyzed the relationship between the sensitivity and the degree of hydronephrosis and tumor location. Additionally, the usefulness of the combination of the screening ultrasonography findings, the presence of gross hematuria, and/or urine cytology was analyzed. This study included 136 patients with upper urothelial carcinoma. Ultrasonography in the diagnosis had 45.6% sensitivity, and ultrasonography findings, including the detection of hydronephrosis, were present in 72.8%. The presence of hydronephrosis and tumor location were associated with detection by ultrasonography. The tumor was identified in a total of 134 (98.5%) patients by combining tumor detection and hydronephrosis using ultrasonography with gross hematuria and positive urine cytology as screening. Ultrasonography showed acceptable sensitivity for upper tract urothelial carcinoma diagnosis. Considering the hydronephrosis findings, ultrasonography is a useful screening tool for upper tract urothelial carcinoma. Additionally, excessive computed tomography examinations can be reduced by adding gross hematuria and positive urine cytology.

Current methods facilitating diagnosis of upper tract urothelial carcinoma: a comprehensive literature review.

Currently, kidney-sparing surgeries are considered the preferred approach in low-risk tumours and in selected high-risk patients. Therefore, accurate diagnosis of UTUC is crucial for further management. The purpose of this review is to summarize available methods facilitating the diagnosis of upper tract urothelial carcinoma (UTUC). Recent articles propose numerous techniques of UTUC diagnosis. In this review, imaging, as well as, urine-based and endoscopic methods have been described and assessed. Regarding imaging, computed tomography urography remains a gold standard, while PET is superior in search for small lesions and nodal metastases. However, contrast-enhanced ultrasonography also shows promise. On the contrary, available urine tests, such as urinary cytology, fluorescent in-situ hybridization, Xpert, DNA methylation analysis, urine-based liquid biopsy, p16/Ki-67 dual immunolabelling, ImmunoCyt and NMP22 are either poorly researched, or not accurate enough to use solely. Finally, during ureterorenoscopy, photodynamic diagnosis and narrow-band imaging can facilitate proper visualization of the tumor. Endoluminal ultrasonography and confocal laser endomicroscopy can potentially improve staging and grading of UTUC. Also, the 'form tackle' biopsy should be performed using a basket in papillary lesions and cold-cup biopsy of flat or sessile lesions. Even though cryobiopsy shows promise in UTUC diagnosis, in-vivo studies are necessary before it is introduced into clinical practice.

Metformin is Associated with Better Survival Rate of Localized Upper Tract Urothelial Carcinoma Patients with Type 2 Diabetes

Purpose: Metformin, an antidiabetic drug, has been proposed to play a possible protective role in cancer recurrence and patient mortality. However, the exact mechanism and efficacy of metformin in urothelial cancer, especially upper tract urothelial carcinoma (UTUC), remain unknown. In this study, we conducted a population-based analysis to investigate whether metformin could improve the survival rate of patients with UTUC. Materials and Methods: Males ≥40 years diagnosed with UTUC were included in this retrospective population-based longitudinal cohort study. Data were collected from the registry of the Taiwan National Health Insurance database for patients with UTUC and type 2 diabetes mellitus (T2DM). Patients who had received at least two prescriptions of metformin were included in the study cohort as ever-users, and patients who had never used metformin were included in the control cohort as never-users. The hazard ratios (HRs) were calculated using Cox regression for ever-users and never-users. Results: Among the 781 enrolled patients, 439 and 342 patients were included as ever-users and never-users, respectively. The median survival time was 3.95 years in the never-user cohort compared to 6.90 years in the ever-user cohort, which remained statistically significant in both univariate and multivariate analyses (HR = 0.63 and 0.72, P = 0.0001 and 0.011, respectively). Furthermore, subgroup analysis showed that continuous usage of metformin before and after the diagnosis of UTUC was associated with a better survival in patients with UTUC (adjusted HR = 0.72, 95% confidence interval: 0.55–0.93). Conclusion: This study shows a relationship between metformin usage and better survival outcome in patients with localized UTUC. The result may contribute a favorable anticancer role of metformin in localized UTUC and suggests that continuous metformin usage improves all-cause mortality in patients with localized UTUC and T2DM.

The Impact of Surgical Waiting Time on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy: A Systematic Review.

Radical nephroureterectomy (RNU) with bladder cuff excision is a standard of care in patients with high-risk upper tract urothelial carcinoma (UTUC). Although several recommendations and guidelines on the delayed treatment of urologic cancers exist, the evidence on UTUC is scarce and ambiguous. The present systematic review aimed to summarize the available evidence on the survival outcomes after deferred RNU in patients with UTUC. A systematic literature search of the three electronic databases (PubMed, Embase, and Cochrane Library) was conducted until 30 April 2022. Studies were found eligible if they reported the oncological outcomes of patients treated with deferred RNU compared to the control group, including those patients treated with RNU without delay. Primary endpoints were cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). In total, we identified seven eligible studies enrolling 5639 patients. Significant heterogeneity in the definition of “deferred RNU” was found across the included studies. Three out of five studies reporting CSS showed that deferring RNU was associated with worse CSS. Furthermore, three out of four studies reporting OS found a negative impact of delay in RNU on OS. One out of three studies reporting RFS found a negative influence of delayed RNU on RFS. While most studies reported a 3 month interval as a significant threshold for RNU delay, some subgroup analyses showed that a safe delay for RNU was less than 1 month in patients with ureteral tumors (UT) or less than 2 months in patients with hydronephrosis. In conclusion, long surgical waiting time for RNU (especially more than 3 months after UTUC diagnosis) could be considered as an important risk factor having a negative impact on oncological outcomes in patients with UTUC; however, the results of the particular studies are still inconsistent. The safe delay for RNU might be shorter in specific subsets of high-risk patients, such as those with UT and/or hydronephrosis at the time of diagnosis. High-quality additional studies are required to establish evidence for valid recommendations.

Bladder Recurrence Following the Treatment of Upper Tract Urothelial Carcinoma

Objective: Although, upper tract urothelial carcinoma (UTUC) is rare it is associated with a high mortality rate and frequently, followed by bladder recurrence after radical surgery. Hence, this study aimed to identify the rate of bladder recurrence and its predictive factors.Material and Methods: We reviewed the medical records of 104 patients, who were diagnosed with UTUC and had radical nephroureterectomy (RNU), at the King Chulalongkorn Memorial Hospital. We excluded patients who have concurrent bladder cancer, or had a history of bladder cancer. Various clinicopathological factors were analyzed using the log-rank test and Cox proportional hazard model.Results: The mean age at diagnosis of UTUC was 68 years, and one-third of the patients were diagnosed with pathological T3 (33.7%). The mean follow-up duration was 56 months. Bladder recurrence occurred in 39 out of 104 patients (37.5%), and the median time to recurrence was 5.8 months (interquartile range 3.6 to 11.0 months). Tumor location in the distal ureter (p-value=0.038) and history of diagnostic ureteroscopy (p-value=0.004) were significantly associated with bladder recurrence in the univariate model. However, only the history of diagnostic ureteroscopy remained significant in the multivariate analysis (p-value=0.023).Conclusion: Bladder recurrence, following RNU, occurs in one-third of patients. Potential predictive factors may include history of diagnostic ureteroscopy, and the tumor location being in the distal ureter.

1191 The Use of CT Urography to Diagnose Upper Tract Urothelial Carcinomas (UTUC); Managing Surgical Resources During The COVID-19 Pandemic

Abstract Introduction Upper tract urothelial carcinomas (UTUC) account for 5-10% of urothelial malignancies. Rapid diagnosis is essential as 60% are invasive at diagnosis and confer poor prognoses. European Association of Urology (EAU) guidelines recommend CT urography (CTU) for initial diagnosis and staging of UTUCs. Diagnostic ureteroscopy (URS) is used second line where diagnosis is unclear. The COVID-19 pandemic has limited theatre access and may delay diagnosis of suspected UTUC. Our aim was to evaluate specific CTU findings in predicting UTUC to aid prompt diagnosis and risk stratification in a tertiary centre. Method A retrospective analysis was performed on 122 patients who underwent CTU with diagnostic URS over two years from 2018-2019 for possible UTUC. Data including demographics, imaging and histology were collected from our electronic database. Results 57 patients had confirmed UTUC, all had CT changes. CTU had an overall positive predictive value (PPV) of 45%. CT findings were divided into: hydronephrosis; filling defect/lesion; urothelial thickening; normal; or other. The PPV was highest for filling defects/lesions at 60%, hydronephrosis was 38%, urothelial thickening was 30%, and other was 33%. Of those with high-grade histology, 61% had evidence of filling defects/lesions and 24% had hydronephrosis. Conclusions A specific CTU finding of filling defect/lesion in combination with cytology can aid diagnosis and risk stratification of UTUC. This may enable us to reduce use of diagnostic URS, as well as associated risks of intravesical seeding, necessary in the COVID-19 pandemic. With other CTU findings of hydronephrosis or urothelial thickening, a diagnostic URS may be required.

1060 Upper Tract Urothelial Carcinoma (UTUC) – What Can We Learn from Historical Cases

Abstract Background UTUC has a poor prognosis with many patients presenting late, often without cardinal symptoms such as visible haematuria. Aims of this study were to assess presenting features, diagnostic tests and outcomes of patients with UTUC. Method Retrospective data collection was performed for patients diagnosed with UTUC (ureteric /renal) between Jan 2013-Dec 2017. Data was collected on demographics, presenting features, diagnostic tests, presence of concurrent bladder UC and outcome/survival. Results 67 patients were diagnosed with UTUC, 37 renal pelvis and 30 ureteric. The median age was 74 years (Range 49-90 years), M:F-2:1. 39 (58.2%) presented with haematuria, 1 having non-visible. 9 (13.4%) had loin pain, 4 (6.0%) systemic features (weight loss/lethargy), 15 (22.4%) other (detected on surveillance imaging, renal impairment). 61 had an USS of which 12 (19.7%) were normal and 49 demonstrated hydronephrosis or mass (80.3%). 21 (31.3%) had concurrent bladder UC. 9 (13.4%) prior to UTUC diagnosis (2 post cystectomy and 7 prior superficial UC) and 12 post diagnosis. 50 (74.6%) of UTUC were treated curatively with surgery and 17 (25.4%) palliated. The 2- and 5-year survival for those treated with curative intent was 79.9% and 58.5% compared to 31.25 and 7.5% for those treated with palliative intent. Conclusions Most patients with UTUC presented with visible hematuria, pain, or systemic features. USS has a high sensitivity, but cases will still be missed. The presence of prior bladder cancer is a significant risk factor and regular upper tract monitoring should be performed in high-risk patients (post-cystectomy, high-risk non muscle-invasive UC).

Stage and cancer-specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population-based study.

To examine the effect of specific Asian ethnic subgroups on stage at presentation and cancer-specific mortality in non-metastatic upper tract urothelial carcinoma among North American upper tract urothelial carcinoma Asian patients treated with radical nephroureterectomy. We relied on the Surveillance, Epidemiology and End Results database, from 2004 to 2016. Kaplan-Meier plots and multivariable Cox regression models predicting cancer-specific mortality were used. Of 584 upper tract urothelial carcinoma patients, 173 (29.6%) were Chinese versus 130 (22.3%) Japanese versus 68 (11.6%) Korean versus 64 (11.0%) Filipino versus 40 (6.8%) Vietnamese versus 109 (18.7%) other. Vietnamese and Chinese patients showed the highest rates of T4 N0 M0 and/or T1-4 N1-2 M0 (25.0% and 18.5%, respectively), relative to other Asian ethnic subgroups. In Kaplan-Meier plots, Vietnamese patients showed the highest cancer-specific mortality rate. In multivariable models, Vietnamese ethnicity also independently predicted higher cancer-specific mortality (hazard ratio 2.15, P=0.02 and hazard ratio 1.96, P=0.03), relative to Japanese and Chinese patients. All other Asian ethnic subgroups showed similar cancer-specific mortality patterns. Vietnamese and Chinese patients are at a stage disadvantage at upper tract urothelial carcinoma diagnosis, relative to all other Asian ethnicities. After adjustment for stage, only Vietnamese patients showed a survival disadvantage relative to all other Asian ethnic subgroups. As a result, it appears that Vietnamese patients not only present at a higher upper tract urothelial carcinoma stage, but additionally appear to harbor upper tract urothelial carcinoma that progresses at a faster rate than in other Asian ethnic subgroups.