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Hemo O, Hasdai T, Hendel H, Shvero A, Kleinmann N, Lifshitz D. Emerging strategies: conservative management of upper tract urothelial carcinoma. Curr Opin Urol 2025:00042307-990000000-00243. [PMID: 40275863 DOI: 10.1097/mou.0000000000001290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
PURPOSE OF REVIEW Upper tract urothelial carcinoma (UTUC) is a rare yet aggressive malignancy, representing 5-10% of urothelial cancers. While radical nephroureterectomy (RNU) has traditionally offered excellent oncological control, it compromises renal function. Recent advancements have shifted the paradigm toward kidney-sparing strategies in select cases. This review highlights innovations in UTUC diagnosis and conservative management, focusing on emerging imaging techniques, noninvasive biomarkers, and minimally invasive treatments. RECENT FINDINGS Advances in multiparametric MRI and radiomics have improved diagnostic accuracy and risk stratification. Moreover, noninvasive biomarkers - including circulating tumor DNA, microRNAs, and urinary methylation assays - provide promising tools for early detection and surveillance. Kidney-sparing approaches such as endoscopic laser ablation and segmental ureterectomy have demonstrated comparable oncologic outcomes in low-risk patients. Moreover, topical therapies, including intracavitary treatments like UGN-101, offer a promising minimally invasive option. SUMMARY The conservative management of UTUC is evolving, driven by advancements in imaging, molecular diagnostics, and minimally invasive treatments. While kidney-sparing approaches are increasingly utilized in low-risk patients, further prospective studies are needed to validate their efficacy.
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Affiliation(s)
- Orel Hemo
- Department of Urology, Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan
| | - Tomer Hasdai
- Department of Urology, Rabin Medical Center, Petach Tikva, Israel, affiliated to the Tel Aviv University faculty of medcine
| | - Hen Hendel
- Department of Urology, Rabin Medical Center, Petach Tikva, Israel, affiliated to the Tel Aviv University faculty of medcine
| | - Asaf Shvero
- Department of Urology, Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan
| | - Nir Kleinmann
- Department of Urology, Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan
| | - David Lifshitz
- Department of Urology, Rabin Medical Center, Petach Tikva, Israel, affiliated to the Tel Aviv University faculty of medcine
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Masson-Lecomte A, Birtle A, Pradere B, Capoun O, Compérat E, Domínguez-Escrig JL, Liedberg F, Makaroff L, Mariappan P, Moschini M, Rai BP, van Rhijn BWG, Shariat SF, Smith EJ, Teoh JYC, Soukup V, Wood R, Xylinas EN, Soria F, Seisen T, Gontero P. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: Summary of the 2025 Update. Eur Urol 2025:S0302-2838(25)00145-9. [PMID: 40118741 DOI: 10.1016/j.eururo.2025.02.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Accepted: 02/26/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND AND OBJECTIVE We present a summary of the 2025 update for the European Association of Urology (EAU) guidelines for upper urinary tract urothelial carcinoma (UTUC). The aim is to provide practical recommendations on the clinical management of UTUC with a focus on diagnosis, treatment, and follow-up. METHODS For the 2025 guidelines on UTUC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with UTUC. The guidelines stress the importance of appropriate treatment taking into account patient values and preferences. Key updates in the 2025 UTUC guidelines include: significant changes to the recommendations for UTUC diagnosis; complete revision of the sections addressing risk stratification, ureteroscopy, and the surgical approach for radical nephroureterectomy; addition of four new recommendations, two related to kidney-sparing management of localised low-risk UTUC and a further two related to management of high-risk nonmetastatic UTUC; a review and adaptation of recommendation for UTUC follow-up; and addition of a new section addressing quality indicators for UTUC management. CONCLUSIONS AND CLINICAL IMPLICATIONS This overview of the 2025 EAU guidelines on UTUC offers valuable insights into risk factors, diagnosis, classification, treatment, and follow-up for UTUC. The guidelines contain information on the management of individual patients according to the current best evidence and are designed for effective integration in clinical practice.
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Affiliation(s)
| | - Alison Birtle
- Rosemere Cancer Centre, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK; University of Manchester, Manchester, UK; University of Central Lancashire, Preston, UK
| | - Benjamin Pradere
- Department of Urology, UROSUD, La Croix Du Sud Hospital, Quint Fonsegrives, France
| | - Otakar Capoun
- Department of Urology, General University Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czechia
| | - Eva Compérat
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | | | - Fredrik Liedberg
- Institution of Translational Medicine, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden
| | - Lydia Makaroff
- Fight Bladder Cancer, Chinnor, UK; World Bladder Cancer Patient Coalition, Brussels, Belgium
| | - Paramananthan Mariappan
- Edinburgh Bladder Cancer Surgery, University of Edinburgh, Western General Hospital, Edinburgh, UK
| | - Marco Moschini
- Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Bhavan P Rai
- Department of Urology, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Bas W G van Rhijn
- Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
| | - Emma J Smith
- Guidelines Office, European Association of Urology, Arnhem, The Netherlands
| | - Jeremy Y C Teoh
- S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - Viktor Soukup
- Department of Urology, General University Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czechia
| | - Robert Wood
- Patient representative, European Association of Urology, Arnhem, The Netherlands
| | - Evanguelos N Xylinas
- Department of Urology, Bichat-Claude Bernard Hospital, AP-HP, Université de Paris, Paris, France
| | - Francesco Soria
- Department of Urology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy
| | - Thomas Seisen
- GRC 5 Predictive Onco-Uro, Sorbonne University, Paris, France; Department of Urology, Pitie-Salpetriere Hospital, AP-HP, Paris, France
| | - Paolo Gontero
- Department of Urology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy
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Gallioli A, Uleri A, Verri P, Tedde A, Mertens LS, Moschini M, Del Giudice F, Soria F, Laukhtina E, Subiela JD, Krajewski W, D'Andrea D, Mari A, Marcq G, Mori K, Teoh J, Afferi L, Albisinni S, Sanguedolce F, Palou J, Breda A, Pradere B. Oncologic Outcomes of Endoscopic Management of Upper Tract Urothelial Carcinoma: A Systematic Review and Pooled Analysis from the EAU-YAU Urothelial Working Group. Eur Urol Focus 2025:S2405-4569(25)00009-4. [PMID: 39894734 DOI: 10.1016/j.euf.2025.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 12/08/2024] [Accepted: 01/15/2025] [Indexed: 02/04/2025]
Abstract
BACKGROUND AND OBJECTIVE Data about the mid- and long-term oncologic outcomes of endoscopic kidney-sparing surgery (eKSS) for upper tract urothelial carcinoma (UTUC) are scarce. Therefore, we aimed to summarize the current evidence on the oncologic outcomes of eKSS for UTUC. METHODS A literature search was conducted to identify reports published until May 2024. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed to identify eligible studies. The outcomes were the following: recurrence-free (RFS), intravesical recurrence-free (IV-RFS), progression-free (PFS), cancer-specific (CSS), and overall (OS) survival. KEY FINDINGS AND LIMITATIONS We found 56 studies (n = 52 retrospective) that met our inclusion criteria (n = 2862 patients). The 1-, 2-, 5-, and 10-yr OS rates were 96%, 87%, 80%, and 42%, respectively. The 1-, 2-, 5-, and 10-yr CSS rates were 97%, 89%, 82%, and 69%, respectively. RFS rates at 1, 2, and 5 yr were 69%, 55%, and 45%, respectively. IV-RFS rates at 1, 2, and 5 yr were 80%, 65%, and 64%, respectively. PFS rates at 2 and 5 yr were 75% and 69%, respectively. In low-grade UTUC, OS rates at 2 and 5 yr were 93% and 77%, respectively. The 2- and 5-yr CSS rates were 98% and 88%, respectively. At 2 yr, RFS, IV-RFS, and PFS were 52%, 54%, and 94%, respectively. For high-grade UTUC, only three studies reported data on 2-yr RFS, which was 34%. The main limitation is the heterogeneity found across the studies. CONCLUSIONS AND CLINICAL IMPLICATIONS Local recurrence, bladder recurrence, and progression of UTUC occur mainly within 2 yr after eKSS. After 5-yr follow-up, OS and CSS drop, while the risk of local recurrence is non-negligible.
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Affiliation(s)
- Andrea Gallioli
- Department of Urology, Fundació Puigvert, Barcelona, Spain; Department of Surgery, Autonomous University of Barcelona, Barcelona, Spain.
| | | | - Paolo Verri
- Department of Urology, Fundació Puigvert, Barcelona, Spain
| | - Alessandro Tedde
- Department of Urology, Fundació Puigvert, Barcelona, Spain; Department of Medicine, Surgery and Pharmacy, Università degli Studi di Sassari, Sassari, Italy
| | - Laura S Mertens
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marco Moschini
- Department of Urology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Francesco Del Giudice
- Department of Maternal Infant and Urologic Sciences, "Sapienza" University of Rome, Policlinico Umberto I Hospital, Rome, Italy
| | - Francesco Soria
- Surgical Sciences, University of Turin and Città della Salute e della Scienza, Turin, Italy
| | - Ekaterina Laukhtina
- Department of Urology, Comprehensive Cancer Center and Medical University of Vienna, Vienna, Austria
| | - José Daniel Subiela
- Department of Urology, Hospital Universitario Ramón y Cajal IRYCIS Universidad de Alcalá, Madrid, Spain
| | - Wojciech Krajewski
- Minimally Invasive and Robotic Urology, Wroclaw Medical University, Wroclaw, Poland
| | - David D'Andrea
- Department of Urology, Comprehensive Cancer Center and Medical University of Vienna, Vienna, Austria
| | - Andrea Mari
- Urological Robotic Surgery and Renal Transplantation, University of Florence and Careggi Hospital, Florence, Italy
| | - Gautier Marcq
- Department of Urology, Claude Huriez Hospital, Lille, France
| | - Keiichiro Mori
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Jeremy Teoh
- Surgery, S.H. Ho Urology Centre and The Chinese University of Hong Kong, Hong Kong, China
| | - Luca Afferi
- Department of Urology, Fundació Puigvert, Barcelona, Spain; Department of Urology, Luzerner Kantonsspital, Luzern, Switzerland
| | - Simone Albisinni
- Unit of Urology, Department of Surgical Sciences, Tor Vergata University, Rome, Italy
| | | | - Joan Palou
- Department of Urology, Fundació Puigvert, Barcelona, Spain; Department of Surgery, Autonomous University of Barcelona, Barcelona, Spain
| | - Alberto Breda
- Department of Urology, Fundació Puigvert, Barcelona, Spain; Department of Surgery, Autonomous University of Barcelona, Barcelona, Spain
| | - Benjamin Pradere
- Department of Urology, Urosud La Croix du Sud Hospital, Quint Fonsegrives, France
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Head DJ, Raman JD. Kidney-Sparing Surgery for Upper Tract Urothelial Carcinoma-Modalities, Outcomes, and Limitations. J Clin Med 2024; 13:6593. [PMID: 39518735 PMCID: PMC11546368 DOI: 10.3390/jcm13216593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/23/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of urothelial cancers and is associated with high morbidity and mortality. Increasing incidence of UTUC has been observed since the 1970's, alongside the evolution of advance imaging techniques, precision biopsy equipment, and risk stratification models. The high morbidity of radical nephroureterectomy (RNU) which is still the gold-standard treatment for high-risk UTUC, has driven the development of kidney-sparing surgery alternatives for low-risk UTUC. Now, several treatment approaches have outcomes comparable to RNU for low-risk UTUC and guidelines are recommending kidney-sparing surgery for favorable low-risk disease. The main categories of kidney-sparing surgery include segmental ureterectomy, endoscopic ablation, chemoablation, and vascular-targeted phototherapy. These treatments are highly nuanced making them difficult to compare, but for most cases of favorable low-grade disease, we recommend endoscopic laser ablation with optional adjuvant intracavitary therapy. Adverse events associated with kidney-sparing surgery include ureteral stricture, bleeding requiring transfusion, and bladder recurrence of UTUC. Limitations of kidney-sparing surgery include appropriate tissue sampling (contributing to under-grading and under-staging), higher rates of ipsilateral recurrence, and potential for grade and stage progression. Collectively, these may subsequently necessitate RNU. Here, we review the technical variations and evidence behind kidney-sparing therapies as well as their practicality in the real world.
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Affiliation(s)
| | - Jay D. Raman
- Department of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA
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Roumiguié M, Seisen T, Masson-Lecomte A, Prost D, Allory Y, Xylinas E, Leon P, Bajeot AS, Pradère B, Marcq G, Neuzillet Y, Thibault C, Audenet F, Rouprêt M. French AFU Cancer Committee Guidelines - Update 2024-2026: Upper urinary tract urothelial cancer (UTUC). THE FRENCH JOURNAL OF UROLOGY 2024; 34:102722. [PMID: 39581669 DOI: 10.1016/j.fjurol.2024.102722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 08/27/2024] [Indexed: 11/26/2024]
Abstract
INTRODUCTION The purpose of this study was to propose an update of the French guidelines from the national committee ccAFU on upper tract urothelial carcinomas (UTUC). METHODS A systematic Medline search for epidemiology, risk factors, diagnosis, prognosis, treatment options and follow-up of UTUC was performed between 2022 and 2024 to evaluate available references and their levels of evidence. RESULTS UTUC is a rare malignancy with specific risk factors, including exposure to aristolochic acid and Lynch syndrome. Its diagnosis is based on the use of computed tomography urography and ureterorenoscopy with biopsies. A prognostic classification has been proposed to discriminate low- and high-risk lesions mainly on the basis of tumour grade (low/high) and imaging aspects (non-invasive/invasive). Tumour size (<2/≥2cm), focality (uni-/multifocal), and hydronephrosis (absent/present) are more relative risk factors. The standard of care for low-risk patients is currently conservative treatment involving ureterorenoscopy laser ablation, whereas radical nephroureterectomy (RNU) is advised for those with high-risk disease. Adjuvant treatments after RNU include intravesical instillation of chemotherapy to decrease the risk of bladder recurrence and delivery of platinum-based chemotherapy in pT2-T4 and/or pN+ patients. First-line treatment for metastatic UTUC is based on the combination of enfortumab vedotin plus pembrolizumab. For unfit patients, platinum-based chemotherapy plus nivolumab followed by maintenance nivolumab or platinum-based chemotherapy followed by maintenance avelumab in those with at least stable disease can be proposed. The surveillance regimen and schedule depend on the disease stage. CONCLUSION These updated guidelines will contribute to improving the management of patients diagnosed with UTUC.
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Affiliation(s)
- Mathieu Roumiguié
- Urology Department, Toulouse University Hospital, University of Toulouse UT3, Toulouse, France.
| | - Thomas Seisen
- Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Urology, Hôpital Pitié-Salpetrière, 75013 Paris, France
| | | | - Doriane Prost
- Urology Department, Paris Saint Joseph Hospital, Sorbonne University, Paris, France
| | - Y Allory
- Department of Pathology, Institut Curie, Université Paris Saclay, Saint-Cloud, France
| | - Evanguelos Xylinas
- Urology Department, Hôpital Bichat-Claude Bernard AP-HP, Université Paris Cité, Paris, France
| | | | - Anne Sophie Bajeot
- Urology Department, Toulouse University Hospital, University of Toulouse UT3, Toulouse, France
| | - Benjamin Pradère
- UROSUD Urology Department, Clinique Croix Du Sud, 31130 Quint-Fonsegrives, France
| | - Gautier Marcq
- Urology Department, Claude Huriez Hospital, CHU Lille, University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, 59000 Lille, France
| | - Yann Neuzillet
- Urology Department, Hôpital Foch, Université Paris Saclay, Suresnes, France
| | - Constance Thibault
- Medical Oncology Department, Hôpital européen Georges-Pompidou AP-HP centre, Université Paris Cité, Paris, France
| | - François Audenet
- Department of Urology, Hôpital Européen Georges-Pompidou AP-HP Centre, Université Paris Cité, Paris, France
| | - Morgan Rouprêt
- Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Urology, Hôpital Pitié-Salpetrière, 75013 Paris, France
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Lasmanovich R, Shvero A, Kleinmann N. Upper tract urothelial carcinoma: conservative management - intraluminal adjuvant therapy, and surveillance. Curr Opin Urol 2024:00042307-990000000-00204. [PMID: 39483069 DOI: 10.1097/mou.0000000000001240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
PURPOSE OF REVIEW In recent years, intraluminal therapies have become a valid alternative for low grade upper tract urothelial carcinoma (UTUC) patients, as overall survival and cancer-specific survival rates were shown to be comparable to those achieved with radical nephroureterectomy for selected cases. Nonetheless, endoscopic treatment has its limitations. As technology progresses and the demand for endoscopic treatments increases, intraluminal chemotherapy and immunotherapy instillations within the upper tract have increasingly become the subject areas of research. RECENT FINDINGS The main intraluminal therapies and relevant instillation approaches are reviewed in this study, including recent publications and their main outcomes. The recurrence rates demonstrated in the literature strengthen the notion that patients with UTUC following current intraluminal treatments have a better prognosis than in the past. Updated relevant guidelines regarding surveillance among this population are also reviewed and summarized. SUMMARY The treatment of upper tract urothelial carcinoma is clinically challenging. Developments in recent years show promising results in this field and ongoing research with new developments is emerging. Further studies are required to better understand the contribution of intraluminal therapies to the management of this disease.
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Affiliation(s)
- Rinat Lasmanovich
- Department of Urology, Sheba Medical Center, Ramat Gan
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Asaf Shvero
- Department of Urology, Sheba Medical Center, Ramat Gan
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nir Kleinmann
- Department of Urology, Sheba Medical Center, Ramat Gan
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Wong CHM, Ko ICH, Leung DKW, Liu K, Zhao H, Alvarez-Maestro M, Pes MDPL, de la Rosette J, Teoh JYC. Impact of Pre-Operative Ureteroscopy on Bladder Recurrence Following Nephroureterectomy for UTUC. Cancers (Basel) 2024; 16:2683. [PMID: 39123411 PMCID: PMC11311632 DOI: 10.3390/cancers16152683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 08/12/2024] Open
Abstract
(1) Introduction: Diagnostic ureteroscopy (URS) is an important component in the workup of upper tract urothelial carcinoma (UTUC). Whether URS was associated with increased recurrence in the bladder was not fully concluded. The current study aimed to evaluate the implication of URS on the incidences of intravesical recurrence following radical nephroureterectomy (RNU) in non-metastatic UTUC patients without prior history of bladder cancer via multi-institutional data. (2) Patients and Methods: Data were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) registry, a prospective, multicentre database. Patients with non-metastatic UTUC treated with RNU were divided into two groups: those undergoing upfront RNU and those having diagnostic URS prior to RNU. Intravesical recurrence-free survival (IVRS) was the primary endpoint, evaluated through Kaplan-Meier analysis and multivariate Cox regression. Cases with adequate follow-up data were included. (3) Results: The analysis included 269 patients. Of these, 137 (50.9%) received upfront RNU and 132 (49.1%) received pre-RNU URS. The URS group exhibited an inferior 24-month IVRS compared to the upfront RNU group (HR = 1.705, 95% CI = 1.082-2.688; p = 0.020). Multivariate analysis confirmed URS as the only significant predictor of IVR (p = 0.019). Ureteric access sheath usage, flexible ureteroscopy, ureteric biopsy, retrograde contrast studies, and the duration of URS did not significantly affect IVRS. (4) Conclusions: Diagnostic URS prior to RNU was found to be associated with an increased risk of IVR in patients with UTUC. The risk was not significantly influenced by auxiliary procedures during URS. Physicians were advised to meticulously evaluate the necessity of diagnostic URS.
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Affiliation(s)
- Chris Ho-Ming Wong
- S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Ivan Ching-Ho Ko
- S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - David Ka-Wai Leung
- S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Kang Liu
- S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Hongda Zhao
- S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | | | - Maria del Pilar Laguna Pes
- Department of Urology, Medipol Mega University Hospital, Istanbul Medipol University, Istanbul 34083, Türkiye
| | - Jean de la Rosette
- Department of Urology, Medipol Mega University Hospital, Istanbul Medipol University, Istanbul 34083, Türkiye
| | - Jeremy Yuen-Chun Teoh
- S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Department of Urology, Medical University of Vienna, 1090 Vienna, Austria
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
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Tyrrell J, Chui W, Kealey J, Sengupta S. The Utility of Intraluminal Therapies in Upper Tract Urothelial Carcinoma: A Narrative Review. Cancers (Basel) 2024; 16:1931. [PMID: 38792009 PMCID: PMC11119595 DOI: 10.3390/cancers16101931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 05/14/2024] [Accepted: 05/17/2024] [Indexed: 05/26/2024] Open
Abstract
Nephron sparing surgery (NSS) is considered for selected cases of upper tract urothelial carcinoma (UTUC) as it maintains renal function and avoids morbidity associated with radical nephroureterectomy (RNU). The appropriate selection of patients suitable for NSS without compromising oncological outcomes can sometimes be difficult, given the limitations of diagnostic modalities. Recurrence rates for UTUC can be as high as 36 to 54% after NSS. Intraluminal adjuvant therapy can be attempted following NSS to reduce recurrence, but delivery to the upper tract is more challenging than into the bladder. Bacillus Calmette-Guerin (BCG) and chemotherapy such as Mitomycin (MMC) have been administered via nephrostomy or ureteric catheter, which requires invasive/repeated instrumentation of the upper urinary tract. Drug delivery by reflux from bladder instillation along indwelling stents has also been tried but can potentially be unreliable. Recently, a gel formulation of mitomycin has been developed for the controlled exposure of the upper urinary tract to treatment over a number of hours. Drug-eluting stents to deliver chemotherapy to the upper urinary tract have been developed but have not yet entered clinical practice. Endoluminal phototherapy utilising an intravenous photosensitising agent is another novel approach that has recently been described. Intraluminal therapies may be beneficial in decreasing recurrence rates in UTUC, but currently have some limitations in their usage.
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Affiliation(s)
- Jack Tyrrell
- Urology Department, Eastern Health, Box Hill, Victoria 3128, Australia
| | - William Chui
- Urology Department, Eastern Health, Box Hill, Victoria 3128, Australia
| | - Joshua Kealey
- Urology Department, Eastern Health, Box Hill, Victoria 3128, Australia
- Eastern Health Clinical School, Monash University, Box Hill, Victoria 3128, Australia
| | - Shomik Sengupta
- Urology Department, Eastern Health, Box Hill, Victoria 3128, Australia
- Eastern Health Clinical School, Monash University, Box Hill, Victoria 3128, Australia
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Gravestock P, Cullum D, Somani B, Veeratterapillay R. Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades. Asian J Urol 2024; 11:242-252. [PMID: 38680592 PMCID: PMC11053284 DOI: 10.1016/j.ajur.2022.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 08/13/2022] [Indexed: 11/29/2022] Open
Abstract
Objective The role of ureteroscopy in the diagnosis of upper tract urothelial carcinoma is yet to be fully determined. We aimed to provide an up to date evaluation of its role and the emerging technologies in the field. Methods A literature search of the last two decades (from 24th May, 2001 to 24th May, 2021) was carried out identifying 147 papers for potential inclusion within this narrative review. Results Diagnostic ureteroscopy is undeniably useful in its ability to visualise and biopsy indeterminate lesions, and to risk stratify malignant lesions that may be suitable for kidney sparing surgery. However, an increased risk of intravesical recurrence following nephroureterectomy when a prior diagnostic ureteroscopy has been performed, inadequate sampling at biopsy, complications from the procedure, and difficult ureteric access are all potential drawbacks. Furthermore, whilst generally an accurate diagnostic procedure, it risks missing carcinoma in-situ lesions. Despite this, evidence shows that routine use of ureteroscopy changes the management of patients in a large proportion of cases, preventing unnecessary surgery or facilitating kidney sparing surgery. The overall rate of complications is low, and improved biopsy techniques and the use of tissue biomarkers for improved staging and grading are encouraging. The risks of delays to definitive management and post-ureteroscopy intravesical recurrence do not seem to affect survival, and trials are in progress to determine whether intravesical therapy can mitigate the latter. Further promising techniques are being investigated to improve shortcomings, particularly in relation to improved diagnosis of carcinoma in situ and preoperative staging. Conclusion Ureteroscopy has a role in the diagnosis of upper tract malignancy, though whether it should be used routinely is yet to be determined.
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Affiliation(s)
- Paul Gravestock
- Urology Department, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Daniel Cullum
- Urology Department, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Bhaskar Somani
- Department of Urology, University Hospital Southampton, Southampton, UK
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10
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Ghoreifi A, Sari Motlagh R, Fuchs G. Modern Kidney-Sparing Management of Upper Tract Urothelial Carcinoma. Cancers (Basel) 2023; 15:4495. [PMID: 37760465 PMCID: PMC10526335 DOI: 10.3390/cancers15184495] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 09/01/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
PURPOSE To review the latest evidence on the modern techniques and outcomes of kidney-sparing surgeries (KSS) in patients with upper tract urothelial carcinoma (UTUC). METHODS A comprehensive literature search on the study topic was conducted before 30 April 2023 using electronic databases including PubMed, MEDLINE, and EMBASE. A narrative overview of the literature was then provided based on the extracted data and a qualitative synthesis of the findings. RESULTS KSS is recommended for low- as well as select high-risk UTUCs who are not eligible for radical treatments. Endoscopic ablation is a KSS option that is associated with similar oncological outcomes compared with radical treatments while preserving renal function in well-selected patients. The other option in this setting is distal ureterectomy, which has the advantage of providing a definitive pathological stage and grade. Data from retrospective studies support the superiority of this approach over radical treatment with similar oncological outcomes, albeit in select cases. Novel chemoablation agents have also been studied in the past few years, of which mitomycin gel has received FDA approval for use in low-risk UTUCs. CONCLUSION KSSs are acceptable approaches for patients with low- and select high-risk UTUCs, which preserve renal function without compromising the oncological outcomes.
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Affiliation(s)
- Alireza Ghoreifi
- Institute of Urology, University of Southern California, Los Angeles, CA 90089, USA;
| | | | - Gerhard Fuchs
- Institute of Urology, University of Southern California, Los Angeles, CA 90089, USA;
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11
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Yoshida T, Ohe C, Nakamoto T, Kinoshita H. Learning from the past and present to change the future: Endoscopic management of upper urinary tract urothelial carcinoma. Int J Urol 2023; 30:634-647. [PMID: 37294007 DOI: 10.1111/iju.15208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 05/09/2023] [Indexed: 06/10/2023]
Abstract
Current guidelines recommend endoscopic management (EM) for patients with low-risk upper urinary tract urothelial carcinoma, as well as those with an imperative indication. However, regardless of the tumor risk, radical nephroureterectomy is still mainly performed worldwide despite the benefits of EM, such as renal function maintenance, no hemodialysis requirement, and treatment cost reduction. This might be explained by the association of EM with a high risk of local recurrence and progression. Furthermore, the need for rigorous patient selection and close surveillance following EM may be relevant. Nevertheless, recent developments in diagnostic modalities, pathological evaluation, surgical devices and techniques, and intracavitary regimens have been reported, which may contribute to improved risk stratification and treatments with superior oncological outcomes. In this review, considering recent advances in endourology and oncology, we propose novel treatment strategies for optimal EM.
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Affiliation(s)
- Takashi Yoshida
- Department of Urology and Andrology, Kansai Medical University, Osaka, Japan
- Corporate Sponsored Research Programs for Multicellular Interactions in Cancer, Kansai Medical University, Osaka, Japan
| | - Chisato Ohe
- Corporate Sponsored Research Programs for Multicellular Interactions in Cancer, Kansai Medical University, Osaka, Japan
- Department of Pathology, Kansai Medical University, Osaka, Japan
| | - Takahiro Nakamoto
- Department of Urology and Andrology, Kansai Medical University, Osaka, Japan
- Department of Pathology, Kansai Medical University, Osaka, Japan
| | - Hidefumi Kinoshita
- Department of Urology and Andrology, Kansai Medical University, Osaka, Japan
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12
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Asero V, Scornajenghi CM, Krajewski W, Szydełko T, Malkiewicz B, Nowak Ł, Gallioli A, Basran S, Chung BI, Del Giudice F. Comment on: "Animal model assessment of a new design for a coated mitomycin-eluting biodegradable ureteral stent for intracavitary instillation as an adjuvant therapy in upper urothelial carcinoma". Minerva Urol Nephrol 2023; 75:401-403. [PMID: 37221829 DOI: 10.23736/s2724-6051.23.05354-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Affiliation(s)
- Vincenzo Asero
- Department of Maternal-Infant and Urological Sciences, Umberto I Polyclinic Hospital, Sapienza University, Rome, Italy
| | - Carlo M Scornajenghi
- Department of Maternal-Infant and Urological Sciences, Umberto I Polyclinic Hospital, Sapienza University, Rome, Italy
| | - Wojciech Krajewski
- Department of Urology and Oncological Urology, Wrocław Medical University, Wrocław, Poland
| | - Tomasz Szydełko
- Department of Urology and Oncological Urology, Wrocław Medical University, Wrocław, Poland
| | - Bartosz Malkiewicz
- Department of Urology and Oncological Urology, Wrocław Medical University, Wrocław, Poland
| | - Łukasz Nowak
- Department of Urology and Oncological Urology, Wrocław Medical University, Wrocław, Poland
| | | | - Satvir Basran
- Department of Urology, Stanford University School of Medicine, Stanford, CA, USA
| | - Benjamin I Chung
- Department of Urology, Stanford University School of Medicine, Stanford, CA, USA
| | - Francesco Del Giudice
- Department of Maternal-Infant and Urological Sciences, Umberto I Polyclinic Hospital, Sapienza University, Rome, Italy -
- Department of Urology, Stanford University School of Medicine, Stanford, CA, USA
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13
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Zhang JQ, Duan Y, Wang K, Zhang XL, Jiang KH. Metachronous urothelial carcinoma in the renal pelvis, bladder, and urethra: A case report. World J Clin Cases 2023; 11:3062-3069. [PMID: 37215428 PMCID: PMC10198092 DOI: 10.12998/wjcc.v11.i13.3062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 02/06/2023] [Accepted: 03/31/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Urothelial carcinoma (UC) is a common malignancy of the urinary system that can occur anywhere from the renal pelvis to the proximal urethra. Most UCs are in the bladder and have multifocal growth. Upper urinary tract UC (UTUC), which occurs in the renal pelvis or ureter, accounts for only 5% to 10% of UCs.
CASE SUMMARY In March 2015, a 70-year-old male who initially presented to a local hospital with a complaint of painless hematuria was diagnosed with UTUC of the right renal pelvis. The doctors administered radical nephroureterectomy and bladder cuff excision. Although the doctors recommended intravesical chemotherapy and regular follow-up, he rejected this advice. In December 2016, the patient presented at our hospital with dysuria. We identified UC in the residual bladder and administered radical cystectomy and left cutaneous ureterostomy. In November 2021, he presented again with urethral bleeding. We detected urethral UC as the cause of urethral orifice bleeding and administered radical urethrectomy. Since then, he has visited regularly for 6-mo follow-ups, and was in stable condition as of December 2022.
CONCLUSION UTUC is prone to seeding and recurrence. Adjuvant instillation therapy and intense surveillance are crucial for these patients.
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Affiliation(s)
- Jian-Qing Zhang
- Department of Urology, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou Province, China
| | - Yu Duan
- Department of Urology, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou Province, China
| | - Kun Wang
- Department of Urology, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou Province, China
| | - Xiao-Li Zhang
- Department of Biomedicine, Guizhou University, Guiyang 550025, Guizhou Province, China
| | - Ke-Hua Jiang
- Department of Urology, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou Province, China
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14
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Rose KM, Narang G, Rosen G, Labatte C, Dumitrascu CI, Campagna J, Yu A, Manley BJ, Spiess PE, Li R, Adibi M, Murray KS, Sexton WJ, Humphreys MR. Antegrade administration of mitomycin gel for upper tract urothelial carcinoma via percutaneous nephrostomy tube: a multi-institutional retrospective cohort study. BJU Int 2023; 131:471-476. [PMID: 36285629 DOI: 10.1111/bju.15925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy. PATIENTS AND METHODS Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. RESULTS Thirty-two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow-up of 13.0 months post induction. CONCLUSIONS Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.
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Affiliation(s)
- Kyle M Rose
- Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Gopal Narang
- Department of Urology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Geoffrey Rosen
- Division of Urology, Department of Surgery, University of Missouri, Columbia, MO, USA
| | - Craig Labatte
- Department of Urologic Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | | | - Justin Campagna
- Department of Urology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Alice Yu
- Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Brandon J Manley
- Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Phillippe E Spiess
- Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Roger Li
- Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Mehrad Adibi
- Department of Urologic Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Katie S Murray
- Division of Urology, Department of Surgery, University of Missouri, Columbia, MO, USA
| | - Wade J Sexton
- Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
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15
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Asimakopoulos AD, Kochergin M, Klöcker C, Gakis G. The Role of Local Agents for the Treatment of Localized Upper Tract Urothelial Carcinoma: A Review of the Current Evidence. Bladder Cancer 2023; 9:15-27. [PMID: 38994483 PMCID: PMC11181742 DOI: 10.3233/blc-220093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 01/19/2023] [Indexed: 02/05/2023]
Abstract
Kidney-sparing surgery (KSS) for upper urinary tract urothelial carcinoma (UTUC) is a promising alternative to radical nephroureterectomy, especially for low-risk cases. However, due to the established risk of ipsilateral UTUC recurrence caused by the implantation of floating neoplastic cells after endoscopic resection, adjuvant endocavitary (endoureteral) instillations have been proposed. Instillation therapy may be also used as primary treatment for UTUC. The two most studied drugs that have been evaluated in both the adjuvant and primary setting of endocavitary instillation are mitomycin C and Bacillus Calmette-Guerin. The current paper provides an overview of the endocavitary treatments for UTUC, focusing on methods of administration, novel formulations, oncologic outcomes (in terms of endocavitary recurrence and progression), as well as on complications. In particular, the role of UGN-101 as a primary chemoablative treatment of primary noninvasive, endoscopically unresectable, low-grade, UTUC has been analysed. The drug achieved a complete response rate of 58% after the induction cycle, with a durable response independently of the maintenance cycle. The cumulative experience on the role of UUT instillation therapy appears encouraging; however, no definitive conclusions can be drawn about its therapeutic benefit. Given the current state of the art, any decision to administer adjuvant endoureteral therapy for UTUC should be carefully weighed against the potential adverse events. Nevertheless, newer investigations that improve visualization during ureteroscopy, genomic characterization, novel drugs and innovative strategies of improved drug delivery are under evaluation. The landscape of KSS for the treatment of the UTUC is evolving and seems promising.
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Affiliation(s)
| | - Maxim Kochergin
- Department of Urology and Neurourology, BG Unfallkrankenhaus Berlin, Berlin, Germany
| | - Christian Klöcker
- Department of Urology and Pediatric Urology, University Hospital of Würzburg, Würzburg, Germany
| | - Georgios Gakis
- Department of Urology, University Hospital of Halle, Martin-Luther University Halle-Wittenberg, Halle, Germany
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16
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Anbarasan T, Nissar S, Turbitt J, Walls K, McLuckie S, Clark C, Bourdon JC, Tracey J, Bray S, Shamsuddin A, Alcorn J, Jain S, Hislop R, Biyani CS, Nabi G. Urinary bladder recurrences following ureteroscopic biopsies of upper tract urothelial cancers: a multi-centre observational study with genomic assessment for clonality. Scott Med J 2023; 68:4-13. [PMID: 36576735 DOI: 10.1177/00369330221134233] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIMS Urinary bladder recurrences (UBRs) after radical nephroureterectomy (RNUx) are a known challenge in patients with upper-tract urothelial cancers (UTUCs). We aim to assess factors associated with UBR and clonal-relatedness with resected UTUC. METHODS Patients who underwent RNUx for UTUC between 1998 and 2015 in five institutions were identified. Clonal relatedness between primary UTUC and subsequent UBR in a sub-cohort was assessed using next-generation sequencing. A Kaplan-Meier curve was used to assess differences in UBR between two groups (with or without ureteroscopic biopsy). RESULTS Of 267 patients with complete records, 73 (27.3%) had UBR during follow-up. The five-year UBR-free survival in all patients was 64.7%. The five-year UBR-free-survival was inferior in patients who underwent URS biopsy compared with patients who did not undergo ureteroscopic biopsy (49.9% vs 76.4%, p < 0.001). History of bladder tumour (HR, 95% CI; 2.94, 1.73-5.00, p < 0.001), ureteroscopic biopsy (HR, 95% CI; 2.21, 1.38-3.53, p = 0.001) and preoperative urine cytology ≥C3 (HR, 95% CI; 2.06, 1.24-3.40, p = 0.005) were independently associated with UBR. Patients with ureteroscopic biopsy (n = 3/5) showed identical mutational changes for common genes (TP53 and FGFR3) between primary UTUC and subsequent UBR. CONCLUSIONS Ureteroscopic biopsy of UTUC is a significant risk factor for UBR. Qualitative clonality assessment showed identical mutational signatures between primary UTUC and UBR.
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Affiliation(s)
| | - Sheikh Nissar
- Department of Urology, Pilgrim Hospital, United Lincolnshire NHS Trust, England, UK
| | - Julie Turbitt
- Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Kathryn Walls
- Tayside Centre for Genomic Analysis, University of Dundee, Ninewells Hospital, Dundee, UK
| | - Sarah McLuckie
- Academic Urology Unit, Division of Imaging Sciences and Technology, University of Dundee, Ninewells Hospital, Dundee, UK
| | - Caroline Clark
- Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, UK
| | | | - Joel Tracey
- Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Susan Bray
- Division of Cellular Medicine, University of Dundee, Ninewells Hospital, Dundee, UK.,Tayside Biorepository (TBR), Ninewells Hospital, Dundee, UK
| | - Atlaf Shamsuddin
- Department of Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Jason Alcorn
- Department of Urology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK
| | - Sunjay Jain
- Pyrah Department of Urology, Leeds Teaching hospitals, NHS Trust, Leeds, UK
| | - Robert Hislop
- Department of Pathology, Ninewells Hospital, Dundee, UK
| | | | - Ghulam Nabi
- Academic Urology Unit, Division of Imaging Sciences and Technology, University of Dundee, Ninewells Hospital, Dundee, UK
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17
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Mertens LS, Sharma V, Matin SF, Boorjian SA, Houston Thompson R, van Rhijn BW, Masson-Lecomte A. Bladder Recurrence Following Upper Tract Surgery for Urothelial Carcinoma: A Contemporary Review of Risk Factors and Management Strategies. EUR UROL SUPPL 2023; 49:60-66. [PMID: 36793750 PMCID: PMC9922921 DOI: 10.1016/j.euros.2023.01.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2023] [Indexed: 01/29/2023] Open
Abstract
Context Bladder recurrences have been reported in 22-47% of patients after surgery for upper urinary tract urothelial carcinoma (UTUC). This collaborative review focuses on risk factors for and treatment strategies to reduce bladder recurrences after upper tract surgery for UTUC. Objective To review the current evidence on risk factors and treatment strategies for intravesical recurrence (IVR) after upper tract surgery for UTUC. Evidence acquisition This collaborative review is based on a literature search of PubMed/Medline, Embase, Cochrane Library, and currently available guidelines on UTUC. Relevant papers on bladder recurrence (etiology, risk factors, and management) after upper tract surgery were selected. Special attention has been paid to (1) the genetic background of bladder recurrences, (2) bladder recurrences after ureterorenoscopy (URS) with or without a biopsy, and (3) postoperative or adjuvant intravesical instillations. The literature search was performed in September 2022. Evidence synthesis Recent evidence supports the hypothesis that bladder recurrences after upper tract surgery for UTUC are often clonally related. Clinicopathologic risk factors (patient, tumor, and treatment related) have been identified for bladder recurrences after UTUC diagnosis. Specifically, the use of diagnostic ureteroscopy before radical nephroureterectomy (RNU) is associated with an increased risk of bladder recurrences. Further, a recent retrospective study suggests that performing a biopsy during ureteroscopy may further worsen IVR (no URS: 15.0%; URS without biopsy: 18.4%; URS with biopsy: 21.9%). Meanwhile, a single postoperative instillation of intravesical chemotherapy has been shown to be associated with a reduced bladder recurrence risk after RNU compared with no instillation (hazard ratio 0.51, 95% confidence interval 0.32-0.82). Currently, there are no data on the value of a single postoperative intravesical instillation after ureteroscopy. Conclusions Although based on limited retrospective data, performing URS seems to be associated with a higher risk of bladder recurrences. Future studies are warranted to assess the influence of other surgical factors as well as the role of URS biopsy or immediate postoperative intravesical chemotherapy after URS for UTUC. Patient summary In this paper, we review recent findings on bladder recurrences after upper tract surgery for upper urinary tract urothelial carcinoma.
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Affiliation(s)
- Laura S. Mertens
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands,Corresponding author. Department of Urology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Tel. +31 20 512 2553.
| | - Vidit Sharma
- Department of Urology, Mayo Clinic, Rochester, MN, USA
| | - Surena F. Matin
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | | | - Bas W.G. van Rhijn
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands,Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany
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18
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Cytotoxicity Assessment of a New Design for a Biodegradable Ureteral Mitomycin Drug-Eluting Stent in Urothelial Carcinoma Cell Culture. Polymers (Basel) 2022; 14:polym14194081. [PMID: 36236029 PMCID: PMC9570871 DOI: 10.3390/polym14194081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/10/2022] [Accepted: 09/24/2022] [Indexed: 11/29/2022] Open
Abstract
Urothelial tumour of the upper urinary tract is a rare neoplasm, but unfortunately, it has a high recurrence rate. The reduction of these tumour recurrences could be achieved by the intracavitary instillation of adjuvant chemotherapy after nephron-sparing treatment in selected patients, but current instillation methods are ineffective. Therefore, the aim of this in vitro study is to evaluate the cytotoxic capacity of a new instillation technology through a biodegradable ureteral stent/scaffold coated with a silk fibroin matrix for the controlled release of mitomycin C as an anti-cancer drug. Through a comparative study, we assessed, in urothelial carcinoma cells in a human cancer T24 cell culture for 3 and 6 h, the cytotoxic capacity of mitomycin C by viability assay using the CCK-8 test (Cell counting Kit-8). Cell viability studies in the urothelial carcinoma cell line confirm that mitomycin C embedded in the polymeric matrix does not alter its cytotoxic properties and causes a significant decrease in cell viability at 6 h versus in the control groups. These findings have a clear biomedical application and could be of great use to decrease the recurrence rate in patients with upper tract urothelial carcinomas by increasing the dwell time of anti-cancer drugs.
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19
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Chien AL, Chua KJ, Doppalapudi SK, Ghodoussipour S. The role of endoscopic management and adjuvant topical therapy for upper tract urothelial cancer. FRONTIERS IN UROLOGY 2022; 2:916259. [PMID: 38855025 PMCID: PMC11160966 DOI: 10.3389/fruro.2022.916259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/11/2024]
Abstract
Upper tract urothelial carcinoma (UTUC) has traditionally been managed with radical nephroureterectomy, and while this approach remains the gold standard for high-risk disease, endoscopic, kidney-sparing management has increasingly been adopted for low-risk disease as it preserves kidney function without compromising oncologic outcomes. Ureteroscopy and percutaneous renal access not only provide diagnoses by tumor visualization and biopsy, but also enable treatment with electrocautery or laser ablation. Several modalities exist for laser ablative treatments including thulium:YAG, neodymium:YAG, holmium:YAG, and combinations of the preceding. Furthermore, due to high recurrence rates after endoscopic management, adjuvant intracavitary instillation of various agents such as mitomycin C and bacillus Calmette-Guerin have been used given benefits seen in non-muscle invasive urothelial bladder cancer. Other formulations also being studied include gemcitabine, anthracyclines, and immunotherapies. More recently, Jelmyto, a mitomycin reverse thermal gel, has been developed to allow for adequate drug delivery time and potency since urine flow could otherwise dilute and washout topical therapy. In this article, the authors review techniques, indications, best practices, and areas of current investigation in endoscopic management and adjuvant topical therapy for UTUC.
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Affiliation(s)
- Austin L. Chien
- Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
- Division of Urology, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
| | - Kevin J. Chua
- Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
- Division of Urology, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
| | - Sai Krishnaraya Doppalapudi
- Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
- Division of Urology, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
| | - Saum Ghodoussipour
- Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
- Division of Urology, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
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20
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Assessment of a Coated Mitomycin-Releasing Biodegradable Ureteral Stent as an Adjuvant Therapy in Upper Urothelial Carcinoma: A Comparative In Vitro Study. Polymers (Basel) 2022; 14:polym14153059. [PMID: 35956574 PMCID: PMC9370495 DOI: 10.3390/polym14153059] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/25/2022] [Accepted: 07/26/2022] [Indexed: 12/16/2022] Open
Abstract
A major limitation of the treatment of low-grade upper tract urothelial carcinoma is the difficulty of intracavitary instillation of adjuvant therapy. Therefore, the aim of this in vitro study was to develop and to assess a new design of biodegradable ureteral stent coated with a silk fibroin matrix for the controlled release of mitomycin C as a chemotherapeutic drug. For this purpose, we assessed the coating of a biodegradable ureteral stent, BraidStent®, with silk fibroin and subsequently loaded the polymeric matrix with two formulations of mitomycin to evaluate its degradation rate, the concentration of mitomycin released, and changes in the pH and the weight of the stent. Our results confirm that the silk fibroin matrix is able to coat the biodegradable stent and release mitomycin for between 6 and 12 h in the urinary environment. There was a significant delay in the degradation rate of silk fibroin and mitomycin-coated stents compared to bare biodegradable stents, from 6–7 weeks to 13–14 weeks. The present study has shown the feasibility of using mitomycin C-loaded silk fibroin for the coating of biodegradable urinary stents. The addition of mitomycin C to the coating of silk fibroin biodegradable stents could be an attractive approach for intracavitary instillation in the upper urinary tract.
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21
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Drug instillation in the management of urinary tract urothelial carcinoma. Curr Opin Urol 2022; 32:531-535. [DOI: 10.1097/mou.0000000000001021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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22
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Giudici N, Bonne F, Blarer J, Minoli M, Krentel F, Seiler R. Characteristics of upper urinary tract urothelial carcinoma in the context of bladder cancer: a narrative review. Transl Androl Urol 2021; 10:4036-4050. [PMID: 34804846 PMCID: PMC8575564 DOI: 10.21037/tau-20-1472] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 04/08/2021] [Indexed: 11/20/2022] Open
Abstract
Urothelial carcinomas (UC) arise from the urothelium that covers the proximal urethra, urinary bladder, and the upper urinary tract. In daily routine and clinical trials UC originating from different locations are often treated and investigated in the same manner. However, differences between the two locations seem to be apparent and may question in handling them as a single oncologic entity. In this review we discuss similarities and differences between bladder and upper urinary tract UC and consider their potential impact on treatment strategies. Despite similarities of UC in the bladder (BC) and the upper urinary tract (UTUC), clinicopathologic and molecular differences may question to generally assemble both as a single tumor entity. Treatment standards for UTUC are often adopted from BC. However, a specific investigation in the former may still be meaningful as shown by the example of adjuvant cisplatin based chemotherapy. In conclusion, future investigations should prioritize the understanding of the tumor biology of both BC and UTUC. This may reveal which UTUC can be treated according to treatment standards of BC and in which cases, a separate approach may be more appropriate.
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Affiliation(s)
- Nicola Giudici
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Fieke Bonne
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Jennifer Blarer
- Department of Urology, Hospital Center Biel/Bienne, Biel/Bienne, Switzerland
| | - Martina Minoli
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Friedemann Krentel
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Roland Seiler
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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23
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Mori K, Katayama S, Laukhtina E, Schuettfort VM, Pradere B, Quhal F, Sari Motlagh R, Mostafaei H, Grossmann NC, Rajwa P, Zimmermann K, Karakiewicz PI, Abufaraj M, Fajkovic H, Rouprêt M, Margulis V, Enikeev DV, Egawa S, Shariat SF. Discordance Between Clinical and Pathological Staging and Grading in Upper Tract Urothelial Carcinoma. Clin Genitourin Cancer 2021; 20:95.e1-95.e6. [PMID: 34764007 DOI: 10.1016/j.clgc.2021.10.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 10/05/2021] [Accepted: 10/07/2021] [Indexed: 01/08/2023]
Abstract
INTRODUCTION This study aimed to evaluate the concordance in tumor stage and grade between ureteroscopic (URS) biopsy and radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS Records of 1,214 UTUC patients who had undergone URS biopsy followed by RNU were included. Univariable and multivariable logistic regression analyses were performed to identify factors contributing to the pathological upstaging. RESULTS The concordance between URS biopsy-based clinical and RNU pathological staging was 34.5%. Clinical understaging occurred in 59.5% patients. Upstaging to muscle-invasive disease occurred in 240 (41.7%) of 575 patients diagnosed with ≤cT1 disease. Of those diagnosed with muscle-invasive disease on final pathology, 89.6% had been clinically diagnosed with ≤cT1 disease. In the univariable analyses, computed tomography urography (CTU)-based invasion, ureter location, hydronephrosis, high-grade cytology, high-grade biopsy, sessile architecture, age, and women sex were significantly associated with pathological upstaging (P < .05). In the multivariable analyses, CTU-based invasion and hydronephrosis remained associated with pathological upstaging (P < .05). URS biopsy-based clinical and pathological gradings were concordant in 634 (54.2%) patients. Clinical undergrading occurred in 496 (42.4%) patients. CONCLUSIONS Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred in a high proportion of UTUC patients undergoing RNU. Despite the inherent selection bias, these data underline the challenges of accurate UTUC staging and grading. In daily clinical practice, URS biopsy and CTU offer the most accurate preoperative information albeit with limited predictive value when used alone. These findings should be considered when utilizing preoperative, risk-adapted strategies.
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Affiliation(s)
- Keiichiro Mori
- Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Satoshi Katayama
- Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Ekaterina Laukhtina
- Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
| | - Victor M Schuettfort
- Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Benjamin Pradere
- Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, CHRU Tours, France; Université François Rabelais de Tours, PRES Centre Val de Loire, Tours, France
| | - Fahad Quhal
- Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Reza Sari Motlagh
- Department of Urology, Medical University of Vienna, Vienna, Austria; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hadi Mostafaei
- Department of Urology, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nico C Grossmann
- Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, University Hospital Zurich, Zurich, Switzerland
| | - Pawel Rajwa
- Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland
| | | | - Pierre I Karakiewicz
- Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada
| | - Mohammad Abufaraj
- Department of Urology, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan
| | - Harun Fajkovic
- Department of Urology, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria
| | - Morgan Rouprêt
- Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitie-Salpetriere Hospital, F-75013 PARIS, France
| | - Vitaly Margulis
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX
| | - Dmitry V Enikeev
- Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
| | - Shin Egawa
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Shahrokh F Shariat
- Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Urology, Weill Cornell Medical College, New York, NY.
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24
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Ng Chieng Hin J, Hettiarachchilage D, Gravestock P, Rai B, Somani BK, Veeratterapillay R. Role of Ureteroscopy in Treatment of Upper Tract Urothelial Carcinoma. Curr Urol Rep 2021; 22:49. [PMID: 34622345 PMCID: PMC8497313 DOI: 10.1007/s11934-021-01065-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2021] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Upper tract urothelial carcinoma (UTUC) is uncommon accounting for less than 10% of all urothelial tumours. Ureteroscopic management (URS) is the first line treatment for low-risk disease and has been increasingly utilised due to technological advances and increasing surgical experience. This review looks at patient outcomes relating to URS, emerging technologies and the role of adjuvant intracavitary therapy in the management of UTUC. RECENT FINDINGS URS has firmly established itself in the management algorithm for UTUC, and a good body of evidence supports its use for low-risk disease, wherein oncological outcomes are comparable to traditional nephroureterectomy (RNU). Larger tumours can now be managed using URS with a lower morbidity than radical surgery, though with higher associated local recurrence rate and risk of progression to RNU, and as a result, patient selection and close surveillance remains key. There is limited evidence for adjuvant intracavitary therapy (Mitomycin C or BCG) in UTUC although the development of novel polymers and biodegradable stents may improve drug delivery to the upper urinary tract. URS has a clearly defined role in low-risk UTUC, and its use in larger tumours appears to be appropriate in a selected cohort of patients. The efficacy of adjuvant intracavitary therapy is as of yet undetermined, though developments in delivery techniques are promising. Likewise further developments of laser technology are anticipated to further expand the role of URS.
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Affiliation(s)
| | | | | | - Bhavan Rai
- Department of Urology, Freeman Hospital, Newcastle, UK
| | - Bhaskar K Somani
- Department of Urology, University Hospital Southamptom, Southamptom, UK.
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25
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Agarwal PK, Sfakianos JP, Feldman A, Tagawa ST, Black PC. A 25-year perspective on advances in an understanding of the biology, evaluation, treatment and future directions/challenges of urothelial cancer. Urol Oncol 2021; 39:528-547. [PMID: 34332848 DOI: 10.1016/j.urolonc.2021.05.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 11/16/2022]
Abstract
The Urologic Oncology Journal was founded 25 years ago and we reviewed the literature since that time in the area of urothelial cancer to see the progress and pitfalls we have made over this time period. A comprehensive literature search was conducted by the authors involved who are all actively involved in research, clinical trials, and treatment for urothelial cancer and the results were summarized over the past 25 years. The field of urothelial cancer has evolved tremendously in the last 25 years with the incorporation of molecular subtyping, novel imaging, immunotherapy, and robotic surgery. However, treatments such as BCG and radical cystectomy have remained steadfast over the last 25 years. Although we have a better understanding of the biology of bladder cancer, we still have a long way from being able to cure patients with bladder cancer and eliminate morbidity from treatments. Nevertheless, considerable progress has been made since the founding of the Urologic Oncology Journal 25 years ago.
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Affiliation(s)
- Piyush K Agarwal
- Section of Urology, Department of Surgery, UChicago Medicine, Chicago, IL.
| | - John P Sfakianos
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Adam Feldman
- Department of Urology, Massachusetts General Hospital, Boston, MA
| | - Scott T Tagawa
- Division of Hematology and Oncology, Departments of Medicine and Urology, Weill Cornell Medicine, New York, NY
| | - Peter C Black
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
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26
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Rouprêt M, Audenet F, Roumiguié M, Pignot G, Masson-Lecomte A, Compérat E, Houédé N, Larré S, Brunelle S, Xylinas E, Neuzillet Y, Méjean A. [French ccAFU guidelines - update 2020-2022: upper urinary tract urothelial carcinoma]. Prog Urol 2021; 30:S52-S77. [PMID: 33349430 DOI: 10.1016/s1166-7087(20)30750-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION -The purpose was to propose an update of the French guidelines from the national committee ccAFU on upper tract urothelial carcinomas (UTUC). METHODS - A systematic Medline search was performed between 2018 and 2020, as regards diagnosis, options of treatment and follow-up of UTUC, to evaluate different references with levels of evidence. RESULTS - The diagnosis of this rare pathology is based on CT-scan acquisition during excretion and ureteroscopy with histological biopsies. Radical nephroureterectomy (RNU) remains the gold standard for surgical treatment, nevertheless a conservative endoscopic approach can be proposed for low risk lesion: unifocal tumor, possible complete resection and low grade and absence of invasion on CT-scan. Close monitoring with endoscopic follow-up (flexible ureteroscopy) in compliant patients is therefore necessary. After RNU, bladder instillation of chemotherapy is recommended to reduce risk of bladder recurrence. A systemic chemotherapy is recommended after RNU in pT2-T4 N0-3 M0 disease. CONCLUSION - These updated guidelines will contribute to increase the level of urological care for diagnosis and treatment for UTUC.
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Affiliation(s)
- M Rouprêt
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Sorbonne Université, GRC n° 5, Predictive onco-urology, AP-HP, hôpital de la Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France.
| | - F Audenet
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Service d'urologie, hôpital européen Georges-Pompidou, AP-HP, université Paris-Descartes, Paris, France
| | - M Roumiguié
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Département d'urologie, CHU Rangueil, Toulouse, France
| | - G Pignot
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Service d'urologie, Institut Paoli-Calmettes, Marseille, France
| | - A Masson-Lecomte
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Service d'urologie, hôpital Saint-Louis, université Paris-Diderot, Paris, France
| | - E Compérat
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Service d'anatomie pathologique, hôpital Tenon, HUEP, Sorbonne Université, GRC n° 5, ONCOTYPE-URO, Paris, France
| | - N Houédé
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Département d'oncologie médicale, CHU Carémeau, Nîmes, Montpellier Université, France
| | - S Larré
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Service d'urologie, CHU de Reims, Reims, France
| | - S Brunelle
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Service de radiologie, Institut Paoli-Calmettes, Marseille, France
| | - E Xylinas
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Service d'urologie de l'hôpital Bichat-Claude-Bernard, AP-HP, université Paris-Descartes, Paris, France
| | - Y Neuzillet
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Service d'urologie, hôpital Foch, université de Versailles - Saint-Quentin-en-Yvelines, Suresnes, France
| | - A Méjean
- Comité de cancérologie de l'Association française d'urologie, groupe vessie, Maison de l'urologie, 11, rue Viète, 75017 Paris, France; Sorbonne Université, GRC n° 5, Predictive onco-urology, AP-HP, hôpital de la Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France
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Sanguedolce F, Fontana M, Turco M, Territo A, Balañá Lucena J, Calderón Cortez J, Vanacore D, Meneghetti I, Gallioli A, Gaya JM, Palou Redorta J, Breda A. Endoscopic Management of Upper Urinary Tract Urothelial Carcinoma: Oncologic Outcomes and Prognostic Factors in a Contemporary Cohort. J Endourol 2021; 35:1593-1600. [PMID: 33971725 DOI: 10.1089/end.2021.0133] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Introduction: Appropriate risk stratification and complete tumor ablation are the key factors to optimize the oncologic outcomes of patients undertaking endoscopic management for upper urinary tract urothelial carcinoma (UTUC). We aimed to identify risk factors associated to tumor recurrence and progression in a contemporary cohort of patients diagnosed and treated with the latest endourologic technologies. Patients and Methods: Forty-seven patients were selected between January-2015 and March-2019 for an endoscopic management of UTUC. Last generation of digital ureteroscopes with image-enhancing technologies were used for the detection of the lesions. The retrograde approach was the most frequent access (n = 45/47). The confocal laser endomicroscopy and multiple biopsy devices were variably used according to site and tumor presentation for their characterization. Holmium and Thulium lasers were variably used, with their combination being the preferred approach in case of larger lesions. Primary endpoints included the identification of factors associated with UTUC recurrence and progression, and bladder tumor recurrence. Results: Median follow-up (FU) was 24 months (interquartile range 17-44). On multivariate analysis, bladder cancer (BC) recurrence was associated to previous contralateral UTUC (hazard ratios: 5.08 confidence interval [95% CI: 1.35-18.94], p < 0.05) and tumor size (hazard ratios: 1.07 [95% CI: 1.00-1.14], p < 0.05). UTUC recurrence was associated to incomplete clearance after primary treatment (hazard ratios: 4.99 [95% CI: 1.15-21.62], p < 0.05), while UTUC progression was significantly related to the number of UTUC recurrences (hazard ratios: 3.10 [95% CI: 1.27-7.53], p < 0.05). No significant survival differences in BC/UTUC recurrence, as well as in UTUC progression, were detected between risk groups. No Clavien-Dindo grade >2 were detected; one patient developed ureteric stricture at 7-month FU. Limitations involve retrospective nature of the study and relatively small number of patients. Conclusions: The appropriate use of latest technology may enhance the oncologic outcomes of the endoscopic management of UTUC without compromising the safety of the approach. Among the prognostic factors identified in our series, UTUC recurrence seems to be associated to disease progression.
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Affiliation(s)
- Francesco Sanguedolce
- Fundació Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain.,Dipartimento di Scienze Mediche, Universitá degli Studi di Sassari, Sassari, Italy
| | - Matteo Fontana
- Fundació Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Morena Turco
- Fundació Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Angelo Territo
- Fundació Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain
| | | | | | - Davide Vanacore
- Fundació Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Iacopo Meneghetti
- Fundació Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Andrea Gallioli
- Fundació Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain
| | | | | | - Alberto Breda
- Fundació Puigvert, Universitat Autonoma de Barcelona, Barcelona, Spain
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28
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Messing EM. Topical Instillations of Chemotherapy for Renal Pelvic Urothelial Cancer. Bladder Cancer 2020. [DOI: 10.3233/blc-200012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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29
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Raman JD. Adjuvant and ablative therapies for low-risk UTUC: avenues to enhance kidney preservation. Nat Rev Urol 2020; 17:433-434. [DOI: 10.1038/s41585-020-0338-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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30
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Territo A, Gallioli A, Breda A. Response to Okeke and Rai:"Adjuvant Single-Dose Upper Urinary Tract Instillation of Mitomycin C After Therapeutic Ureteroscopy for Upper Tract Urothelial Carcinoma: A Single-Center Prospective Nonrandomized Trial" by Gallioli et al. J Endourol 2020; 34:793-794. [PMID: 32640847 DOI: 10.1089/end.2020.29095.ate] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Angelo Territo
- Fundació Puigvert, Department of Urology, Autonomous University of Barcelona, Barcelona, Spain
| | - Andrea Gallioli
- Fundació Puigvert, Department of Urology, Autonomous University of Barcelona, Barcelona, Spain.,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Clinical Sciences and Community Health, Urology, University of Milan, Milan, Italy
| | - Alberto Breda
- Fundació Puigvert, Department of Urology, Autonomous University of Barcelona, Barcelona, Spain
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31
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Subiela JD, Territo A, Mercadé A, Balañà J, Aumatell J, Calderon J, Gallioli A, González-Padilla DA, Gaya JM, Palou J, Breda A. Diagnostic accuracy of ureteroscopic biopsy in predicting stage and grade at final pathology in upper tract urothelial carcinoma: Systematic review and meta-analysis. Eur J Surg Oncol 2020; 46:1989-1997. [PMID: 32674841 DOI: 10.1016/j.ejso.2020.06.024] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/21/2020] [Accepted: 06/14/2020] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE To assess the accuracy of ureteroscopic (URS) biopsies in predicting stage and grade at final pathology in upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS The meta-analysis was performed in accordance with the PRISMA statement. Studies providing data on tumor stage and grade at URS biopsy and surgical specimens were included. The negative predictive value (NPV) implies concordance between the absence of subepithelial connective tissue invasion or the presence of low-grade tumors at URS biopsy and the absence of a muscle-invasive disease in the final pathology. RESULTS A total of 23 studies were included (3547 patients). The stage-to-stage match between URS biopsy/final pathology showed a positive predictive value (PPV) for cT1+/muscle-invasive disease of 94% (95% CI: 84%-100%) and a NPV for cTa-Tis/non-muscle-invasive disease of 60% (95% CI: 52%-68%). The grade-to-grade match between URS biopsy/final pathology was 66% (95% CI: 55%-77%) for low-grade (cLG/pLG) tumors and 97% (95% CI: 94%-98%) for high-grade (cHG/pHG) tumors. The PPV for cHG/muscle-invasive disease was 60% (95% CI: 54%-66%) and the NPV for cLG/non-muscle-invasive disease was 77% (95% CI: 73%-82%). The undergrading and understaging rates were 32% (95%CI: 25%-38%) and 46% (95% CI: 38%-54%), respectively. CONCLUSIONS There is a substantial correlation between tumor grade at URS biopsy and the final pathology. The identification of cHG tumors and subepithelial connective tissue invasion (cT1+) in URS biopsy showed a moderate and a strong correlation with invasive UTUC, respectively. Nevertheless, a certain risk of undergrading and understaging should be assumed.
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Affiliation(s)
- José Daniel Subiela
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
| | - Angelo Territo
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
| | - Asier Mercadé
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
| | - Josep Balañà
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
| | - Julia Aumatell
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
| | - Julio Calderon
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
| | - Andrea Gallioli
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Urology, Department of Clinical Sciences and Community Health, University of Milan, Via della Commenda, 10, 20122, Milan, Italy.
| | | | - Josep Maria Gaya
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
| | - Joan Palou
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
| | - Alberto Breda
- Oncology Urology Unit, Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena 340-350, 08025, Barcelona, Spain.
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32
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Okeke Z, Rai A. Editorial Comment on: "Adjuvant Single-Dose Upper Urinary Tract Instillation of Mitomycin C After Therapeutic Ureteroscopy for Upper Tract Urothelial Carcinoma: A Single-Centre Prospective Non-Randomized Trial" by Gallioli et al. J Endourol 2020; 34:791-793. [PMID: 32292039 DOI: 10.1089/end.2020.0293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Zeph Okeke
- Smith Institute for Urology, Zucker School of Medicine at Hofstra/Northwell, Lake Success, New York, USA
| | - Arun Rai
- Smith Institute for Urology, Zucker School of Medicine at Hofstra/Northwell, Lake Success, New York, USA
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