The Relationship Between A History of Bladder Cancer and The Risk of Urethral Tumors : A Systematic Review
Keywords:
Bladder cancer, urethral recurrence, radical cystectomy, orthotopic neobladder, prostatic urethral involvement, systematic reviewAbstract
Background: Bladder cancer survivors face a lifelong risk of secondary urothelial tumors due to field cancerization. Urethral recurrence (UR) after radical cystectomy (RC) is a serious but variable event. This systematic review synthesizes evidence on the relationship between a history of bladder cancer and the subsequent risk of urethral tumors.
Methods: We systematically screened RCT, etc (up to 2026) that involved human participants with documented bladder cancer, reported urethral tumor outcomes, and provided temporal data. Data extraction focused on study design, bladder cancer characteristics, urethral tumor incidence, risk estimates, and confounders.
Results: Pooled UR incidence after RC ranged from 1% to 14%, most commonly 4–5% (1–3). Orthotopic neobladder (ONB) diversion significantly reduced UR risk (OR ~0.44; 95% CI 0.24–0.79) across three independent meta-analyses (1,4,5). Prostatic urethral involvement was the strongest predictor (HR 5.35–7.95) (2,4,12). Positive urethral margins conferred the highest individual risk (HR 18.33) (12). Male sex (OR 3.16) and tumor multifocality (HR 2.97) were also significant (4). Concomitant CIS showed inconsistent significance. Asymptomatic detection of UR reduced mortality by 30% (HR 0.69) (8). Simultaneous TURBT+TURP did not increase prostatic urethral recurrence (OR 1.06) (71).
Discussion: A history of bladder cancer confers a well-defined urethral recurrence risk, strongly modified by diversion type and prostatic involvement. ONB provides a protective mechanical washout effect. Prostatic stromal invasion carries worse prognosis than mucosal involvement. Surveillance-detected UR has better survival. Simultaneous endoscopic surgery appears oncologically safe.
Conclusion: Bladder cancer history is a significant risk factor for urethral tumors. Risk-stratified surveillance (urethral wash cytology, urethroscopy in high-risk patients) and orthotopic diversion where feasible are recommended. Prophylactic urethrectomy should be reserved for very high-risk cases.
References
Fahmy O, Khairul‐Asri M, Schubert T, et al (2017) Urethral recurrence after radical cystectomy for urothelial carcinoma: A systematic review and meta-analysis. Urologic oncology. https://doi.org/10.1016/j.urolonc.2017.11.007
Li X, Wang W, Zhu G, et al (2017) Risk factors, follow-up, and treatment of urethral recurrence following radical cystectomy and urinary diversion for bladder cancer: a meta-analysis of 9498 patients. OncoTarget. https://doi.org/10.18632/oncotarget.23451
Carando R, Shariat S, Moschini M, D’andrea D (2020) Ureteral and urethral recurrence after radical cystectomy: a systematic review. Current Opinion in Urology. https://doi.org/10.1097/MOU.0000000000000752
Laukhtina E, Mori K, Andrea DD, et al (2021) Incidence, risk factors and outcomes of urethral recurrence after radical cystectomy for bladder cancer: A systematic review and meta-analysis. Urologic oncology. https://doi.org/10.1016/j.urolonc.2021.06.009
Fan B, Zhang L, Cui H, et al (2025) Development of a machine learning-based model to predict urethral recurrence following radical cystectomy: a multicentre retrospective study and updated meta-analysis. Scientific Reports. https://doi.org/10.1038/s41598-025-04893-6
Chan Y, Fisher P, Tilki D, Evans CP (2016) Urethral recurrence after cystectomy: current preventative measures, diagnosis and management. BJU International. https://doi.org/10.1111/bju.13370
Kanaroglou A, Shayegan B (2013) Management of the urethra in urothelial bladder cancer. Canadian Urological Association journal = Journal de l'Association des urologues du Canada. https://doi.org/10.5489/CUAJ.1198
Gakis G, Black P, Bochner B, et al (2017) Systematic Review on the Fate of the Remnant Urothelium after Radical Cystectomy. European Urology. https://doi.org/10.1016/j.eururo.2016.09.035
Laukhtina E, Moschini M, Soria F, et al (2022) Follow-up of the Urethra and Management of Urethral Recurrence After Radical Cystectomy: A Systematic Review and Proposal of Management Algorithm by the European Association of Urology-Young Academic Urologists: Urothelial Carcinoma Working Group. European Urology Focus. https://doi.org/10.1016/j.euf.2022.03.004
Elawdy MM, Osman Y, Taha D, El-Halwagy S (2018) Muscle-invasive bladder and urethral cancer recurrence after surgical management of upper tract urothelial carcinoma: A review of 305 patients. Turkish journal of urology. https://doi.org/10.5152/tud.2018.19677
Perlis N, Turker P, Bostrom P, et al (2013) Upper urinary tract and urethral recurrences following radical cystectomy: review of risk factors and outcomes between centres with different follow-up protocols. World journal of urology. https://doi.org/10.1007/s00345-012-0905-2
Cho K, Seo JW, Park SJ, et al (2009) The Risk Factor for Urethral Recurrence after Radical Cystectomy in Patients with Transitional Cell Carcinoma of the Bladder. Urologia internationalis. https://doi.org/10.1159/000209363
Roth B, Furrer M, Giannakis I, et al (2019) Positive Pre-cystectomy Biopsies of the Prostatic Urethra or Bladder Neck Do Not Necessarily Preclude Orthotopic Bladder Substitution. Journal of Urology. https://doi.org/10.1097/JU.0000000000000034
Huguet J, Palou J, Serrallach M, et al (2003) Management of urethral recurrence in patients with Studer ileal neobladder. European Urology. https://doi.org/10.1016/S0302-2838(03)00096-4
Dellabella M, Branchi A, Gasparri L, et al (2018) Oncological safety and quality of life in men undergoing simultaneous transurethral resection of bladder tumor and prostate: results from a randomized controlled trial. World journal of urology. https://doi.org/10.1007/s00345-018-2317-4
Stenzl A, Höltl L (2003) Orthotopic bladder reconstruction in women--what we have learned over the last decade. Critical reviews in oncology/hematology. https://doi.org/10.1016/S1040-8428(03)00078-7
Sionov B, Tsivian M, Bakaleyschik P, et al (2022) Oncological safety of simultaneous transurethral resection of high-grade urothelial carcinoma of the bladder and benign prostatic hyperplasia. Arab Journal of Urology. https://doi.org/10.1080/2090598X.2022.2142365
Zhang L, Su Q, Gao S, et al (2020) Prophylactic Urethrectomy Could Further Shorten the Female Bladder Cancer Recurrence and Metastasis. Journal of Surgical Oncology. https://doi.org/10.31487/j.jso.2020.04.07
Stein J, Penson D, Wu SD, Skinner D (2007) Pathological guidelines for orthotopic urinary diversion in women with bladder cancer: a review of the literature. Journal of Urology. https://doi.org/10.1016/J.JURO.2007.05.013
Elawdy MM, Osman Y, Taha D, et al (2017) Risk factors and prognosis of intravesical recurrence after surgical management of upper tract urothelial carcinoma: A 30-year single centre experience. Arab Journal of Urology. https://doi.org/10.1016/j.aju.2017.03.006
White S, Malkowicz S (2010) Management of the male urethra after cystectomy. Urologic clinics of North America. https://doi.org/10.1016/j.ucl.2010.04.008
Новиков АИ, Леоненков РВ, Темкин ДБ, et al (2021) Трансуретральная резекция карциномы мочевого пузыря, распространяющейся на устье мочеточника. Onkourologiâ. https://doi.org/10.17650/1726-9776-2021-17-2-104-111
Bree K, Hensley P, Brooks N, et al (2020) Impact of UTUC on Outcomes of Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacillus Calmette-Guerin. Urologic Oncology-seminars and Original Investigations. https://doi.org/10.1016/j.urolonc.2020.10.028
Huguet J (2012) Transitional cell carcinoma of the upper urinary tract after cystectomy. Archivos españoles de urología
Tsivian A, Shtricker A, Sidi A (2003) Simultaneous transurethral resection of bladder tumor and benign prostatic hyperplasia: hazardous or a safe timesaver? Journal of Urology. https://doi.org/10.1097/01.JU.0000096273.64448.E7
Novikov A, Leonenkov R, Temkin D, et al (2021) Transurethral resection of bladder cancer involving the orifice of the ureter. Cancer Urology. https://doi.org/10.17650/1726-9776-2021-17-2-104-111
Özbek M, Özen M, Öner S, et al (2021) The Factors Affecting Recurrence and Prognosis in Patients with Low-grade Stage Ta Bladder Cancer. https://doi.org/10.4274/UOB.GALENOS.2020.1558
Brookman-May S (2019) Editorial Comment. Journal of Urology. https://doi.org/10.1097/01.ju.0000550122.69979.70
Parizi MK, Margulis V, Lotan Y, et al (2022) A Systematic Review and Meta-Analysis of Clinicopathologic Factors Predicting Upper Urinary Tract Recurrence After Radical Cystectomy for Urothelial Bladder Cancer. Clinical Genitourinary Cancer. https://doi.org/10.1016/j.clgc.2022.11.002
Volkmer B, Seidl-Schlick EM, Bach D, et al (2005) Cyclophosphamide is contraindicated in patients with a history of transitional cell carcinoma. Clinical Rheumatology. https://doi.org/10.1007/s10067-004-1032-2
Seisen T, Granger B, Colin P, et al (2015) MP2-07 A SYSTEMATIC REVIEW AND META-ANALYSIS OF CLINICOPATHOLOGIC FACTORS LINKED WITH INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY TO TREAT UPPER TRACT UROTHELIAL CARCINOMA. https://doi.org/10.1016/j.juro.2015.02.130
Chang SS (2005) Short- and long-term issues regarding urethral management in male radical-cystectomy patients. Current Opinion in Urology. https://doi.org/10.1097/01.mou.0000170239.02648.6b
Ito A, Shintaku I, Satoh M, et al (2013) Intravesical seeding of upper urinary tract urothelial carcinoma cells during nephroureterectomy: an exploratory analysis from the THPMG trial. Japanese Journal of Clinical Oncology. https://doi.org/10.1093/jjco/hyt129
Wang X, Zeng M, Ju X, et al (2023) Correlation between second and first primary cancer: systematic review and meta-analysis of 9 million cancer patients. British Journal of Surgery. https://doi.org/10.1093/bjs/znad377
Cagiannos I, Morash C (2013) Surveillance strategies after definitive therapy of invasive bladder cancer. Canadian Urological Association journal = Journal de l'Association des urologues du Canada. https://doi.org/10.5489/CUAJ.1205
Huguet J (2012) [Prostatic involvement by urothelial carcinoma in patients with bladder cancer and their implications in the clinical practice]. Actas Urológicas Españolas. https://doi.org/10.1016/J.ACUROE.2012.02.004
Walsh DL, Chang SS (2009) Dilemmas in the treatment of urothelial cancers of the prostate. Urologic oncology. https://doi.org/10.1016/j.urolonc.2007.12.010
Ismail S, Karsenty G, Chartier-Kastler E, et al (2018) Prevalence, management, and prognosis of bladder cancer in patients with neurogenic bladder: A systematic review. Neurourology and Urodynamics. https://doi.org/10.1002/nau.23457
Picozzi S, Casellato S, Bozzini G, et al (2013) Inverted papilloma of the bladder: a review and an analysis of the recent literature of 365 patients. Urologic oncology. https://doi.org/10.1016/j.urolonc.2012.03.009
Lerner S, Colen J, Shen S (2008) Prostatic biology, histologic patterns and clinical consequences of transitional cell carcinoma. Current Opinion in Urology. https://doi.org/10.1097/MOU.0b013e32830b86f9
Ayyathurai R, Gómez P, Luongo T, et al (2007) Prostatic involvement by urothelial carcinoma of the bladder: clinicopathological features and outcome after radical cystectomy. BJU International. https://doi.org/10.1111/j.1464-410X.2007.07171.x
Liu JJ, Vivo ID, Wu C-Y, Giovannucci E (2021) Subsequent primary urogenital cancers among childhood and adolescent cancer survivors in the United States. Urologic oncology. https://doi.org/10.1016/j.urolonc.2021.10.009
Kotb A, Hashad MM, Elabbady A (2012) CIS of the bladder: a review of literature. https://doi.org/10.5152/TUD.2012.046
Colin P, Neuzillet Y, Pignot G, et al (2015) [Follow-up of urothelial carcinoma: Review of the Cancer Committee of the French Association of Urology]. Progrès en urologie (Paris). https://doi.org/10.1016/j.purol.2015.05.012
North A, Lakshmanan Y (2007) Malignancy associated with the use of intestinal segments in the urinary tract. Urologic oncology. https://doi.org/10.1016/J.UROLONC.2006.09.008
Ingimarsson J, Seigne J (2013) The conundrum of prostatic urethral involvement. Urologic clinics of North America. https://doi.org/10.1016/j.ucl.2013.01.010
Otto W, Denzinger S, Fritsche H, et al (2011) The WHO classification of 1973 is more suitable than the WHO classification of 2004 for predicting survival in pT1 urothelial bladder cancer. BJU International. https://doi.org/10.1111/j.1464-410X.2010.09515.x
Faba ÓR, Palou J (2012) Predictive factors for recurrence progression and cancer specific survival in high-risk bladder cancer. Current Opinion in Urology. https://doi.org/10.1097/MOU.0b013e328356ac20
Veccia A, Antonelli A, Checcucci E, et al (2019) Segmental Ureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-analysis of Comparative Studies. Clinical Genitourinary Cancer. https://doi.org/10.1016/j.clgc.2019.10.015
Autorino R, Lorenzo GD, Damiano R, et al (2009) Pathology of the prostate in radical cystectomy specimens: a critical review. Surgical oncology. https://doi.org/10.1016/j.suronc.2008.07.006
Dalibor G (2005) Review: treatment and basic epidemiological consideration on patients treated for bladder and collecting system carcinoma over last 10 years at our department
Sountoulides P, Pyrgidis N, Brookman-May S, et al (2020) Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinoma in Patients with Bladder Tumors? A Systematic Review and Meta-analysis. Journal of Urology. https://doi.org/10.1097/JU.0000000000001548
Motlagh RS, Mori K, Miura N, et al (2020) The recurrence and progression risk after simultaneous endoscopic surgery of urothelial bladder tumour and benign prostatic hyperplasia: a systematic review and meta‐analysis. BJU International. https://doi.org/10.1111/bju.15146
Cox JM, Colli J (2011) Urothelial cancers after renal transplantation. International Urology and Nephrology. https://doi.org/10.1007/s11255-011-9907-z
Zhang A, Shang D, Zhang J, et al (2015) A retrospective review of patients with urothelial cancer in 3,370 recipients after renal transplantation: a single-center experience. World journal of urology. https://doi.org/10.1007/s00345-014-1412-4
Kouriefs C, Loizides S, Mufti G (2008) Simultaneous Transurethral Resection of Bladder Tumour and Prostate: Is It Safe? Urologia internationalis. https://doi.org/10.1159/000144048
Yuan H, Chen X, Liu L, et al (2014) Risk factors for intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a meta-analysis. Urologic oncology. https://doi.org/10.1016/j.urolonc.2014.01.022
Zhou L, Liang X, Zhang K (2020) Assessment of the clinical efficacy of simultaneous transurethral resection of both bladder cancer and the prostate: a systematic review and meta-analysis. The Aging Male. https://doi.org/10.1080/13685538.2020.1718637
Tillou X, Doerfler A (2014) Urological tumors in renal transplantation. Minerva urologica e nefrologica = The Italian journal of urology and nephrology
Hu X, Xue Y, Zhu G (2023) Clinical Characteristics and Current Status of Treatment for Recurrent Bladder Cancer after Surgeries on Upper Tract Urothelial Carcinoma. Diagnostics. https://doi.org/10.3390/diagnostics13051004
Huguet J, Crego M, Sabatè S, et al (2005) Cystectomy in patients with high risk superficial bladder tumors who fail intravesical BCG therapy: pre-cystectomy prostate involvement as a prognostic factor. European Urology. https://doi.org/10.1016/J.EURURO.2005.03.021
Ugurlu O, Gonulalan U, Adsan O, et al (2007) Effects of simultaneous transurethral resection of prostate and solitary bladder tumors smaller than 3 cm on oncologic results. Urology. https://doi.org/10.1016/J.UROLOGY.2007.03.015
Hess M, Zhan E, Foo D, Yalla S (2003) Bladder Cancer In Patients With Spinal Cord Injury. Journal of Spinal Cord Medicine (JSCM). https://doi.org/10.1080/10790268.2003.11753702
Shen S, Lerner S (2007) Prostatic transitional cell carcinoma: pathologic features and clinical management. Expert Review of Anticancer Therapy. https://doi.org/10.1586/14737140.7.8.1155
Picozzi S, Ricci C, Gaeta M, et al (2012) Upper urinary tract recurrence following radical cystectomy for bladder cancer: a meta-analysis on 13,185 patients. Journal of Urology. https://doi.org/10.1016/j.juro.2012.08.017
Yuan H, Han P, Wei Q (2014) PD35-08 RISK FACTORS FOR INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA: A META-ANALYSIS. The Journal of Urology. https://doi.org/10.1016/J.JURO.2014.02.2421
Biardeau X, Chartier-Kastler E, Rouprêt M, Phé V (2016) Risk of malignancy after augmentation cystoplasty: A systematic review. Neurourology and Urodynamics. https://doi.org/10.1002/nau.22775
Monteiro LL, Witjes J, Agarwal P, et al (2018) ICUD-SIU International Consultation on Bladder Cancer 2017: management of non-muscle invasive bladder cancer. World journal of urology. https://doi.org/10.1007/s00345-018-2438-9
Lindner A, Schachtner G, Tulchiner G, et al (2021) Lynch Syndrome: Its Impact on Urothelial Carcinoma. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms22020531
Burgess K, Chow G, Edwards B, Lightner D (2011) 2190 DE NOVO DEVELOPMENT OF UROTHELIAL CARCINOMA FOLLOWING IMMUNOSUPPRESSION FOR SOLID ORGAN TRANSPLANT. The Journal of Urology. https://doi.org/10.1016/J.JURO.2011.02.2429
Savvides E, Pyrgidis N, Langas G, et al (2022) Concomitant Endoscopic Surgery for Bladder Tumors and Prostatic Obstruction: Are We Safely Hitting Two Birds with One Stone? A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. https://doi.org/10.3390/jcm11206208
Sood A, Abdollah F, Cole D, Alanee S (2018) Re: Stenting prior to Cystectomy is an Independent Risk Factor for Upper Urinary Tract Recurrence: B. Kiss, M. A. Furrer, P. Y. Wuethrich, F. C. Burkhard, G. N. Thalmann and B. Roth J Urol 2017;198:1263-1268. Journal of Urology. https://doi.org/10.1016/j.juro.2017.11.119
Clark P (2007) Upper tract transitional cell carcinoma: Finding a way forward. Cancer. https://doi.org/10.1002/cncr.22969
Johnston D, Bishop MW, Hudson M, Giel D (2015) Subsequent Neoplasms in Adult Survivors of Childhood Genitourinary Tumors. Urology. https://doi.org/10.1016/j.urology.2015.07.022
Bahadori A, Bray G, Rukin N (2023) Secondary tumours in orthotopic neobladder using isolated gut segment post radical cystectomy for urothelial carcinoma: a systematic review. International Urology and Nephrology. https://doi.org/10.1007/s11255-023-03745-4
Liedberg F, Chebil G, Davidsson T, et al (2003) Transitional cell carcinoma der Prostata im Zystoprostatektomiepräparat. Aktuelle Urologie. https://doi.org/10.1055/S-2003-42002
Shahzad M, Jamil MN, Ashraf H, Islam EU (2023) Diagnostic, Therapeutic and Prognostic Implications of Urothelial Carcinoma, A Review. Pakistan journal of health sciences. https://doi.org/10.54393/pjhs.v4i05.720
Picozzi S, Ricci C, Gaeta M, et al (2012) Is it oncologically safe performing simultaneous transurethral resection of the bladder and prostate? A meta-analysis on 1,234 patients. International Urology and Nephrology. https://doi.org/10.1007/s11255-012-0183-3
Sanghi V, Kumar MA, Alkhayyat M, et al (2020) S0432 Men With Metabolic Syndrome Are at Increased Risk of Urogenital Cancers Among Patients With Barrett's Esophagus. The American Journal of Gastroenterology. https://doi.org/10.14309/01.ajg.0000703776.13183.b0
Kajtezovic S, Walker AR, Hjalmarsson B, et al (2022) Management of secondary Paget’s disease of the vulva associated with transitional cell carcinoma. Journal of Cancer Research and Clinical Oncology. https://doi.org/10.1007/s00432-022-04007-z
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