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Non-urothelial bladder cancer

Author
David I Quinn, MBBS (Hons I), PhD, FRACP, FACP
Section Editors
Seth P Lerner, MD
Derek Raghavan, MD, PhD, FACP, FASCO
Deputy Editor
Michael E Ross, MD

INTRODUCTION

Bladder cancers are the most common genitourinary malignancy in both men and women. They are broadly categorized as urothelial and non-urothelial. (See "Pathology of bladder neoplasms".)

The clinical features and treatment of non-urothelial bladder cancers will be reviewed here. Small cell carcinoma of the bladder is discussed elsewhere, as is an overview of urothelial bladder cancer. (See "Small cell carcinoma of the bladder" and "Overview of the initial approach and management of urothelial bladder cancer".)

EPIDEMIOLOGY

Non-urothelial bladder cancer accounts for less than 5 percent of all bladder tumors [1]. Approximately 90 percent of non-urothelial bladder cancers are epithelial in origin, and these include squamous cell carcinoma, adenocarcinoma, and small cell carcinoma.

Non-epithelial tumors include sarcoma, carcinosarcoma, paraganglioma, melanoma, and lymphoma. Risk factors for non-urothelial bladder cancers are discussed below in specific sections for different tumor types. (See 'Non-epithelial bladder tumors' below.)

PATHOGENESIS AND RISK FACTORS

The pathogenesis of non-urothelial bladder cancers is incompletely understood. Both the development of metaplasia and the presence of chronic infection are believed to be important factors in tumorigenesis. Alternative hypotheses include the development of non-urothelial bladder cancers from preexisting urothelial (transitional cell) carcinomas that undergo metaplasia [2], and tumor development from multipotent stem cells in the bladder.

                         

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Literature review current through: Nov 2016. | This topic last updated: Wed Nov 23 00:00:00 GMT 2016.
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References
Top
  1. Dahm P, Gschwend JE. Malignant non-urothelial neoplasms of the urinary bladder: a review. Eur Urol 2003; 44:672.
  2. Kunze E. Histogenesis of nonurothelial carcinomas in the human and rat urinary bladder. Exp Toxicol Pathol 1998; 50:341.
  3. Ozbey I, Aksoy Y, Polat O, et al. Squamous metaplasia of the bladder: findings in 14 patients and review of the literature. Int Urol Nephrol 1999; 31:457.
  4. Khan MS, Thornhill JA, Gaffney E, et al. Keratinising squamous metaplasia of the bladder: natural history and rationalization of management based on review of 54 years experience. Eur Urol 2002; 42:469.
  5. El-Merzabani MM, El-Aaser AA, Zakhary NI. A study on the aetiological factors of bilharzial bladder cancer in Egypt--1. Nitrosamines and their precursors in urine. Eur J Cancer 1979; 15:287.
  6. Radomski JL, Greenwald D, Hearn WL, et al. Nitrosamine formation in bladder infections and its role in the etiology of bladder cancer. J Urol 1978; 120:48.
  7. Bartsch H, Montesano R. Relevance of nitrosamines to human cancer. Carcinogenesis 1984; 5:1381.
  8. Wogan GN, Hecht SS, Felton JS, et al. Environmental and chemical carcinogenesis. Semin Cancer Biol 2004; 14:473.
  9. Oliveira PA, Colaco A, De la Cruz P LF, Lopes C. Experimental bladder carcinogenesis-rodent models. Exp Oncol 2006; 28:2.
  10. El-Mosalamy H, Salman TM, Ashmawey AM, Osama N. Role of chronic E. coli infection in the process of bladder cancer- an experimental study. Infect Agent Cancer 2012; 7:19.
  11. Cohen AJ, Packiam V, Nottingham C, et al. Upstaging of nonurothelial histology in bladder cancer at the time of surgical treatment in the National Cancer Data Base. Urol Oncol 2016.
  12. Ghoneim MA, Ashamallah AK, Awaad HK, Whitmore WF Jr. Randomized trial of cystectomy with or without preoperative radiotherapy for carcinoma of the bilharzial bladder. J Urol 1985; 134:266.
  13. Awwad H, El-Baki HA, El-Bolkainy N, et al. Pre-operative irradiation of T3-carcinoma in bilharzial bladder: a comparison between hyperfractionation and conventional fractionation. Int J Radiat Oncol Biol Phys 1979; 5:787.
  14. Collazo-Lorduy A, Castillo-Martin M, Wang L, et al. Urachal Carcinoma Shares Genomic Alterations with Colorectal Carcinoma and May Respond to Epidermal Growth Factor Inhibition. Eur Urol 2016.
  15. Loh KP, Mondo E, Hansen EA, et al. Targeted Therapy Based on Tumor Genomic Analyses in Metastatic Urachal Carcinoma. Clin Genitourin Cancer 2016; 14:e449.
  16. Abrams J, Conley B, Mooney M, et al. National Cancer Institute's Precision Medicine Initiatives for the new National Clinical Trials Network. Am Soc Clin Oncol Educ Book 2014; :71.
  17. Redig AJ, Jänne PA. Basket trials and the evolution of clinical trial design in an era of genomic medicine. J Clin Oncol 2015; 33:975.
  18. Kantor AF, Hartge P, Hoover RN, Fraumeni JF Jr. Epidemiological characteristics of squamous cell carcinoma and adenocarcinoma of the bladder. Cancer Res 1988; 48:3853.
  19. Fortuny J, Kogevinas M, Chang-Claude J, et al. Tobacco, occupation and non-transitional-cell carcinoma of the bladder: an international case-control study. Int J Cancer 1999; 80:44.
  20. Subramonian K, Cartwright RA, Harnden P, Harrison SC. Bladder cancer in patients with spinal cord injuries. BJU Int 2004; 93:739.
  21. Pannek J. Transitional cell carcinoma in patients with spinal cord injury: a high risk malignancy? Urology 2002; 59:240.
  22. Hamid R, Bycroft J, Arya M, Shah PJ. Screening cystoscopy and biopsy in patients with neuropathic bladder and chronic suprapubic indwelling catheters: is it valid? J Urol 2003; 170:425.
  23. Yang CC, Clowers DE. Screening cystoscopy in chronically catheterized spinal cord injury patients. Spinal Cord 1999; 37:204.
  24. Scosyrev E, Yao J, Messing E. Urothelial carcinoma versus squamous cell carcinoma of bladder: is survival different with stage adjustment? Urology 2009; 73:822.
  25. Rundle JS, Hart AJ, McGeorge A, et al. Squamous cell carcinoma of bladder. A review of 114 patients. Br J Urol 1982; 54:522.
  26. Swanson DA, Liles A, Zagars GK. Preoperative irradiation and radical cystectomy for stages T2 and T3 squamous cell carcinoma of the bladder. J Urol 1990; 143:37.
  27. Richie JP, Waisman J, Skinner DG, Dretler SP. Squamous carcinoma of the bladder: treatment by radical cystectomy. J Urol 1976; 115:670.
  28. Tannenbaum SI, Carson CC 3rd, Tatum A, Paulson DF. Squamous carcinoma of urinary bladder. Urology 1983; 22:597.
  29. James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012; 366:1477.
  30. Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 1996; 14:2527.
  31. Ryan DP, Compton CC, Mayer RJ. Carcinoma of the anal canal. N Engl J Med 2000; 342:792.
  32. Serretta V, Pomara G, Piazza F, Gange E. Pure squamous cell carcinoma of the bladder in western countries. Report on 19 consecutive cases. Eur Urol 2000; 37:85.
  33. Galsky MD, Iasonos A, Mironov S, et al. Prospective trial of ifosfamide, paclitaxel, and cisplatin in patients with advanced non-transitional cell carcinoma of the urothelial tract. Urology 2007; 69:255.
  34. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016; 387:1909.
  35. Hussain M, Vaishampayan U, Du W, et al. Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for advanced urothelial cancer. J Clin Oncol 2001; 19:2527.
  36. Grignon DJ, Ro JY, Ayala AG, et al. Primary adenocarcinoma of the urinary bladder. A clinicopathologic analysis of 72 cases. Cancer 1991; 67:2165.
  37. Fiter L, Gimeno F, Martin L, Gómez Tejeda L. Signet-ring cell adenocarcinoma of bladder. Urology 1993; 41:30.
  38. Zaghloul MS, Nouh A, Nazmy M, et al. Long-term results of primary adenocarcinoma of the urinary bladder: a report on 192 patients. Urol Oncol 2006; 24:13.
  39. Wilson TG, Pritchett TR, Lieskovsky G, et al. Primary adenocarcinoma of bladder. Urology 1991; 38:223.
  40. Manunta A, Vincendeau S, Kiriakou G, et al. Non-transitional cell bladder carcinomas. BJU Int 2005; 95:497.
  41. Johnson DE, Hodge GB, Abdul-Karim FW, Ayala AG. Urachal carcinoma. Urology 1985; 26:218.
  42. Kakizoe T, Matsumoto K, Andoh M, et al. Adenocarcinoma of urachus. Report of 7 cases and review of literature. Urology 1983; 21:360.
  43. Sheldon CA, Clayman RV, Gonzalez R, et al. Malignant urachal lesions. J Urol 1984; 131:1.
  44. Wright JL, Porter MP, Li CI, et al. Differences in survival among patients with urachal and nonurachal adenocarcinomas of the bladder. Cancer 2006; 107:721.
  45. Dhillon J, Liang Y, Kamat AM, et al. Urachal carcinoma: a pathologic and clinical study of 46 cases. Hum Pathol 2015; 46:1808.
  46. CULP DA. THE HISTOLOGY OF THE EXSTROPHIED BLADDER. J Urol 1964; 91:538.
  47. Hughes MJ, Fisher C, Sohaib SA. Imaging features of primary nonurachal adenocarcinoma of the bladder. AJR Am J Roentgenol 2004; 183:1397.
  48. Ashley RA, Inman BA, Sebo TJ, et al. Urachal carcinoma: clinicopathologic features and long-term outcomes of an aggressive malignancy. Cancer 2006; 107:712.
  49. Niedworok C, Panitz M, Szarvas T, et al. Urachal Carcinoma of the Bladder: Impact of Clinical and Immunohistochemical Parameters on Prognosis. J Urol 2016; 195:1690.
  50. Szarvas T, Módos O, Niedworok C, et al. Clinical, prognostic, and therapeutic aspects of urachal carcinoma-A comprehensive review with meta-analysis of 1,010 cases. Urol Oncol 2016; 34:388.
  51. Xiaoxu L, Jianhong L, Jinfeng W, Klotz LH. Bladder adenocarcinoma: 31 reported cases. Can J Urol 2001; 8:1380.
  52. Thomas DG, Ward AM, Williams JL. A study of 52 cases of adenocarcinoma of the bladder. Br J Urol 1971; 43:4.
  53. Abenoza P, Manivel C, Fraley EE. Primary adenocarcinoma of urinary bladder. Clinicopathologic study of 16 cases. Urology 1987; 29:9.
  54. Anderström C, Johansson SL, von Schultz L. Primary adenocarcinoma of the urinary bladder. A clinicopathologic and prognostic study. Cancer 1983; 52:1273.
  55. Hong JY, Choi MK, Uhm JE, et al. Palliative chemotherapy for non-transitional cell carcinomas of the urothelial tract. Med Oncol 2009; 26:186.
  56. Smith DC, Mackler NJ, Dunn RL, et al. Phase II trial of paclitaxel, carboplatin and gemcitabine in patients with locally advanced carcinoma of the bladder. J Urol 2008; 180:2384.
  57. Pagliaro LC, Williams DL, Daliani D, et al. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol 2010; 28:3851.
  58. Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22:23.
  59. Yanagihara Y, Tanji N, Miura N, et al. Modified FOLFOX6 chemotherapy in patients with metastatic urachal cancer. Chemotherapy 2013; 59:402.
  60. Ghoneim MA, Abdel-Latif M, el-Mekresh M, et al. Radical cystectomy for carcinoma of the bladder: 2,720 consecutive cases 5 years later. J Urol 2008; 180:121.
  61. Mostafa MH, Sheweita SA, O'Connor PJ. Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev 1999; 12:97.
  62. el-Mawla NG, el-Bolkainy MN, Khaled HM. Bladder cancer in Africa: update. Semin Oncol 2001; 28:174.
  63. Hassan N, Mounir M, El-Basmi A, et al. Statistical Report for NCI. National Cancer Institute; Cairo, 2001.
  64. Salem S, Mitchell RE, El-Alim El-Dorey A, et al. Successful control of schistosomiasis and the changing epidemiology of bladder cancer in Egypt. BJU Int 2011; 107:206.
  65. Gouda I, Mokhtar N, Bilal D, et al. Bilharziasis and bladder cancer: a time trend analysis of 9843 patients. J Egypt Natl Canc Inst 2007; 19:158.
  66. Shokeir AA. Squamous cell carcinoma of the bladder: pathology, diagnosis and treatment. BJU Int 2004; 93:216.
  67. Zaghloul MS, Awwad HK, Akoush HH, et al. Postoperative radiotherapy of carcinoma in bilharzial bladder: improved disease free survival through improving local control. Int J Radiat Oncol Biol Phys 1992; 23:511.
  68. Gad el Mawla N, Mansour MA, Eissa S, et al. A randomized pilot study of high-dose epirubicin as neoadjuvant chemotherapy in the treatment of cancer of the bilharzial bladder. Ann Oncol 1991; 2:137.
  69. Khaled H, Zaghloul M, Ghoneim M, et al. Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive bladder cancer: Effect on bladder preservation and survival. Proc Am Soc Clin Oncol 2003; 22:411 (abstr 1652).
  70. Zaghoul MS, Khaled HM, Lotayef M, et al. A controlled prospective randomized trial of adjuvant chemoradiotherapy following radical cystectomy in advanced high risk bladder cancer (abstract). J Clin Oncol 2007; 25:255s.
  71. Khaled HM, Hamza MR, Mansour O, et al. A phase II study of gemcitabine plus cisplatin chemotherapy in advanced bilharzial bladder carcinoma. Eur J Cancer 2000; 36 Suppl 2:34.
  72. Russo P, Singer S, Maki R. Adult genitourinary soft tissue sarcoma. In: Comprehensive textbook of genitourinary oncology, 4th ed, Scardino PT, Linehan WM, Zelefsky MJ, Vogelzang NJ (Eds), Lippincott Williams & Wilkins, Baltimore 2011. Chapter 52.
  73. Parekh DJ, Jung C, O'Conner J, et al. Leiomyosarcoma in urinary bladder after cyclophosphamide therapy for retinoblastoma and review of bladder sarcomas. Urology 2002; 60:164.
  74. Russo P, Brady MS, Conlon K, et al. Adult urological sarcoma. J Urol 1992; 147:1032.
  75. Spiess PE, Kassouf W, Steinberg JR, et al. Review of the M.D. Anderson experience in the treatment of bladder sarcoma. Urol Oncol 2007; 25:38.
  76. Lopez-Beltran A, Pacelli A, Rothenberg HJ, et al. Carcinosarcoma and sarcomatoid carcinoma of the bladder: clinicopathological study of 41 cases. J Urol 1998; 159:1497.
  77. Whalen RK, Althausen AF, Daniels GH. Extra-adrenal pheochromocytoma. J Urol 1992; 147:1.
  78. Tainio HM, Kylmälä TM, Haapasalo HK. Primary malignant melanoma of the urinary bladder associated with widespread metastases. Scand J Urol Nephrol 1999; 33:406.
  79. Kempton CL, Kurtin PJ, Inwards DJ, et al. Malignant lymphoma of the bladder: evidence from 36 cases that low-grade lymphoma of the MALT-type is the most common primary bladder lymphoma. Am J Surg Pathol 1997; 21:1324.
  80. Bates AW, Norton AJ, Baithun SI. Malignant lymphoma of the urinary bladder: a clinicopathological study of 11 cases. J Clin Pathol 2000; 53:458.
  81. Al-Maghrabi J, Kamel-Reid S, Jewett M, et al. Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type arising in the urinary bladder: report of 4 cases with molecular genetic analysis. Arch Pathol Lab Med 2001; 125:332.
  82. Abrahamson JS, Michaelson MD. Malignant lymphoma of the genitourinary tract. In: Comprehensive textbook of genitourinary oncology, 4th ed, Scardino PT, Linehan WM, Zelefsky MJ, Vogelzang NJ (Eds), Lippincott Williams & Wilkins, Baltimore 2011. Chapter 53.
  83. Porcaro AB, Gilioli E, Migliorini F, et al. Primary lymphoepithelioma-like carcinoma of the urinary bladder: report of one case with review and update of the literature after a pooled analysis of 43 patients. Int Urol Nephrol 2003; 35:99.
  84. Mayer EK, Beckley I, Winkler MH. Lymphoepithelioma-like carcinoma of the urinary bladder--diagnostic and clinical implications. Nat Clin Pract Urol 2007; 4:167.
  85. Nishiyama H, Habuchi T, Watanabe J, et al. Clinical outcome of a large-scale multi-institutional retrospective study for locally advanced bladder cancer: a survey including 1131 patients treated during 1990-2000 in Japan. Eur Urol 2004; 45:176.