Skip to main content

Advertisement

Log in

Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC)

  • Topic Paper
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment.

Methods

Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance.

Results

UTUC accounts for 5–10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed.

Conclusions

Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Green DA, Rink M, Xylinas E, Matin SF, Stenzl A, Roupret M et al (2013) Urothelial carcinoma of the bladder and the upper tract: disparate twins. J Urol 189:1214–1221. doi:10.1016/j.juro.2012.05.079

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30. doi:10.3322/caac.21332

    Article  PubMed  Google Scholar 

  3. Raman JD, Messer J, Sielatycki JA, Hollenbeak CS (2011) Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA, 1973–2005. BJU Int 107:1059–1064. doi:10.1111/j.1464-410X.2010.09675.x

    Article  PubMed  Google Scholar 

  4. Shariat SF, Favaretto RL, Gupta A, Fritsche H-M, Matsumoto K, Kassouf W et al (2011) Gender differences in radical nephroureterectomy for upper tract urothelial carcinoma. World J Urol 29:481–486. doi:10.1007/s00345-010-0594-7

    Article  PubMed  Google Scholar 

  5. Shariat SF, Favaretto RL, Gupta A, Fritsche H-M, Matsumoto K, Kassouf W et al (2011) Gender differences in radical nephroureterectomy for upper tract urothelial carcinoma. World J Urol 29:481–486. doi:10.1007/s00345-010-0594-7

    Article  PubMed  Google Scholar 

  6. Matsumoto K, Novara G, Gupta A, Margulis V, Walton TJ, Roscigno M et al (2011) Racial differences in the outcome of patients with urothelial carcinoma of the upper urinary tract: an international study. BJU Int 108:E304–E309. doi:10.1111/j.1464-410X.2011.10188.x

    Article  PubMed  Google Scholar 

  7. Favaretto RL, Shariat SF, Chade DC, Godoy G, Adamy A, Kaag M et al (2010) The effect of tumor location on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center. Eur Urol 58:574–580. doi:10.1016/j.eururo.2010.07.003

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lughezzani G, Jeldres C, Isbarn H, Sun M, Shariat SF, Widmer H et al (2010) Temporal stage and grade migration in surgically treated patients with upper tract urothelial carcinoma. BJU Int 105:799–804. doi:10.1111/j.1464-410X.2009.08818.x

    Article  PubMed  Google Scholar 

  9. Cosentino M, Palou J, Gaya JM, Breda A, Rodriguez-Faba O, Villavicencio-Mavrich H (2013) Upper urinary tract urothelial cell carcinoma: location as a predictive factor for concomitant bladder carcinoma. World J Urol 31:141–145. doi:10.1007/s00345-012-0877-2

    Article  PubMed  Google Scholar 

  10. Otto W, Shariat SF, Fritsche H-M, Gupta A, Matsumoto K, Kassouf W et al (2011) Concomitant carcinoma in situ as an independent prognostic parameter for recurrence and survival in upper tract urothelial carcinoma: a multicenter analysis of 772 patients. World J Urol 29:487–494. doi:10.1007/s00345-011-0645-8

    Article  PubMed  Google Scholar 

  11. Colin P, Koenig P, Ouzzane A, Berthon N, Villers A, Biserte J et al (2009) Environmental factors involved in carcinogenesis of urothelial cell carcinomas of the upper urinary tract. BJU Int 104:1436–1440. doi:10.1111/j.1464-410X.2009.08838.x

    Article  CAS  PubMed  Google Scholar 

  12. McLaughlin JK, Silverman DT, Hsing AW, Ross RK, Schoenberg JB, Yu MC et al (1992) Cigarette smoking and cancers of the renal pelvis and ureter. Cancer Res 52:254–257

    CAS  PubMed  Google Scholar 

  13. Rink M, Xylinas E, Margulis V, Cha EK, Ehdaie B, Raman JD et al (2013) Impact of smoking on oncologic outcomes of upper tract urothelial carcinoma after radical nephroureterectomy. Eur Urol 63:1082–1090. doi:10.1016/j.eururo.2012.06.029

    Article  PubMed  Google Scholar 

  14. Rink M, Xylinas E, Trinh Q-D, Lotan Y, Margulis V, Raman JD et al (2013) Gender-specific effect of smoking on upper tract urothelial carcinoma outcomes. BJU Int 112:623–637. doi:10.1111/bju.12014

    Article  PubMed  Google Scholar 

  15. Shinka T, Miyai M, Sawada Y, Inagaki T, Okawa T (1995) Factors affecting the occurrence of urothelial tumors in dye workers exposed to aromatic amines. Int J Urol 2:243–248

    Article  CAS  PubMed  Google Scholar 

  16. De Broe ME, Elseviers MM (1998) Analgesic nephropathy. N Engl J Med 338:446–452. doi:10.1056/NEJM199802123380707

    Article  PubMed  Google Scholar 

  17. Chen C-H, Dickman KG, Moriya M, Zavadil J, Sidorenko VS, Edwards KL et al (2012) Aristolochic acid-associated urothelial cancer in Taiwan. Proc Natl Acad Sci USA 109:8241–8246. doi:10.1073/pnas.1119920109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rouprêt M, Yates DR, Comperat E, Cussenot O (2008) Upper urinary tract urothelial cell carcinomas and other urological malignancies involved in the hereditary nonpolyposis colorectal cancer (lynch syndrome) tumor spectrum. Eur Urol 54:1226–1236. doi:10.1016/j.eururo.2008.08.008

    Article  PubMed  Google Scholar 

  19. Koornstra JJ, Mourits MJ, Sijmons RH, Leliveld AM, Hollema H, Kleibeuker JH (2009) Management of extracolonic tumours in patients with Lynch syndrome. Lancet Oncol 10:400–408. doi:10.1016/S1470-2045(09)70041-5

    Article  CAS  PubMed  Google Scholar 

  20. Rouprêt M, Babjuk M, Compérat E, Zigeuner R, Sylvester RJ, Burger M et al (2015) European association of urology guidelines on upper urinary tract urothelial cell carcinoma: 2015 update. Eur Urol 68:868–879. doi:10.1016/j.eururo.2015.06.044

    Article  PubMed  Google Scholar 

  21. Rouprêt M, Drouin SJ, Cancel-Tassin G, Comperat E, Larré S, Cussenot O (2012) Genetic variability in 8q24 confers susceptibility to urothelial carcinoma of the upper urinary tract and is linked with patterns of disease aggressiveness at diagnosis. J Urol 187:424–428. doi:10.1016/j.juro.2011.10.038

    Article  PubMed  Google Scholar 

  22. Sasaki M, Sakano S, Okayama N, Akao J, Hara T, Kawai Y et al (2008) DNA repair gene polymorphisms may be associated with prognosis of upper urinary tract transitional cell carcinoma. Neoplasia 10:255–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Raman JD, Shariat SF, Karakiewicz PI, Lotan Y, Sagalowsky AI, Roscigno M et al (2011) Does preoperative symptom classification impact prognosis in patients with clinically localized upper-tract urothelial carcinoma managed by radical nephroureterectomy? Urol Oncol 29:716–723. doi:10.1016/j.urolonc.2009.11.007

    Article  PubMed  Google Scholar 

  24. Inman BA, Tran V-T, Fradet Y, Lacombe L (2009) Carcinoma of the upper urinary tract: predictors of survival and competing causes of mortality. Cancer 115:2853–2862. doi:10.1002/cncr.24339

    Article  PubMed  Google Scholar 

  25. Renshaw AA (2006) Comparison of ureteral washing and biopsy specimens in the community setting. Cancer 108:45–48. doi:10.1002/cncr.21456

    Article  PubMed  Google Scholar 

  26. Williams SK, Denton KJ, Minervini A, Oxley J, Khastigir J, Timoney AG et al (2008) Correlation of upper-tract cytology, retrograde pyelography, ureteroscopic appearance, and ureteroscopic biopsy with histologic examination of upper-tract transitional cell carcinoma. J Endourol 22:71–76. doi:10.1089/end.2007.9853

    Article  PubMed  Google Scholar 

  27. Messer J, Shariat SF, Brien JC, Herman MP, Ng CK, Scherr DS et al (2011) Urinary cytology has a poor performance for predicting invasive or high-grade upper-tract urothelial carcinoma. BJU Int 108:701–705. doi:10.1111/j.1464-410X.2010.09899.x

    PubMed  Google Scholar 

  28. Reynolds JP, Voss JS, Kipp BR, Karnes RJ, Nassar A, Clayton AC et al (2014) Comparison of urine cytology and fluorescence in situ hybridization in upper urothelial tract samples. Cancer Cytopathol 122:459–467. doi:10.1002/cncy.21414

    Article  PubMed  Google Scholar 

  29. Fernández MI, Parikh S, Grossman HB, Katz R, Matin SF, Dinney CPN et al (2012) The role of FISH and cytology in upper urinary tract surveillance after radical cystectomy for bladder cancer. Urol Oncol 30(6):821–824. doi:10.1016/j.urolonc.2010.08.006

    Article  PubMed  Google Scholar 

  30. Chlapoutakis K, Theocharopoulos N, Yarmenitis S, Damilakis J (2010) Performance of computed tomographic urography in diagnosis of upper urinary tract urothelial carcinoma, in patients presenting with hematuria: systematic review and meta-analysis. Eur J Radiol 73:334–338. doi:10.1016/j.ejrad.2008.10.026

    Article  PubMed  Google Scholar 

  31. Fritz GA, Schoellnast H, Deutschmann HA, Quehenberger F, Tillich M (2006) Multiphasic multidetector-row CT (MDCT) in detection and staging of transitional cell carcinomas of the upper urinary tract. Eur Radiol 16:1244–1252. doi:10.1007/s00330-005-0078-0

    Article  PubMed  Google Scholar 

  32. Millán-Rodríguez F, Palou J, de la Torre-Holguera P, Vayreda-Martija JM, Villavicencio-Mavrich H, Vicente-Rodríguez J (1999) Conventional CT signs in staging transitional cell tumors of the upper urinary tract. Eur Urol 35:318–322. doi:19869

    Article  PubMed  Google Scholar 

  33. Takahashi N, Kawashima A, Glockner JF, Hartman RP, Leibovich BC, Brau ACS et al (2008) Small (<2-cm) upper-tract urothelial carcinoma: evaluation with gadolinium-enhanced three-dimensional spoiled gradient-recalled echo MR urography 1. Radiology 247:451–457. doi:10.1148/radiol.2472070798

    Article  PubMed  Google Scholar 

  34. Tanaka H, Yoshida S, Komai Y, Sakai Y, Urakami S, Yuasa T et al (2016) Clinical value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in upper tract urothelial carcinoma: impact on detection of metastases and patient management. Urol Int 96:65–72. doi:10.1159/000381269

    Article  CAS  PubMed  Google Scholar 

  35. Tsivian A, Tsivian M, Stanevsky Y, Tavdy E, Sidi AA (2014) Routine diagnostic ureteroscopy for suspected upper tract transitional-cell carcinoma. J Endourol 28:922–925. doi:10.1089/end.2013.0703

    Article  PubMed  Google Scholar 

  36. Clements T, Messer JC, Terrell JD, Herman MP, Ng CK, Scherr DS et al (2012) High-grade ureteroscopic biopsy is associated with advanced pathology of upper-tract urothelial carcinoma tumors at definitive surgical resection. J Endourol 26:398–402. doi:10.1089/end.2011.0426

    Article  PubMed  Google Scholar 

  37. Rojas CP, Castle SM, Llanos CA, Santos Cortes JA, Bird V, Rodriguez S et al (2013) Low biopsy volume in ureteroscopy does not affect tumor biopsy grading in upper tract urothelial carcinoma. Urol Oncol 31:1696–1700. doi:10.1016/j.urolonc.2012.05.010

    Article  PubMed  Google Scholar 

  38. Smith AK, Stephenson AJ, Lane BR, Larson BT, Thomas AA, Gong MC et al (2011) Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management. Urology 78:82–86. doi:10.1016/j.urology.2011.02.038

    Article  PubMed  Google Scholar 

  39. Villa L, Cloutier J, Letendre J, Ploumidis A, Salonia A, Cornu J-N et al (2015) Early repeated ureteroscopy within 6-8 weeks after a primary endoscopic treatment in patients with upper tract urothelial cell carcinoma: preliminary findings. World J Urol. doi:10.1007/s00345-015-1753-7

    Google Scholar 

  40. Sung HH, Jeon HG, Han DH, Jeong BC, Il Seo S, Lee HM et al (2015) Diagnostic ureterorenoscopy is associated with increased intravesical recurrence following radical nephroureterectomy in upper tract urothelial carcinoma. PLoS ONE 10:e0139976. doi:10.1371/journal.pone.0139976

    Article  PubMed  PubMed Central  Google Scholar 

  41. Lee JK, Kim KB, Park YH, Oh JJ, Lee S, Jeong CW et al (2016) Correlation between the timing of diagnostic ureteroscopy and intravesical recurrence in upper tract urothelial cancer. Clin Genitourin Cancer 14:e37–e41. doi:10.1016/j.clgc.2015.07.008

    Article  PubMed  Google Scholar 

  42. Nison L, Rouprêt M, Bozzini G, Ouzzane A, Audenet F, Pignot G et al (2013) The oncologic impact of a delay between diagnosis and radical nephroureterectomy due to diagnostic ureteroscopy in upper urinary tract urothelial carcinomas: results from a large collaborative database. World J Urol 31:69–76. doi:10.1007/s00345-012-0959-1

    Article  PubMed  Google Scholar 

  43. Kleinmann N, Healy KA, Hubosky SG, Margel D, Bibbo M, Bagley DH (2013) Ureteroscopic biopsy of upper tract urothelial carcinoma: comparison of basket and forceps. J Endourol 27:1450–1454. doi:10.1089/end.2013.0220

    Article  PubMed  Google Scholar 

  44. Traxer O, Geavlete B, de Medina SGD, Sibony M, Al-Qahtani SM (2011) Narrow-band imaging digital flexible ureteroscopy in detection of upper urinary tract transitional-cell carcinoma: initial experience. J Endourol 25:19–23. doi:10.1089/end.2009.0593

    Article  PubMed  Google Scholar 

  45. Kata SG, Aboumarzouk OM, Zreik A, Somani B, Ahmad S, Nabi G et al (2016) Photodynamic diagnostic ureterorenoscopy: a valuable tool in the detection of upper urinary tract tumour. Photodiagn Photodyn Ther 13:255–260. doi:10.1016/j.pdpdt.2015.08.002

    Article  Google Scholar 

  46. Bus MTJ, Muller BG, de Bruin DM, Faber DJ, Kamphuis GM, van Leeuwen TG et al (2013) Volumetric in vivo visualization of upper urinary tract tumors using optical coherence tomography: a pilot study. J Urol 190:2236–2242. doi:10.1016/j.juro.2013.08.006

    Article  PubMed  Google Scholar 

  47. Matin SF, Kamat AM, Grossman HB (2010) High-frequency endoluminal ultrasonography as an aid to the staging of upper tract urothelial carcinoma: imaging findings and pathologic correlation. J Ultrasound Med 29:1277–1284

    Article  PubMed  Google Scholar 

  48. Bui D, Mach KE, Zlatev DV, Rouse RV, Leppert JT, Liao JC (2015) A pilot study of in vivo confocal laser endomicroscopy of upper tract urothelial carcinoma. J Endourol 29:1418–1423. doi:10.1089/end.2015.0523

    Article  PubMed  PubMed Central  Google Scholar 

  49. Lughezzani G, Burger M, Margulis V, Matin SF, Novara G, Roupret M et al (2012) Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature. Eur Urol 62:100–114. doi:10.1016/j.eururo.2012.02.030

    Article  PubMed  Google Scholar 

  50. Xylinas E, Kluth LA, Rieken M, Lee RK, Elghouayel M, Ficarra V et al (2014) Impact of smoking status and cumulative exposure on intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy. BJU Int 114:56–61. doi:10.1111/bju.12400

    Article  PubMed  Google Scholar 

  51. Messer JC, Terrell JD, Herman MP, Ng CK, Scherr DS, Scoll B et al (2013) Multi-institutional validation of the ability of preoperative hydronephrosis to predict advanced pathologic tumor stage in upper-tract urothelial carcinoma. Urol Oncol 31:904–908. doi:10.1016/j.urolonc.2011.07.011

    Article  PubMed  Google Scholar 

  52. Chung PH, Krabbe L-M, Darwish OM, Westerman ME, Bagrodia A, Gayed BA et al (2014) Degree of hydronephrosis predicts adverse pathological features and worse oncologic outcomes in patients with high-grade urothelial carcinoma of the upper urinary tract. Urol Oncol 32:981–988. doi:10.1016/j.urolonc.2014.02.018

    Article  PubMed  Google Scholar 

  53. Isbarn H, Jeldres C, Shariat SF, Liberman D, Sun M, Lughezzani G et al (2009) Location of the primary tumor is not an independent predictor of cancer specific mortality in patients with upper urinary tract urothelial carcinoma. J Urol 182:2177–2181. doi:10.1016/j.juro.2009.07.035

    Article  PubMed  Google Scholar 

  54. Raman JD, Ng CK, Scherr DS, Margulis V, Lotan Y, Bensalah K et al (2010) Impact of tumor location on prognosis for patients with upper tract urothelial carcinoma managed by radical nephroureterectomy. Eur Urol 57:1072–1079. doi:10.1016/j.eururo.2009.07.002

    Article  PubMed  Google Scholar 

  55. Chromecki TF, Cha EK, Fajkovic H, Margulis V, Novara G, Scherr DS et al (2012) The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy. Eur Urol 61:245–253. doi:10.1016/j.eururo.2011.09.017

    Article  PubMed  Google Scholar 

  56. Remzi M, Haitel A, Margulis V, Karakiewicz P, Karakiewizc P, Montorsi F et al (2009) Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients. BJU Int 103:307–311. doi:10.1111/j.1464-410X.2008.08003.x

    Article  PubMed  Google Scholar 

  57. Brien JC, Shariat SF, Herman MP, Ng CK, Scherr DS, Scoll B et al (2010) Preoperative hydronephrosis, ureteroscopic biopsy grade and urinary cytology can improve prediction of advanced upper tract urothelial carcinoma. J Urol 184:69–73. doi:10.1016/j.juro.2010.03.030

    Article  PubMed  Google Scholar 

  58. Favaretto RL, Shariat SF, Savage C, Godoy G, Chade DC, Kaag M et al (2012) Combining imaging and ureteroscopy variables in a preoperative multivariable model for prediction of muscle-invasive and non-organ confined disease in patients with upper tract urothelial carcinoma. BJU Int 109:77–82. doi:10.1111/j.1464-410X.2011.10288.x

    Article  PubMed  Google Scholar 

  59. Margulis V, Youssef RF, Karakiewicz PI, Lotan Y, Wood CG, Zigeuner R et al (2010) Preoperative multivariable prognostic model for prediction of nonorgan confined urothelial carcinoma of the upper urinary tract. J Urol 184:453–458. doi:10.1016/j.juro.2010.03.142

    Article  PubMed  Google Scholar 

  60. Rouprêt M, Colin P, Yates DR (2014) A new proposal to risk stratify urothelial carcinomas of the upper urinary tract (UTUCs) in a predefinitive treatment setting: low-risk versus high-risk UTUCs. Eur Urol 66:181–183. doi:10.1016/j.eururo.2013.12.007

    Article  PubMed  Google Scholar 

Download references

Authors’ contribution

Thalmann GN and Shariat SF were involved in protocol/project development; Soria F, Shariat SF, Lerner SP, Fritsche H, Rink M, Kassouf W, Spiess PE, Lotan Y, Ye D, Fernández MI, Kikuchi E, Chade DC, Babjuk M, Grollman AP and Thalmann GN were involved in data collection or management; Soria F, Shariat SF, Thalmann GN, Data analysis; Soria F, Shariat SF and Thalmann GN wrote the manuscript; Soria F, Shariat SF, Lerner SP, Fritsche H, Rink M, Kassouf W, Spiess PE, Lotan Y, Ye D, Fernández MI, Kikuchi E, Chade DC, Babjuk M, Grollman AP and Thalmann GN wrote and edited the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to George N. Thalmann.

Ethics declarations

Conflict of interest

I certify that all conflicts of interest including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript are the following: Shahrokh Shariat owns or co-owns the following patents: Methods to determine prognosis after therapy for prostate cancer. Granted 2002-09-06. Methods to determine prognosis after therapy for bladder cancer. Granted 2003-06-19. Prognostic methods for patients with prostatic disease. Granted 2004-08-05. Soluble Fas: urinary marker for the detection of bladder transitional cell carcinoma. Granted 2010-07-20. He is advisory board member of Astellas, Cepheid, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanofi, Wolff. He is speaker for Astellas, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanochemia, Sanofi, Wolff.

Ethical standards

This study was conducted according to the Declaration of Helsinki.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Soria, F., Shariat, S.F., Lerner, S.P. et al. Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC). World J Urol 35, 379–387 (2017). https://doi.org/10.1007/s00345-016-1928-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-016-1928-x

Keywords

Navigation