Skip to main content

Advertisement

SpringerLink
Log in

Optimal Management of Upper Tract Urothelial Carcinoma: an Unmet Need

  • Genitourinary Cancers (S Gupta, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Upper tract urothelial carcinoma (UTUC) is a rare genitourinary entity of the renal pelvis and the ureter characterized by a more aggressive disease phenotype when compared with urothelial carcinoma of the bladder (UCB) with more than half of UTUC cases presenting with invasive disease at diagnosis compared to 20% for bladder tumors. There is growing evidence suggesting that its distinct natural history from that of bladder cancer can be related to several genetic and epigenetic differences. Treatment of low-risk disease consists of kidney-sparing surgeries such as ureteroscopic and percutaneous treatments, segmental ureterectomy, and adjuvant topical and intracavitary chemo-immunotherapies. The standard of care for high-risk non-metastatic disease remains radical nephroureterectomy and bladder cuff excision with increasing utilization rates of minimally invasive approaches leading to reduced morbidity without compromising outcomes while the role of lymphadenectomy is still being investigated. The prognosis of UTUC has been stagnant over the past decade highlighting the need for further studies on the role of multimodal therapy (neoadjuvant/adjuvant chemotherapy, immunotherapy, targeted therapy) to optimize management and improve outcomes.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.

    Article  PubMed  Google Scholar 

  2. Raman JD, Messer J, Sielatycki JA, Hollenbeak CS. Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA, 1973-2005. BJU Int. 2011;107(7):1059–64.

    Article  PubMed  Google Scholar 

  3. Leow JJ, Chong KT, Chang SL, Bellmunt J. Upper tract urothelial carcinoma: a different disease entity in terms of management. ESMO Open. 2016;1(6):e000126.

    Article  PubMed  Google Scholar 

  4. Sfakianos JP, Cha EK, Iyer G, Scott SN, Zabor EC, Shah RH, et al. Genomic characterization of upper tract urothelial carcinoma. Eur Urol. 2015;68(6):970–7. Using next-generation sequencing from 59 UTUC and 102 UCB patients, the authors identified similar mutations in both cancer types but at different frequencies indicating a potential need for unique management strategies.

  5. Moss TJ, Qi Y, Xi L, Peng B, Kim TB, Ezzedine NE, et al. Comprehensive genomic characterization of upper tract urothelial carcinoma. Eur Urol. 2017;72(4):641–9.

    Article  CAS  PubMed  Google Scholar 

  6. Campbell MT, Shah AY, Matin SF, Siefker-Radtke AO. Optimizing management of upper tract urothelial carcinoma. Urol Oncol. 2017;35(7):492–8.The authors present an interesting review of the current evidence for perioperative chemotherapy in UTUC as well as developments in the molecular classification of UTUC.

    Article  PubMed  Google Scholar 

  7. Roupret M, Babjuk M, Comperat E, Zigeuner R, Sylvester RJ, Burger M, et al. European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2017 update. Eur Urol. 2018;73(1):111–22.This 2017 update of the EAU guidelines on UTUC offers a great overview of the present evidence-based recommendations for UTUC management.

    Article  PubMed  Google Scholar 

  8. Verges DP, Lallas CD, Hubosky SG, Bagley DH Jr. Endoscopic treatment of upper tract urothelial carcinoma. Curr Urol Rep. 2017;18(4):31.

    Article  PubMed  Google Scholar 

  9. Seisen T, Peyronnet B, Dominguez-Escrig JL, Bruins HM, Yuan CY, Babjuk M, et al. Oncologic outcomes of kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel. Eur Urol. 2016;70(6):1052–68.In this systematic review by the EAU bladder cancer guidelines panel, the authors review the studies comparing kidney-sparing surgery vs. radical nephroureterectomy for UTC and found similar oncologic outcomes for low-risk tumors with ureteroscopic and percutaneous management. Selected patients with high-grade and invasive tumors could benefit from segmental ureterectomy.

  10. Lucca I, Leow JJ, Shariat SF, Chang SL. Diagnosis and management of upper tract urothelial carcinoma. Hematol Oncol Clin North Am. 2015;29(2):271–88 ix.

    Article  PubMed  Google Scholar 

  11. Hanna N, Sun M, Trinh QD, Hansen J, Bianchi M, Montorsi F, et al. Propensity-score-matched comparison of perioperative outcomes between open and laparoscopic nephroureterectomy: a national series. Eur Urol. 2012;61(4):715–21.

    Article  PubMed  Google Scholar 

  12. Simone G, Papalia R, Guaglianone S, Ferriero M, Leonardo C, Forastiere E, et al. Laparoscopic versus open nephroureterectomy: perioperative and oncologic outcomes from a randomised prospective study. Eur Urol. 2009;56(3):520–6.

    Article  PubMed  Google Scholar 

  13. Capitanio U, Shariat SF, Isbarn H, Weizer A, Remzi M, Roscigno M, et al. Comparison of oncologic outcomes for open and laparoscopic nephroureterectomy: a multi-institutional analysis of 1249 cases. Eur Urol. 2009;56(1):1–9.

    Article  PubMed  Google Scholar 

  14. Ni S, Tao W, Chen Q, Liu L, Jiang H, Hu H, et al. Laparoscopic versus open nephroureterectomy for the treatment of upper urinary tract urothelial carcinoma: a systematic review and cumulative analysis of comparative studies. Eur Urol. 2012;61(6):1142–53.

    Article  PubMed  Google Scholar 

  15. Liu F, Guo W, Zhou X, Ding Y, Ma Y, Hou Y, et al. Laparoscopic versus open nephroureterectomy for upper urinary tract urothelial carcinoma: a systematic review and meta-analysis. Medicine (Baltimore). 2018;97(35):e11954.

    Article  Google Scholar 

  16. Chromecki TF, Bensalah K, Remzi M, Verhoest G, Cha EK, Scherr DS, et al. Prognostic factors for upper urinary tract urothelial carcinoma. Nat Rev Urol. 2011;8(8):440–7.

    Article  CAS  PubMed  Google Scholar 

  17. Gkougkousis EG, Mellon JK, Griffiths TR. Management of the distal ureter during nephroureterectomy for upper urinary tract transitional cell carcinoma: a review. Urol Int. 2010;85(3):249–56.

    Article  PubMed  Google Scholar 

  18. Xylinas E, Rink M, Cha EK, Clozel T, Lee RK, Fajkovic H, et al. Impact of distal ureter management on oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma. Eur Urol. 2014;65(1):210–7.

    Article  PubMed  Google Scholar 

  19. Nazzani S, Preisser F, Mazzone E, Tian Z, Mistretta FA, Soulieres D, et al. Nephroureterectomy with or without bladder cuff excision for localized urothelial carcinoma of the renal pelvis. Eur Urol Focus. 2018.

  20. Roscigno M, Brausi M, Heidenreich A, Lotan Y, Margulis V, Shariat SF, et al. Lymphadenectomy at the time of nephroureterectomy for upper tract urothelial cancer. Eur Urol. 2011;60(4):776–83.

    Article  PubMed  Google Scholar 

  21. Weight CJ, Gettman MT. The emerging role of lymphadenectomy in upper tract urothelial carcinoma. Urol Clin North Am. 2011;38(4):429–37 vi .

    Article  PubMed  Google Scholar 

  22. Matin SF, Sfakianos JP, Espiritu PN, Coleman JA, Spiess PE. Patterns of lymphatic metastases in upper tract urothelial carcinoma and proposed dissection templates. J Urol. 2015;194(6):1567–74.In this retrospective multi-institutional study from three NCI designated comprehensive cancer centers, the authors investigated the patterns of lymph node metastasis in 73 patients undergoing nephroureterectomy with lymphadenectomy and proposed a dissection templates according to laterality and location of the tumor within the upper urinary tract.

    Article  PubMed  Google Scholar 

  23. Seisen T, Shariat SF, Cussenot O, Peyronnet B, Renard-Penna R, Colin P, et al. Contemporary role of lymph node dissection at the time of radical nephroureterectomy for upper tract urothelial carcinoma. World J Urol. 2017;35(4):535–48.

    Article  CAS  PubMed  Google Scholar 

  24. Dominguez-Escrig JL, Peyronnet B, Seisen T, Bruins HM, Yuan CY, Babjuk M, et al. Potential benefit of lymph node dissection during radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review by the European Association of Urology Guidelines Panel on Non-muscle-invasive Bladder Cancer. Eur Urol Focus. 2017. https://doi.org/10.1016/j.euf.2017.09.015. In this systematic review by the EAU bladder cancer guidelines panel, the authors review the studies comparing nephrouretrectomy with or without lymphadenectomy and found that lymph node dissection improves survival in patients with high-stage renal pelvic tumors if performed in an anatomical template-based approach.

    Article  PubMed  Google Scholar 

  25. Guo R, Zhu Y, Xiong G, Li X, Zhang K, Zhou L. Role of lymph node dissection in the management of upper tract urothelial carcinomas: a meta-analysis. BMC Urol. 2018;18(1):24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Zigeuner RE, Hutterer G, Chromecki T, Rehak P, Langner C. Bladder tumour development after urothelial carcinoma of the upper urinary tract is related to primary tumour location. BJU Int. 2006;98(6):1181–6.

    Article  PubMed  Google Scholar 

  27. Novara G, De Marco V, Dalpiaz O, Gottardo F, Bouygues V, Galfano A, et al. Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract. BJU Int. 2008;101(11):1368–74.

    Article  PubMed  Google Scholar 

  28. Novara G, De Marco V, Dalpiaz O, Galfano A, Bouygues V, Gardiman M, et al. Independent predictors of contralateral metachronous upper urinary tract transitional cell carcinoma after nephroureterectomy: multi-institutional dataset from three European centers. Int J Urol. 2009;16(2):187–91.

    Article  PubMed  Google Scholar 

  29. Flaig TW, Spiess PE, Agarwal N, Bangs R, Boorjian SA, Buyyounouski MK, et al. NCCN Guidelines Insights: bladder cancer, version 5.2018. J Natl Compr Cancer Netw. 2018;16(9):1041–53.This 2018 update of the NCCN guidelines on bladder and upper tract cancer offers an overall review of the most recent studies and the present evidence-based recommendations for UTUC management.

  30. Cutress ML, Stewart GD, Wells-Cole S, Phipps S, Thomas BG, Tolley DA. Long-term endoscopic management of upper tract urothelial carcinoma: 20-year single-centre experience. BJU Int. 2012;110(11):1608–17.

    Article  PubMed  Google Scholar 

  31. Cutress ML, Stewart GD, Zakikhani P, Phipps S, Thomas BG, Tolley DA. Ureteroscopic and percutaneous management of upper tract urothelial carcinoma (UTUC): systematic review. BJU Int. 2012;110(5):614–28.

    Article  PubMed  Google Scholar 

  32. Keeley FX Jr, Bibbo M, Bagley DH. Ureteroscopic treatment and surveillance of upper urinary tract transitional cell carcinoma. J Urol. 1997;157(5):1560–5.

    Article  PubMed  Google Scholar 

  33. Giannarini G, Kessler TM, Birkhauser FD, Thalmann GN, Studer UE. Antegrade perfusion with bacillus Calmette-Guerin in patients with non-muscle-invasive urothelial carcinoma of the upper urinary tract: who may benefit? Eur Urol. 2011;60(5):955–60.

    Article  PubMed  Google Scholar 

  34. Donin NM, Duarte S, Lenis AT, Caliliw R, Torres C, Smithson A, et al. Sustained-release formulation of mitomycin C to the upper urinary tract using a thermosensitive polymer: a preclinical study. Urology. 2017;99:270–7.

    Article  PubMed  Google Scholar 

  35. Elalouf V, Xylinas E, Klap J, Pignot G, Delongchamps NB, Saighi D, et al. Bladder recurrence after radical nephroureterectomy: predictors and impact on oncological outcomes. Int J Urol. 2013;20(11):1078–83.

    Article  PubMed  Google Scholar 

  36. Fradet V, Mauermann J, Kassouf W, Rendon R, Jacobsen N, Fairey A, et al. Risk factors for bladder cancer recurrence after nephroureterectomy for upper tract urothelial tumors: results from the Canadian Upper Tract Collaboration. Urol Oncol. 2014;32(6):839–45.

    Article  PubMed  Google Scholar 

  37. Ishioka J, Saito K, Kijima T, Nakanishi Y, Yoshida S, Yokoyama M, et al. Risk stratification for bladder recurrence of upper urinary tract urothelial carcinoma after radical nephroureterectomy. BJU Int. 2015;115(5):705–12.

    Article  PubMed  Google Scholar 

  38. Xylinas E, Colin P, Audenet F, Phe V, Cormier L, Cussenot O, et al. Intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinomas: predictors and impact on subsequent oncological outcomes from a national multicenter study. World J Urol. 2013;31(1):61–8.

    Article  PubMed  Google Scholar 

  39. O’Brien T, Ray E, Singh R, Coker B, Beard R, British Association of Urological Surgeons Section of O. Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: a prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial). Eur Urol. 2011;60(4):703–10.

    Article  PubMed  Google Scholar 

  40. Ito A, Shintaku I, Satoh M, Ioritani N, Aizawa M, Tochigi T, et al. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013;31(11):1422–7.

    Article  CAS  PubMed  Google Scholar 

  41. Deng X, Yang X, Cheng Y, Liu X, Wu B, Wang Z, et al. Prognostic value and efficacy valuation of postoperative intravesical instillation in primary urothelial carcinomas of upper urinary tract. Int J Clin Exp Med. 2014;7(12):4734–46.

    PubMed  PubMed Central  Google Scholar 

  42. Lu DD, Boorjian SA, Raman JD. Intravesical chemotherapy use after radical nephroureterectomy: a national survey of urologic oncologists. Urol Oncol. 2017;35(3):113 e1–7.

    Article  Google Scholar 

  43. Wu P, Zhu G, Wei D, Liu S, Walsh K, Li D, et al. Prophylactic intravesical chemotherapy decreases bladder tumor recurrence after nephroureterectomy for primary upper tract urothelial carcinoma: a systematic review and meta-analysis. J BUON. 2015;20(5):1229–38.

    PubMed  Google Scholar 

  44. Leow JJ, Martin-Doyle W, Fay AP, Choueiri TK, Chang SL, Bellmunt J. A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma. Eur Urol. 2014;66(3):529–41.In this systematic review and meta-analysis, the authors demonstrated an overall survival and disease-free survival benefit for cisplatin-based adjuvant chemotherapy in UTUC. More trials are needed to confirm the utility of neoadjuvant systemic therapy.

    Article  PubMed  Google Scholar 

  45. Matin SF, Margulis V, Kamat A, Wood CG, Grossman HB, Brown GA, et al. Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer. 2010;116(13):3127–34.

    Article  PubMed  Google Scholar 

  46. Xylinas E, Rink M, Margulis V, Clozel T, Lee RK, Comploj E, et al. Impact of renal function on eligibility for chemotherapy and survival in patients who have undergone radical nephro-ureterectomy. BJU Int. 2013;112(4):453–61.

    Article  CAS  PubMed  Google Scholar 

  47. Browne RF, Meehan CP, Colville J, Power R, Torreggiani WC. Transitional cell carcinoma of the upper urinary tract: spectrum of imaging findings. Radiographics. 2005;25(6):1609–27.

    Article  PubMed  Google Scholar 

  48. Huang YC, Chang YH, Chiu KH, Shindel AW, Lai CH. Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma. Sci Rep. 2016;6:38175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hahn AW, Giri S, Pathak R, Bhatt VR, Martin MG. Effect of adjuvant radiotherapy on survival in patients with locoregional urothelial malignancies of the upper urinary tract. Anticancer Res. 2016;36(8):4051–5.

    CAS  PubMed  Google Scholar 

  50. Abbondanzo SJ, Chang SL. HIV-1 transgenic rats display alterations in immunophenotype and cellular responses associated with aging. PLoS One. 2014;9(8):e105256.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Ning YM, Maher VE, Beaver JA, Goldberg KB, Blumenthal GM, Pazdur R. Accelerating early access to immunotherapies for advanced urothelial carcinoma. Oncologist. 2018;23(2):139–42.

    Article  PubMed  Google Scholar 

  52. Plimack ER, Bellmunt J, Gupta S, Berger R, Chow LQ, Juco J, et al. Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study. Lancet Oncol. 2017;18(2):212–20.

    Article  CAS  PubMed  Google Scholar 

  53. Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016;17(11):1590–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Office 3155, Tampa, FL, 33612, USA

    Mounsif Azizi MD

  2. Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    Salim K. Cheriyan MD, Charles C. Peyton MD & Philippe E. Spiess MD, MS

  3. Department of Urology, Medical University of Vienna, Vienna, Austria

    Beat Foerster MD & Shahrokh F. Shariat MD

Authors
  1. Mounsif Azizi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Salim K. Cheriyan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Charles C. Peyton MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beat Foerster MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shahrokh F. Shariat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Philippe E. Spiess MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mounsif Azizi MD.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Genitourinary Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Azizi, M., Cheriyan, S.K., Peyton, C.C. et al. Optimal Management of Upper Tract Urothelial Carcinoma: an Unmet Need. Curr. Treat. Options in Oncol. 20, 40 (2019). https://doi.org/10.1007/s11864-019-0637-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-019-0637-2

Keywords

Search

Navigation