Upper Urinary Tract Carcinoma In Situ

  • Jay D. RamanEmail author
  • Joshua L. Warrick
  • Grant P. Redrow
  • Surena F. Matin


Upper tract carcinoma in situ (UTCIS) is a non-muscle invasive, high-grade cancer involving the epithelial lining of the renal pelvis, calyces, and ureter. While progression to muscle invasion or metastasis occurs infrequently, UTCIS remains a vexing clinical conundrum for diagnosis, therapy, and subsequent surveillance. Organ preservation remains a central tenet in the management of UTCIS with topical intracavitary instillation playing a critical role to achieve this goal. Nonetheless, owing to the uncommon presentation of UTCIS, treatment paradigms and algorithms are often extrapolated from management of bladder CIS. In that regard, acknowledging that the clinical behavior between these two entities is distinct, prospective evaluation focusing on the UTCIS patient cohort is critical for the future.


Urothelial carcinoma Upper tract Carcinoma in situ (CIS) BCG 


  1. 1.
    Raman JD, Scherr DS. Management of patients with upper urinary tract transitional cell carcinoma. Nat Clin Pract Urol. 2007;4(8):432–43.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 3.
    Herr HW. Durable response of a carcinoma in situ of the renal pelvis to topical bacillus Calmette-Guerin. J Urol. 1985;134(3):531–2.PubMedCrossRefGoogle Scholar
  4. 4.
    Nishino Y, Yamamoto N, Komeda H, Takahashi Y, Deguchi T. Bacillus Calmette-Guerin instillation treatment for carcinoma in situ of the upper urinary tract. BJU Int. 2000;85(7):799–801.PubMedCrossRefGoogle Scholar
  5. 5.
    Nonomura N, Ono Y, Nozawa M, Fukui T, Harada Y, Nishimura K, et al. Bacillus Calmette-Guerin perfusion therapy for the treatment of transitional cell carcinoma in situ of the upper urinary tract. Eur Urol. 2000;38(6):701–4; discussion 5.Google Scholar
  6. 6.
    Okubo K, Ichioka K, Terada N, Matsuta Y, Yoshimura K, Arai Y. Intrarenal bacillus Calmette-Guerin therapy for carcinoma in situ of the upper urinary tract: long-term follow-up and natural course in cases of failure. BJU Int. 2001;88(4):343–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Irie A, Iwamura M, Kadowaki K, Ohkawa A, Uchida T, Baba S. Intravesical instillation of bacille Calmette-Guerin for carcinoma in situ of the urothelium involving the upper urinary tract using vesicoureteral reflux created by a double-pigtail catheter. Urology. 2002;59(1):53–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Miyake H, Eto H, Hara S, Okada H, Kamidono S, Hara I. Clinical outcome of bacillus Calmette-Guerin perfusion therapy for carcinoma in situ of the upper urinary tract. Int J Urol: Official Journal of the Japanese Urological Association. 2002;9(12):677–80.CrossRefGoogle Scholar
  9. 9.
    Hayashida Y, Nomata K, Noguchi M, Eguchi J, Koga S, Yamashita S, et al. Long-term effects of bacille Calmette-Guerin perfusion therapy for treatment of transitional cell carcinoma in situ of upper urinary tract. Urology. 2004;63(6):1084–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Kojima Y, Tozawa K, Kawai N, Sasaki S, Hayashi Y, Kohri K. Long-term outcome of upper urinary tract carcinoma in situ: effectiveness of nephroureterectomy versus bacillus Calmette-Guerin therapy. Int J Urol: Official Journal of the Japanese Urological Association. 2006;13(4):340–4.CrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    Shapiro EY, Lipsky MJ, Cha DY, McKiernan JM, Benson MC, Gupta M. Outcomes of intrarenal Bacillus Calmette-Guerin/interferon-α2B for biopsy-proven upper-tract carcinoma in situ. J Endourol/Endourol Soc. 2012;26(12):1645–50.CrossRefGoogle Scholar
  13. 13.
    Traxer O, Geavlete B, de Medina SG, Sibony M, Al-Qahtani SM. Narrow-band imaging digital flexible ureteroscopy in detection of upper urinary tract transitional-cell carcinoma: initial experience. J Endourol/Endourol Soc. 2011;25(1):19–23.CrossRefGoogle Scholar
  14. 14.
    Aboumarzouk OM, Ahmad S, Moseley H, Kata SG. Accuracy of photodynamic diagnosis in the detection and follow-up of patients with upper urinary tract lesions: initial 3-year experience. Arab J Urol. 2012;10(2):138–42.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Mueller-Lisse UL, Meissner OA, Babaryka G, Bauer M, Eibel R, Stief CG, et al. Catheter-based intraluminal optical coherence tomography (OCT) of the ureter: ex-vivo correlation with histology in porcine specimens. Eur Radiol. 2006;16(10):2259–64.PubMedCrossRefGoogle Scholar
  16. 16.
    Matin SF, Kamat AM, Grossman HB. High-frequency endoluminal ultrasonography as an aid to the staging of upper tract urothelial carcinoma: imaging findings and pathologic correlation. J Ultrasound Med: Official Journal of the American Institute of Ultrasound in Medicine. 2010;29(9):1277–84.CrossRefGoogle Scholar
  17. 17.
    Wu K, Liu JJ, Adams W, Sonn GA, Mach KE, Pan Y, et al. Dynamic real-time microscopy of the urinary tract using confocal laser endomicroscopy. Urology. 2011;78(1):225–31.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Ren H, Park KC, Pan R, Waltzer WC, Shroyer KR, Pan Y. Early detection of carcinoma in situ of the bladder: a comparative study of white light cystoscopy, narrow band imaging, 5-ALA fluorescence cystoscopy and 3-dimensional optical coherence tomography. J Urol. 2012;187(3):1063–70.PubMedCrossRefGoogle Scholar
  19. 19.
    Bus MT, Muller BG, de Bruin DM, Faber DJ, Kamphuis GM, van Leeuwen TG, et al. Volumetric in vivo visualization of upper urinary tract tumors using optical coherence tomography: a pilot study. J Urol. 2013;190(6):2236–42.PubMedCrossRefGoogle Scholar
  20. 20.
    Chen SP, Liao JC. Confocal laser endomicroscopy of bladder and upper tract urothelial carcinoma: a new era of optical diagnosis? Curr Urol Rep. 2014;15(9):437.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Kleinmann N, Healy KA, Hubosky SG, Margel D, Bibbo M, Bagley DH. Ureteroscopic biopsy of upper tract urothelial carcinoma: comparison of basket and forceps. J Endourol/Endourol Soc. 2013;27(12):1450–4.CrossRefGoogle Scholar
  22. 22.
    Smith AK, Stephenson AJ, Lane BR, Larson BT, Thomas AA, Gong MC, et al. Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management. Urology. 2011;78(1):82–6.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Clements T, Messer JC, Terrell JD, Herman MP, Ng CK, Scherr DS, et al. High-grade ureteroscopic biopsy is associated with advanced pathology of upper-tract urothelial carcinoma tumors at definitive surgical resection. J Endourol/Endourol Soc. 2012;26(4):398–402.CrossRefGoogle Scholar
  24. 24.
    Messer JC, Terrell JD, Herman MP, Ng CK, Scherr DS, Scoll B, et al. Multi-institutional validation of the ability of preoperative hydronephrosis to predict advanced pathologic tumor stage in upper-tract urothelial carcinoma. Urol Oncol. 2013;31(6):904–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Sternberg IA, Keren Paz GE, Chen LY, Herr HW, Donat SM, Bochner BH, et al. Upper tract imaging surveillance is not effective in diagnosing upper tract recurrence in patients followed for nonmuscle invasive bladder cancer. J Urol. 2013;190(4):1187–91.PubMedCrossRefGoogle Scholar
  26. 26.
    Amin MB, Eble JN. Urological pathology. 1st ed., ix, 934 pp.Google Scholar
  27. 27.
    Epstein JI, Amin MB, Reuter VE, Epstein JI. Biopsy interpretation of the bladder. 2nd ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health; 2010. vii, 355 pp.Google Scholar
  28. 28.
    Comperat E, Jacquet SF, Varinot J, Conort P, Roupret M, Chartier-Kastler E, et al. Different subtypes of carcinoma in situ of the bladder do not have a different prognosis. Virchows Arch: An International Journal of Pathology. 2013;462(3):343–8.CrossRefGoogle Scholar
  29. 29.
    McKenney JK, Gomez JA, Desai S, Lee MW, Amin MB. Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion. Am J Surg Pathol. 2001;25(3):356–62.PubMedCrossRefGoogle Scholar
  30. 30.
    Green DA, Rink M, Xylinas E, Matin SF, Stenzl A, Roupret M, et al. Urothelial carcinoma of the bladder and the upper tract: disparate twins. J Urol. 2013;189(4):1214–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Cheng L, Cheville JC, Neumann RM, Leibovich BC, Egan KS, Spotts BE, et al. Survival of patients with carcinoma in situ of the urinary bladder. Cancer. 1999;85(11):2469–74.PubMedCrossRefGoogle Scholar
  32. 32.
    Chade DC, Shariat SF, Godoy G, Savage CJ, Cronin AM, Bochner BH, et al. Clinical outcomes of primary bladder carcinoma in situ in a contemporary series. J Urol. 2010;184(1):74–80.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Munoz JJ, Ellison LM. Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol. 2000;164(5):1523–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Xylinas E, Rink M, Margulis V, Karakiewicz P, Novara G, Shariat SF, et al. Multifocal carcinoma in situ of the upper tract is associated with high risk of bladder cancer recurrence. Eur Urol. 2012;61(5):1069–70.PubMedCrossRefGoogle Scholar
  35. 35.
    Wright JL, Hotaling J, Porter MP. Predictors of upper tract urothelial cell carcinoma after primary bladder cancer: a population based analysis. J Urol. 2009;181(3):1035–9; discussion 9.PubMedCrossRefGoogle Scholar
  36. 36.
    Krabbe LM, Lotan Y, Bagrodia A, Gayed BA, Darwish OM, Youssef RF, et al. Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract—is there evidence for discordant biology? J Urol. 2014;191(4):926–31.PubMedCrossRefGoogle Scholar
  37. 37.
    Zhang Z, Furge KA, Yang XJ, Teh BT, Hansel DE. Comparative gene expression profiling analysis of urothelial carcinoma of the renal pelvis and bladder. BMC Med Genomics. 2010;3:58.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Wheat JC, Weizer AZ, Wolf JS Jr, Lotan Y, Remzi M, Margulis V, et al. Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ confined urothelial carcinoma following radical nephroureterectomy. Urol Oncol. 2012;30(3):252–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Otto W, Shariat SF, Fritsche HM, Gupta A, Matsumoto K, Kassouf W, et al. 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. 2011;29(4):487–94.PubMedCrossRefGoogle Scholar
  41. 41.
    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.PubMedCrossRefGoogle Scholar
  42. 42.
    Roupret M, Babjuk M, Comperat E, Zigeuner R, Sylvester RJ, Burger M, et al. European association of urology guidelines on upper urinary tract urothelial cell carcinoma: 2015 update. Eur Urol. 2015;68(5):868–79.PubMedCrossRefGoogle Scholar
  43. 43.
    Raman JD. Kidney sparing surgery for upper-tract urothelial carcinoma. Minerva urologica e nefrologica (The Italian Journal of Urology and Nephrology). 2016.Google Scholar
  44. 44.
    Margulis V, Shariat SF, Matin SF, Kamat AM, Zigeuner R, Kikuchi E, et al. Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer. 2009;115(6):1224–33.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Karam JA, Margulis V, Montorsi F, Karakiewicz PI, Lotan Y, Kikuchi E, et al. Carcinoma in situ of the upper urinary tract treated with radical nephroureterectomy—results from a multicenter study. Eur Urol. 2008;54(4):961–3.PubMedCrossRefGoogle Scholar
  46. 46.
    Morales A, Eidinger D, Bruce AW. Intracavitary bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180–3.PubMedCrossRefGoogle Scholar
  47. 47.
    Pollard ME, Levinson AW, Shapiro EY, Cha DY, Small AC, Mohamed NE, et al. Comparison of 3 upper tract anticarcinogenic agent delivery techniques in an ex vivo porcine model. Urology. 2013;82(6):1451 e1–6.CrossRefGoogle Scholar
  48. 48.
    Lamm DL. Preventing progression and improving survival with BCG maintenance. Eur Urol. 2000;37(Suppl 1):9–15.PubMedCrossRefGoogle Scholar
  49. 49.
    Lamm DL, Blumenstein BA, Crissman JD, Montie JE, Gottesman JE, Lowe BA, et al. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol. 2000;163(4):1124–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Sylvester RJ, van der MA, Lamm DL. Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol. 2002;168(5):1964–70.PubMedCrossRefGoogle Scholar
  51. 51.
    Nunez-Nateras R, Castle EP, Protheroe CA, Stanton ML, Ocal TI, Ferrigni EN, et al. Predicting response to bacillus Calmette-Guerin (BCG) in patients with carcinoma in situ of the bladder. Urol Oncol. 2014;32(1):45 e23–30.CrossRefGoogle Scholar
  52. 52.
    Ponticiello A, Perna F, Maione S, Stradolini M, Testa G, Terrazzano G, et al. Analysis of local T lymphocyte subsets upon stimulation with intravesical BCG: a model to study tuberculosis immunity. Respir Med. 2004;98(6):509–14.PubMedCrossRefGoogle Scholar
  53. 53.
    Schnapp DS, Weiss GH, Smith AD. Fever following intracavitary bacillus Calmette-Guerin therapy for upper tract transitional cell carcinoma. J Urol. 1996;156(2 Pt 1):386–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Jay D. Raman
    • 1
    Email author
  • Joshua L. Warrick
    • 2
  • Grant P. Redrow
    • 3
  • Surena F. Matin
    • 4
  1. 1.Division of UrologyPenn State Milton S. Hershey Medical CenterHersheyUSA
  2. 2.Department of PathologyPenn State Milton S. Hershey Medical CenterHersheyUSA
  3. 3.Department of Surgery (Urology)University of Texas HoustonHoustonUSA
  4. 4.Department of UrologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA

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