New Diagnostic Endoscopic Techniques for Upper Urinary Tract Urothelial Carcinoma

  • Maria Teresa Vieira Universidade do Porto - Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal
  • Vítor Cavadas Universidade do Porto - Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal; Serviço de Urologia, Centro Hospitalar do Porto - Hospital de Santo António, Porto, Portugal
Keywords: Image Enhancement, Urinary Tract/diagnostic imaging, Urologic Neoplasms/diagnostic imaging


Upper tract urothelial carcinoma (UTUC) is uncommon, but most cases are invasive at diagnosis. Standard of care in patients with UTUC is radical nephroureterectomy (RNU), but low risk UTUC can be treated with kidney sparing surgery (KSS) without compromising oncological outcomes. Current diagnostic techniques have many limitations on UTUC diagnosis, mainly in the detection of carcinoma in situ (CIS), a flat, high grade lesion with high progression risk. Therefore, investigating new diagnostic techniques which allow earlier detection of UTUC lesions has become a relevant matter.

This review provides an overview of the new imaging diagnostic techniques currently available for UTUC diagnosis. A PubMed literature search was performed and articles on narrow band imaging (NBI), Image1 S, photodynamic diagnosis (PDD), confocal laser endomicroscopy (CLE) and optical coherence tomography (OCT) were reviewed.

Six articles were selected for review, all of them referring to in vivo human studies. There were no articles on Image1 S. All techniques are compatible with existing flexible ureterorenoscopes. NBI, Image1 S and PDD aim at improving UTUC detection. CLE and OCT aim at providing minimally invasive and real-time histopathological diagnostic. Either NBI or PDD show a better lesion detection rate in comparison with conventional flexible ureterorenoscopy (FURS), but only PDD has shown a better CIS detection. CLE can differentiate healthy from malignant urothelium and high grade lesions from low grade ones. However, it does not allow staging. OCT shows higher UTUC staging and grading sensitivity than biopsy, but lesions greater than 2 mm can cause false-positives.

Combining FURS with new diagnostic techniques could improve its diagnostic precision and capability to properly select KSS candidates. Further research needs to be conducted to validate these new diagnostic techniques on the UTUC diagnosis.


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1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67: 7–30. doi: 10.3322/caac.21387.

2. Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM, et al. EAU guidelines on non–muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017; 71: 447-61. doi: 10.1016/j.eururo. 2016.05.041

3. 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: 1224-33. doi: 10.1002/cncr.24135.

4. Cosentino M, Palou J, Gaya JM, Breda A, Rodriguez-Faba O, Villavicencio-Mavrich H. Upper urinary tract urothelial cell carcinoma: location as a predictive factor for concomitant bladder carcinoma. World J Urol. 2013;
31: 141-5. doi: 10.1007/s00345-012-0877-2.

5. Rouprêt M, Babjuk M, Compérat 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: 111-22. doi: 10.1016/j.

6. Fang D, Seisen T, Yang K, Liu P, Fan X, Singla N, et al. A systematic review and meta-analysis of oncological and renal function outcomes obtained after segmental ureterectomy versus radical nephroureterectomy
for upper tract urothelial carcinoma. Eur J Surg Oncol. 2016; 42: 1625-35. doi: 10.1016/j.ejso.2016.08.008.

7. Audenet F, Traxer O, Yates DR, Cussenot O, Rouprêt M. Potential role of photodynamic techniques combined with new generation flexible ureterorenoscopes and molecular markers for the management of urothelial
carcinoma of the upper urinary tract. BJU Int. 2012; 109: 608-13. doi:

8. 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: 614-28. doi:

9. Razavi SA, Sadigh G, Kelly AM, Cronin P. Comparative effectiveness of imaging modalities for the diagnosis of upper and lower urinary tract malignancy: a critically appraised topic. Acad Radiol. 2012; 19: 1134-40.
doi: 10.1016/j.acra.2012.05.004.

10. Baard J, de Bruin DM, Zondervan PJ, Kamphuis G, de la Rosette J, Laguna MP. Diagnostic dilemmas in patients with upper tract urothelial carcinoma. Nat Rev Urol. 2017; 14: 181-91. doi: 10.1038/nrurol.2016.252.

11. Xu AD, Ng CS, Kamat A, Grossman HB, Dinney C, Sandler CM. Significance of upper urinary tract urothelial thickening and filling defect seen on MDCT urography in patients with a history of urothelial neoplasms. AJR
Am J Roentgenol. 2010; 195: 959-65. doi: 10.2214/AJR.09.4177.

12. Renshaw AA. Comparison of ureteral washing and biopsy specimens in the community setting. Cancer. 2006; 108: 45-8.

13. Sedlock DJ, MacLennan GT. Urine cytology in the evaluation of upper tract urothelial lesions. J Urol. 2004; 172: 2406.

14. Williams SK, Denton KJ, Minervini A, Oxley J, Khastigir J, Timoney AG, et al. Correlation of upper-tract cytology, retrograde pyelography, ureteroscopic appearance, and ureteroscopic biopsy with histologic examination of upper-tract transitional cell carcinoma. J Endourol. 2008; 22: 71-6. doi: 10.1089/end.2007.9853.

15. Tavora F, Fajardo DA, Lee TK, Lotan T, Miller JS, Miyamoto H, et al. Small endoscopic biopsies of the ureter and renal pelvis: pathologic pitfalls. Am J Surg Pathol. 2009; 33: 1540-6. doi: 10.1097/PAS.0b013e3181aec42a.

16. Straub J, Strittmatter F, Karl A, Stief CG, Tritschler S. Ureterorenoscopic biopsy and urinary cytology according to the 2004 WHO classification underestimate tumor grading in upper urinary tract urothelial carcinoma.
Urol Oncol. 2013; 31: 1166-70. doi: 10.1016/j.urolonc.2011.12.021.

17. Wang JK, Tollefson MK, Krambeck AE, Trost LW, Thompson RH. High rate of pathologic upgrading at nephroureterectomy for upper tract urothelial carcinoma. Urology. 2012; 79: 615-9. doi: 10.1016/j.urology.2011.11.049.

18. 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: 82-6. doi:

19. Guarnizo E, Pavlovich CP, Seiba M, Carlson DL, Vaughan ED, Sosa RE. Ureteroscopic biopsy of upper tract urothelial carcinoma: improved diagnostic accuracy and histopathological considerations using a multi-biopsy
approach. J Urol. 2000; 163: 52-5.

20. Skolarikos A, Griffiths TRL, Powell PH, Thomas DJ, Neal DE, Kelly JD. Cytologic analysis of ureteral washings is informative in patients with grade 2 upper tract TCC considering endoscopic treatment. Urology. 2003; 61:

21. Cauberg EC, de Bruin DM, Faber DJ, van Leeuwen TG, de la Rosette JJ, de Reijke TM. A new generation of optical diagnostics for bladder cancer: technology, diagnostic accuracy, and future applications. Eur Urol. 2009;
56: 287-97. doi: 10.1016/j.eururo.2009.02.033.

22. Liu JJ, Droller MJ, Liao JC. New optical imaging technologies for bladder cancer: considerations and perspectives. J Urol. 2012; 188: 361-8. doi: 10.1016/j.juro.2012.03.127.

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

24. Kata SG, Aboumarzouk OM, Zreik A, Somani B, Somani B, Ahmad S, Nabi G, et al. Photodynamic diagnostic ureterorenoscopy: A valuable tool in the detection of upper urinary tract tumour. Photodiagnosis Photodyn Ther
2016; 13: 255-60. doi: 10.1016/j.pdpdt.2015.08.002

25. Villa L, Cloutier J, Cotè JF, Salonia A, Montorsi F, Traxer O. Confocal laser encomicroscopy in the management of endoscopically treated upper urinary tract transitional cell carcinoma: preliminary data. J Endourol. 2016;
30: 237-42. doi: 10.1089/end.2015.0644.

26. Bui D, Mach KE, Zlatev DV, Rouse RV, Leppert JT, Liao JC. A pilot study of in vivo confocal laser endomicroscopy pf upper tract urothelial carcinoma. J Endourol. 2015; 29: 1418-23. doi: 10.1089/end.2015.0523.

27. Breda A, Territo A, Guttilla A, Sanguedolce F, Manfredi M, Quaresima L, et al. Correlation between confocal laser endomicroscopy (Cellvizio®) and histological grading of upper tract urothelial carcinoma: a step forward for a better selection of patients suitable for conservative management. Eur Urol Focus 2017 (in press) doi: 10.1016/j.euf.2017.05.008.

28. Bus MTJ, de Bruin DM, Faber DJ, Kamphuis GM, Zondervan PJ, Laguna-Pes MP, et al. Optical coherence tomography as a tool for in vivo staging and grading of upper urinary tract urothelial carcinoma: a study of diagnostic accuracy. J Urol. 2016; 196: 1749-55. doi: 10.1016/j.juro.2016.04.117.

29. Bryan RT, Billingham LJ, Wallace DM. Narrow-band imaging flexible cystoscopy in the detection of recurrent urothelial cancer of the bladder. BJU Int. 2008; 101: 702-6.

30. Bus MT, de Bruin DM, Faber DJ, Kamphuis GM, Zondervan PJ, Laguna Pes MP, et al. Optical diagnostics for upper urinary tract urothelial cancer: technology, thresholds, and clinical applications. J Endourol 2015; 29: 113-23. doi: 10.1089/end.2014.0551.

31. Cauberg EC, Mamoulakis C, de la Rosette JJ, de Reijke TM. Narrow band imaging-assisted transurethral resection for non-muscle invasive bladder cancer significantly reduces residual tumour rate. World J Urol. 2011; 29: 503-9. doi: 10.1007/s00345-011-0659-2.

32. Herr HW, Donat SM. Reduced bladder tumour recurrence rate associated with narrow-band imaging surveillance cystoscopy. BJU Int. 2011; 107: 396-8. doi: 10.1111/j.1464-410X.2010.09547.x.

33. Naselli A, Introini C, Timossi L. A randomized prospective trial to assess the impact of transurethral resection in narrow band imaging modality on non–muscle-invasive bladder cancer recurrence. Eur Urol. 2012; 61: 908-
13. doi: 10.1016/j.eururo.2012.01.018.

34. Herr HW. Randomized Trial of Narrow-band Versus White-light Cystoscopy for Restaging (Second-look) Transurethral Resection of Bladder Tumors. Eur Urol. 2015; 67: 605-8. doi: 10.1016/j.eururo.2014.06.049

35. Tatsugami K, Kuroiwa K, Kamoto T, Nishiyama H, Watanabe J, Ishikawa S, et al. Evaluation of narrow-band imaging as a complementary method for the detection of bladder cancer. J Endourol. 2010; 24: 1807-11. doi:

36. Li K, Lin T, Fan X, Duan Y, Huang J. Diagnosis of narrow-band imaging in non-muscle-invasive bladder cancer: A systematic review and meta-analysis. Int J Urol. 2013; 20: 602-9. doi: 10.1111/j.1442-2042.2012.03211.x.

37. Herr HW, Donat SM. A comparison of white-light cystoscopy and narrow-band imaging cystoscopy to detect bladder tumour recurrences. BJU Int. 2008; 102: 1111-4. doi: 10.1111/j.1464-410X.2008.07846.x.

38. Geavlete B, Multescu R, Georgescu D, Stanescu F, Jecu M, Geavlete P. Narrow band imaging cystoscopy and bipolar plasma vaporization for large nonmuscle-invasive bladder tumors—results of a prospective, randomized
comparison to the standard approach. Urology. 2012; 79: 846-52. doi: 10.1016/j.urology.2011.08.081.

39. Kamphuis GM, de Bruin DM, Brandt MJ, Knoll T, Conort P, Lapini A, et al. Comparing image perception of bladder tumors in four different Storz professional image enhancement system modalities using the íSPIES App.
J Endourol. 2016; 30: 602-8. doi: 10.1089/end.2015.0687.

40. Gravas S, Stenzl A. The Storz professional image enhancement system (SPIES) non muscle-invasive bladder cancer study: a multicenter international randomized controlled study. J Endourol. 2014; 28: 1254-5.

41. 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: 1214-21. doi: 10.1016/j.juro.2012.05.079.

42. Somani BK, Moseley H, Eljamel MS, Nabi G, Kata SG. Photodynamic diagnosis (PDD) for upper urinary tract transitional cell carcinoma (UT-TCC): evolution of a new technique. Photodiagnosis Photodyn Ther. 2010; 7: 39-
43. doi: 10.1016/j.pdpdt.2009.12.005.

43. Ahmad S, Aboumarzouk O, Somani B, Nabi G, Kata SG. Oral 5-aminolevulinic acid in simultaneous photodynamic diagnosis of upper and lower urinary tract transitional cell carcinoma – a prospective audit. BJU Int. 2012; 110 :E596-600. doi: 10.1111/j.1464-410X.2012.11326.x.

44. 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: 138-42. doi:

45. Aboumarzouk OM, Mains E, Moseley H, Kata SG. Diagnosis of upper urinary tract tumours: is photodynamic diagnosis assisted ureterorenoscopy required as an addition to modern imaging and ureterorenoscopy? Photodiagnosis Photodyn Ther. 2013; 10: 127-33. doi: 10.1016/j.pdpdt.2012.11.008.

46. Mowatt G, N'Dow J, Vale L, Nabi G, Boachie C, Cook JA, et al. Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: Systematic review and meta-analysis. Int J Technol Assess Health Care.
2011; 27: 3-10. doi: 10.1017/S0266462310001364

47. Cheng L, Cheville JC, Neumann RM, Bostwick DG. Natural history of urothelial dysplasia of the bladder. Am J Surg Pathol .1999; 23: 443-7.

48. Baard J, Freund JE, de la Rosette JJ, Laguna MP. New technologies for upper tract urothelial carcinoma management. Curr Opin Urol. 2017; 27: 170-5. doi: 10.1097/MOU.0000000000000373.

49. 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: 437. doi: 10.1007/s11934-014-0437-y.

50. Sonn GA, Jones SNE, Tarin TV, Hsiao ST, Jensen KC, Liao JC. Optical biopsy of human bladder neoplasia with in vivo confocal laser endomicroscopy. J Urol. 2009; 182: 1299-305. doi: 10.1089/end.2010.0686.

51. Adams W, Wu K, Liu JJ, Hsiao STT, Jensen KC, Liao JC. Comparison of 2.6-and 1.4-mm imaging probes for confocal laser endomicroscopy of the urinary tract. J Endourol. 2011; 25: 917-21. doi: 10.1089/end.2010.0686

52. 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. Urology2011; 78: 225-31. doi: 10.1016/j.urology.2011.02.057.

53. Chang TC, Liu JJ, Hsiao ST, Pan Y, Mach KE, Leppert JT, et al. Interobserver agreement of confocal laser endomicroscopy for bladder cancer. J Endourol. 2013; 27: 598-603. doi: 10.1089/end.2012.0549.

54. Liem EI, Freund JE, Baard J et al. Confocal Laser Endomicroscopy for the Diagnosis of urothelial carcinoma in the bladder and the upper urinary tract: protocols for two prospective explorative studies. JMIR Res Protoc.
2018;7:e34. doi: 10.2196/resprot.8862.

55. André B, Vercauteren T, Buchner AM, Krishna M, Ayache N, Wallace MB. Software for automated classification of probe-based confocal laser endomicroscopy videos of colorectal polyps. World J Gastroenterol. 2012; 18:
5560-9. doi: 10.3748/wjg.v18.i39.5560.

56. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical coherence tomography. Science. 1991; 254: 1178-81.

57. Wessels R, De Bruin DM, Faber DJ, Van Leeuwen TG, Van Beurden M, Ruers TJ. Optical biopsy of epithelial cancers by optical coherence tomography (OCT). Lasers Med Sci. 2014; 29: 1297-305. doi: 10.1007/s10103-

58. 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: 2259-64.

59. Wang H, Kang W, Zhu H, MacLennan G, Rollins AM. Three-dimensional imaging of ureter with endoscopic optical coherence tomography. Urology. 2011; 77: 1254-8. doi: 10.1016/j.urology.2010.11.044.

60. Hermes B, Spöler F, Naami A, Bornemann J, Först M, Grosse J, et al. Visualization of the basement membrane zone of the bladder by optical coherence tomography: feasibility of noninvasive evaluation of tumor invasion.
Urology. 2008; 72: 677-81. doi: 10.1016/j.urology.2008.02.062.

61. Wessels R, De Bruin DM, Faber DJ, Horenblas S, van Rhijn BW, Vincent AD, et al. Optical coherence tomography accurately identifies patients with penile (pre) malignant lesions: A single center prospective study. Urol Ann. 2015; 7: 459. doi: 10.4103/0974-7796.156147.

62. Barwari K, de Bruin DM, Cauberg EC, Faber DJ, van Leeuwen TG, Wijkstra H, et al. Advanced diagnostics in renal mass using optical coherence tomography: a preliminary report. J Endourol. 2011; 25: 311-5. doi: 10.1089/

63. Xie TQ, Zeidel ML, Pan YT. Detection of tumorigenesis in urinary bladder with optical coherence tomography: optical characterization of morphological changes. Opt Express. 2002; 10: 1431-43.

64. Schmidbauer J, Remzi M, Klatte T, Waldert M, Mauermann J, Susani M, et al. Fluorescence cystoscopy with high-resolution optical coherence tomography imaging as an adjunct reduces false-positive findings in the diagnosis of urothelial carcinoma of the bladder. Eur Urol. 2009; 56: 914-9. doi: