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| Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades |
Paul Gravestocka,Daniel Culluma,Bhaskar Somanib,Rajan Veeratterapillaya,*( )
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aUrology Department, Freeman Hospital, Newcastle Upon Tyne, UK
bDepartment of Urology, University Hospital Southampton, Southampton, UK |
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Abstract Objective: The role of ureteroscopy in the diagnosis of upper tract urothelial carcinoma is yet to be fully determined. We aimed to provide an up to date evaluation of its role and the emerging technologies in the field. Methods: A literature search of the last two decades (from 24th May, 2001 to 24th May, 2021) was carried out identifying 147 papers for potential inclusion within this narrative review. Results: Diagnostic ureteroscopy is undeniably useful in its ability to visualise and biopsy indeterminate lesions, and to risk stratify malignant lesions that may be suitable for kidney sparing surgery. However, an increased risk of intravesical recurrence following nephroureterectomy when a prior diagnostic ureteroscopy has been performed, inadequate sampling at biopsy, complications from the procedure, and difficult ureteric access are all potential drawbacks. Furthermore, whilst generally an accurate diagnostic procedure, it risks missing carcinoma in-situ lesions. Despite this, evidence shows that routine use of ureteroscopy changes the management of patients in a large proportion of cases, preventing unnecessary surgery or facilitating kidney sparing surgery. The overall rate of complications is low, and improved biopsy techniques and the use of tissue biomarkers for improved staging and grading are encouraging. The risks of delays to definitive management and post-ureteroscopy intravesical recurrence do not seem to affect survival, and trials are in progress to determine whether intravesical therapy can mitigate the latter. Further promising techniques are being investigated to improve shortcomings, particularly in relation to improved diagnosis of carcinoma in situ and preoperative staging. Conclusion: Ureteroscopy has a role in the diagnosis of upper tract malignancy, though whether it should be used routinely is yet to be determined.
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Received: 07 April 2022
Available online: 20 April 2024
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Corresponding Authors:
* E-mail address: rajan.veeratterapillay@doctors.org.uk (R. Veeratterapillay).
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| About author:: 1 Both authors contributed equally to this work. |
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The Preferred Reporting Items for Systematic reviews and Meta-Analyses diagram outlining study selection.
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| Study | Study period, range, year | Pt, n | Failed dURS, % | Non-diagnostic biopsy rate | Complication, n | | Wang et al., 2020 [23] | 2006-2018 | 65 | 14.8 | 5% | CD I: 3 | | Breda et al., 2019 [24] | 2015-2017 | 28 | - | 0-25.1%a | CD I: 1 | | Lama et al., 2018 [25] | 2011-2016 | 96 | - | 11%-19%a | - | | Hanna et al., 2017 [26] | 2004-2014 | 140 | - | 22% | - | | Grahn et al., 2017 [10] | 2005-2012 | 168b | 3.0 | - | - | | Yamany et al., 2015 [27] | 2005-2012 | 78 | - | 21% | - | | Tai et al., 2015 [28] | 2003-2007 | 52 | - | 4% | - | | Nita et al., 2014 [29] | 2008-2013 | 32 | - | 6% | - | | Kleinmann et al., 2013 [30] | 2008-2010 | 303 | - | 6%-37%a | - | | Shiraishi et al., 2003 [31] | 1995-2001 | 28 | - | 12% | CD I: 1 |
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Studies reporting complications including failed procedure or insufficient histology from biopsy samples.
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| Study | Study period, range, year | Grade | Stage | | Pt, n | Concordant, % | Upgraded, % | Downgraded, % | Pt, n | Concordant, % | Upstaged, % | | Cheaib et al., 2019 [34] | 2003-2018 | 191 | - | - | - | 191 | 70 | - | | Simon et al., 2019 [35] | 2000-2016 | 87 | 89 | 8 | 3 | 87 | 70 | 30 | | Breda et al., 2019 [24] | 2015-2017 | 28 | 68 | 32 | - | - | - | - | | Lama et al., 2018 [25] | 2011-2016 | 96 | 77 | - | - | - | - | - | | Hanna et al., 2017 [26] | 2004-2014 | 140 | - | 31 | - | 89 | - | 58 | | Dev et al., 2017 [36] | 2005-2014 | 45 | 43 | 44 | 10 | 39 | 32 | 63 | | Gillan et al., 2015 [37] | 2002-2013 | 92 | 43 | 12 | 12 | - | 39 | - | | Yamany et al., 2015 [27] | 2005-2012 | 78 | 82 | 17 | 1 | 72 | 33 | 65 | | Tai et al., 2015 [28] | 2003-2007 | 52 | 83 | 12 | 6 | - | - | - | | Nita et al., 2014 [29] | 2008-2013 | 32 | 84 | 16 | 0 | - | - | - | | Vashistha et al., 2013 [38] | 2008-2011 | 39 | 87 | - | - | 35 | 60 | - | | Rojas et al., 2013 [39] | 2002-2011 | 54 | 93 | 6 | 2 | 54 | 43 | 57 | | Wang et al., 2020 [23] | 1995-2008 | 136 | 61 | 34 | 5 | - | - | - | | Smith et al., 2011 [33] | 1992-2008 | 65 | 72 | - | - | 65 | 68 | - | | Williams et al., 2008 [40] | 1998-2006 | 28 | 64 | 32 | 3 | - | - | - | | Chitale et al., 2008 [41] | 1994-2004 | 19 | 90 | 5 | 5 | 19 | 79 | 16 | | Brown et al., 2007 [42] | 1986-2004 | 184 | 96 | - | - | - | - | - | | Shiraishi et al., 2003 [31] | 1995-2001 | 28 | 64 | 32 | 4 | - | - | - |
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Summary of studies reporting change in grade and stage of histology obtained from dURS biopsies compared to definitive pathology.
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| Study | Study period, range, year | Pt, n | FU, mean, month | Biopsy rate, % | IVR, % | CSS, % | OS, % | MFS, % | | dURS | No dURS | dURS | No dURS | dURS | No dURS | dURS | No dURS | | Shsm et al., 2021 [63] | 2012-2019 | 59 | 48.5 | - | 42.1 | 23.5 | - | - | - | - | - | - | | Sharma et al., 2021 [51] | 1995-2019 | 834 | 29.3a | 78 | 21.9 | 15 | - | - | - | - | - | - | | ?zol et al., 2021 [52] | 2005-2019 | 194 | 39.2 | 61 | 38.9 | 17.2 | - | - | - | - | - | - | | Chung et al., 2020 [53] | 2003-2018 | 453 | 41.5a | - | 43.8 | 26.9 | - | - | - | - | - | - | | Baboudjian et al., 2020 [58] | 2005-2017 | 93 | 35 | 89 | 41 | 26 | - | - | - | - | - | - | | Lee et al., 2018 [49] | 1990-2013 | 502 | 76.8 | 100 | - | - | 91.8 | 92.0 | 90.3 | 89.5 | 83.8 | 87.4 |
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Studies reporting IVR in patients undergoing dURS and RNU versus RNU alone.
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| Systematic review | Study, n | Pt, n | IVR (HR; 95% CI) | CSS (HR; 95% CI) | OS (HR) | MFS (HR) | Comment | | Tan et al., 2018 [62] | 11 | 4057 | 1.53; 1.31-1.77 | NSD | NSD | NSD | -8 studies analysed for IVR; 3 for CCS, OS, and MFS | | Guo et al., 2018 [61] | 8 | 3975 | 1.51; 1.29-1.77 | 0.76 (0.59-0.99) | NSD | NSD | -5 studies analysed for IVR, CSS and MFS; 2 for OS | | Marchioni et al., 2017 [59] | 7 | 2382 | 1.56; 1.33-1.88 | - | - | - | -6 studies analysed for IVR | | Liu et al., 2016 [54] | 9 | 3198 | 1.42; 1.24-1.61 | NSD | NSD | NSD | -8 studies analysed for IVR; 4 for CSS and MFS; 2 for OS |
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Systematic reviews reporting IVR in patients undergoing dURS and RNU versus RNU alone.
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| Study | Modality | Pt, n | Metric | Sens,% | Spec, % | PPV, % | NPV, % | Brief summary of findings | | Wada et al., 2021 [72] | PDD | 20 | Per biopsy; per patient | 62.5a; 86.7b | 67.3a; 66.7b | 59.5a; 85.7b | 70a; 25b | PDD was not found to be significantly more sensitive than WL though it may be better at identifying CIS | | Yoshida et al., 2020 [89] | PDD | 20 | Per biopsy | 93.8 | 77.4 | 81.1 | 92.3 | PDD was found to be significantly more sensitive: PDD 93.8% vs. WL 62.5%, p=0.0025 | | Fukuhara et al., 2020 [90] | PDD | 10 | Per biopsy | 100 | 50 | 52.4 | 100 | PDD was found to be significantly more sensitive: PDD 100% vs. WL 38.4%, p=0.004, | | Kata et al., 2016 [74] | PDD | 54c | Per biopsy | 95.8 | 96.6 | - | - | PDD was found to be significantly more sensitive in detecting UUT-UC: PDD 95.8% vs. WL 53.5%, p<0.0001; for CIS: PDD 93.8% vs. WL 18.8%, p=0.0006 | | Aboumarzouk et al., 2013 [91] | PDD | 30 | Per patient | 94 | 100 | 100 | 92.9 | PDD was not found to be significantly more sensitive than WL | | Ahmad et al., 2012 [92] | PDD | 26 | Per biopsy | - | - | - | - | 10 lesions within this study were only visible when using PDD | | Aboumarzouk et al., 2012 [93] | PDD | 32 | Per biopsy | 96 | 100 | 100 | 88 | PDD was not found to be significantly more sensitive than WL | | Somani et al., 2010 [94] | PDD | 4 | - | - | - | - | - | Pilot study found that PDD is safe and feasible | | Iordache et al., 2018 [80] | NBI | 62 | Per patient | - | - | - | - | Overall detection was significantly better with NBI: NBI 98.4% vs. WL 91.9% (p<0.05) | | Traxer et al., 2011 [95] | NBI | 27 | Per biopsy | - | - | - | - | 22.7% improved detection with NBI over WL reported | | Freund et al., 2019 [81] | CLE | 36 | Biopsy grading | 77 | 63 | 79 | 60 | Reported 90% sensitivity and 86% specificity when non-diagnostic cases excluded | | Breda et al., 2018 [84] | CLE | 14 | Biopsy grading | - | - | - | - | A high concordance was found between CLE findings and histology results | | Villa et al., 2016 [82] | CLE | 14 | - | - | - | - | - | Pilot study found that CLE is safe and feasible | | Bui et al., 2015 [83] | CLE | 11 | - | - | - | - | - | Pilot study found that CLE is safe and feasible | | Bus et al., 2016 [85] | OCT | 26 | Biopsy grading; biopsy staging | 87d; 100e | 90d; 92e | 93d; 92e | 82d; 100e | A high grade and stage concordance was found when compared with surgical specimens | | Bus et al., 2013 [86] | OCT | 8 | | | | | | Pilot study found that OCT is safe and feasible | | Farnum et al., 2018 [87] | ELUS | 27 | Patient staging (<pT2 and ≥pT2) | 76.2f; 16.7g | 16.7f; 76.2g | 76.2f; 16.7g | 16.7f; 76.2g | Figures shown were reported for ELUS tumour staging; understaging: 22.2%; overstaging: 25.9% of cases | | Matin et al., 2010 [88] | ELUS | 15 | Biopsy staging | 100 | 80 | 66.7 | 100 | Figures shown were reported for ELUS tumour staging |
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Summary of studies reporting novel technologies to improve dURS.
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