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The Diagnostic Yield and Concordance of Ureterorenoscopic Biopsies for Grading of Upper Tract Urothelial Carcinoma: A Dutch Nationwide Analysis - Beyond the Abstract

During the last decade, ureterorenoscopic laser ablative treatment of upper tract urothelial carcinoma (UTUC) has gained great popularity. This development is unsurprising in light of the renal sparing character of the ureteroscopic treatment with a similar oncologic outcome in low-grade and non-invasive UTUC as radical nephroureterectomy.1 Yet, accurate patient selection is required to warrant good oncologic results. To aid patient selection, a risk-stratification has been implemented in international guidelines.2-4 This risk-stratification relies on the tumor stage, the cytologic grade, or the histopathologic grade. As such, if radiologic imaging and cytology do not provide diagnostic certainty, ureterorenoscopic biopsies are essential to the diagnostic approach. However, with regard to the limited diagnostic yield and the high rate of upgrading of ureterorenoscopic biopsies,5-8 the current approach towards patient selection might lead to suboptimal oncologic outcomes. To our knowledge, large, nationwide studies to evaluate the above-mentioned diagnostic limitations were lacking.


As a result, we present the first nationwide study in which the findings of ureterorenoscopic biopsies of UTUC are compared with the histopathology of subsequent surgical resections. The study is based on excerpts of the nationwide Dutch Pathology Registry (PALGA) from 2011 until 2018. Besides the diagnostic yield and the diagnostic accuracy of histologic grading, the present study also addressed the diagnostic accuracy of biopsy-based grading to predict the stage in the final surgical resection specimen.

In total, 1002 UTUC-positive renal units were included, of which 776 UTUC-positive renal units were graded according to the World Health Organization (WHO) 2004 classification in either the ureterorenoscopic biopsy, the localization-matched surgical resection or in both. In our study, the diagnostic yield of ureterorenoscopic biopsies for a classifying diagnosis was 89%. In the case of UTUC, the diagnostic yield for biopsy-based grading was 97% of the biopsies. The concordance of high-grade biopsies with regard to the final histopathology was 97% with downgrading in 2% of the cases. The concordance of low-grade biopsies, however, was only 62% with upgrading in 33% of the cases.

Histopathologic staging was only reported in 72% of the UTUC-positive biopsies. Yet, high-grade biopsies resulted in a positive predictive value (PPV) of 81% to predict invasive growth in the resection specimen (≥T1). The PPV of biopsy high-grade UTUC to predict final muscle invasion (≥T2), nonetheless, was 66%.

In conclusion, the findings of this first nationwide study re-affirm the slightly suboptimal diagnostic yield of ureterorenoscopic biopsies for a classifying diagnosis. Yet, the diagnostic yield for UTUC grading is high. The most important limitation is the high rate of upgrading. One-third of low-grade biopsies are upgraded with regard to the final histopathology. It is likely that this limitation arises from diagnostic error and sampling error (insufficient material, crush artifacts). Tumor grade heterogeneity and disease progression may also contribute to the low concordance of the histopathologic grade.

From a critical point of view, the high rate of upgrading might imply that one-third of patients, who qualify for kidney-sparing treatment according to one of the criteria recommended for risk-stratification, are stratified incorrectly. Due to the lack of clinical follow-up data, the clinical impact of upgrading was unfortunately not evaluated in the present study. These worrisome findings highlight, whatsoever, the importance of a timely and stringent ureterorenoscopic follow-up following kidney sparing surgery. Moreover, it stresses the need for improvements in the diagnostic approach to optimize the risk-stratification to warrant good oncologic outcomes.

Written by: Jan Erik Freund, MD, (Twitter: @JEFreund),1 Jaap Legemate, MD, PhD, (Twitter: @LegemateJaap),2 and Theo M de Reijke, MD, PhD, FEBU2

  1. Department of Pathology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
  2. Department of Urology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
References: 

  1. Seisen, Thomas, Benoit Peyronnet, Jose Luis Dominguez-Escrig, Harman M. Bruins, Cathy Yuhong Yuan, Marko Babjuk, Andreas Boehle 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." European urology 70, no. 6 (2016): 1052-1068.
  2. Rouprêt, Morgan, Pierre Colin, and David R. Yates. "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." (2014): 181-183.
  3. Rouprêt M, Babjuk M, Burger M, Compérat E, Cowan NC, Gontero P, et al. EAU Guidelines on Upper Urinary Tract Urothelial Carcinoma. In: EAU Guidelines Edn presented at the EAU Annual Congress Amsterdam. 2020.
  4. Wang MO, Vorwald CE, Dreher ML, Mott EJ, Cinar A, Mehdizadeh H, et al. "Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: Treatment of low-risk upper tract urothelial carcinoma." (2016): 27(1):138–44.
  5. Tavora, Fabio, Daniel A. Fajardo, Thomas K. Lee, Tamara Lotan, Jeremy S. Miller, Hiroshi Miyamoto, and Jonathan I. Epstein. "Small endoscopic biopsies of the ureter and renal pelvis: pathologic pitfalls." The American journal of surgical pathology 33, no. 10 (2009): 1540-1546.
  6. Wang, Jeffrey K., Matthew K. Tollefson, Amy E. Krambeck, Landon W. Trost, and R. Houston Thompson. "High rate of pathologic upgrading at nephroureterectomy for upper tract urothelial carcinoma." Urology 79, no. 3 (2012): 615-619.
  7. Smith, Armine K., Andrew J. Stephenson, Brian R. Lane, Benjamin T. Larson, Anil A. Thomas, Michael C. Gong, J. Stephen Jones, Steven C. Campbell, and Donna E. Hansel. "Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management." Urology 78, no. 1 (2011): 82-86.
  8. Margolin, Ezra J., Justin T. Matulay, Gen Li, Xiaosong Meng, Brian Chao, Varun Vijay, Hayley Silver et al. "Discordance between ureteroscopic biopsy and final pathology for upper tract urothelial carcinoma." The Journal of urology 199, no. 6 (2018): 1440-1445.
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