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
- Department of Pathology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Department of Urology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
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