Vol.:(0123456789) 1 3 World Journal of Urology https://doi.org/10.1007/s00345-019-02813-8 ORIGINAL ARTICLE Tumour architecture, grade and location remain predictors of non‑organ‑confned upper tract urothelial carcinoma at time of radical nephroureterectomy: results from a multicenter Norwegian external validation study Bjarte Almås 1  · Stein Øverby 2  · Ole J. Halvorsen 3,4  · Lars A. R. Reisæter 5  · Jørg Assmus 7  · Birgitte Carlsen 6  · Anders Loe 1  · Christian Beisland 1,3 Received: 18 March 2019 / Accepted: 17 May 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Purpose Selecting patients for intensifed treatment for upper tract urothelial carcinoma can be challenging, partly due to the lack of accurate preoperative staging tools. Several preoperative staging models for upper tract urothelial carcinoma have been presented, but none have been externally validated. The aim of the current study was to perform an external validation of the Margulis nomogram for predicting non-organ-confned upper tract urothelial carcinoma at time of nephroureterectomy. Methods 209 patients from two high-volume centres in Norway were treated with radical nephroureterectomy during the period 2005–2017. 163 patients with complete data necessary for external validation of the Margulis nomogram were included in the study. All relevant covariates were analysed with uni- and multivariate regression analysis to assess their ability to predict non-organ-confned disease. The Margulis nomogram was applied on the present cohort to calculate pre- dicted risk of non-organ-confned disease. This was compared to the observed risk to assess model calibration. The Margulis nomogram accuracy was measured as the area under the curve in a receiver operator characteristics curve to evaluate model discrimination. Results Tumour grade (OR 28.1, p = 0.001) and architecture (OR 4.72, p < 0.001) were independent predictors of non-organ- confned disease. There was a high concordance between predicted and observed risk quantifed with a Cronbach alpha of 0.96. The Margulis nomogram had an area under the curve of 0.83 in predicting non-organ-confned disease when applied on the current cohort. Conclusions We consider the Margulis nomogram validated for clinical use. Keywords Diagnostic model · Upper tract urothelial carcinoma · External validation Introduction Urothelial carcinoma in the upper urinary tract (UTUC) constitutes 5–10% of all urothelial carcinomas [1]. UTUC is an aggressive disease, at diagnosis a higher proportion of the tumours are muscle-invasive and high-grade than urothelial cancer of the bladder [2]. The standard treatment for high-grade or invasive UTUC is a radical nephroure- terectomy (RNU) with complete excision of the ipsilateral bladder cuf. Kidney-sparing approaches such as endoscopic treatment or ureter resection can be considered for selected cases of low-grade disease [3]. About 40% of the tumours are non-organ-confned at time of RNU, and the 5-year cancer-specifc survival (CSS) in these cases is below 50% [4, 5]. Due to the high mortality of the disease, intensifed treat- ment including lymph node dissection (LND) and chemo- therapy as neo-adjuvant or adjuvant treatment have been suggested for high-risk patients. The efcacy of adjuvant chemotherapy after RNU in this setting has been demon- strated in recent publications [6–8], and is currently accepted Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00345-019-02813-8) contains supplementary material, which is available to authorized users. * Bjarte Almås Bjarte.Almas@helse-bergen.no Extended author information available on the last page of the article