EAU 2019: Troubleshooting Challenges in Diagnostics

Barcelona, Spain (UroToday.com) In this first session on upper tract urothelial carcinoma (UTUC), Dr. Peter Black provided an overview of the diagnostics of UTUC and the difficulties often faced by physicians. The talk kicked off the UTUC session.

Ultimately, the tissue is the main issue in UTUC, and the bulk of this talk focused on how to get it and when.

The 3 main diagnostic challenges are:

1. Whether to biopsy?
2. How to biopsy?
3. Risk stratification – identifying patients best suited for endoscopic management, radical nephroureterectomy (RNU) and/or (neoadjuvant) chemotherapy

The current EAU guidelines flowchart for UTUC diagnosis is as follows:


  • All patients require a CT Urogram, urine cytology and cystoscopy (all Class A recommendations)
  • +/- flexible ureteroscopy with biopsies – Class C recommendation, only if it will change management

Three main options for imaging the upper tract:

  1. CT Urogram – due to speed, efficacy, and cost, it remains the gold standard
    1. Generally, sensitivity >70% and specificity > 93%
    2. But, there are limits to sensitivity: (Wang et al. JUrol 2010)
      1. Sensitivity drops with size – 96% for masses 5-10 mm, but 40% for masses < 3 mm
      2. Flat lesions are even more challenging
  2. Magnetic resonance (MR) Urogram
    1. Reserved for patients who cannot (or prefer not to) have CT Urogram
    2. Still has a risk of NSD with low eGFR
  3. Retrograde pyelogram
    1. Reserved for patients with eGFR <30; must be done with a non-contrast CT to evaluate renal parenchyma
Knowing the limitations of these tools, what is required to treat? Imaging alone? Imaging + cytology? Imaging + cytology + tissue biopsy?

  • In a Korean series (Hong et al. J Soc Lap Surg 2010) of 244 NUx done with imaging and cytology alone, 2.9% of the final specimens were benign
  • Next, he noted that visual evaluation of the tumor via URS isn’t sufficient or perfect: in a paper by El Hakim et al. (Urology 2004), 8/28 tumors thought to be LG was actually HG, and the 2 lesions thought to be benign were actually tumor (1 LG and 1 HG)
He summarizes the key issues with URS+biopsy in the slide below:


How good is ureteroscopic biopsy?

  • It has an 80-90% concordance with NUx grade – except in LG biopsies (40% concordance) – therefore, it tends to get upgraded relatively often
  • Has little utility for tumor staging
Does URS before NUx cause cancer dissemination?

  • A meta-analysis (Guo et al. BJUI 2018) demonstrated no difference in OS, RFS or MFS; they did show a slight benefit with URS in terms of CSS likely related to selection.
    • However, they did note clear evidence that it increases the risk of intravesical bladder recurrence (IVR) – HR 1.51 (95%CI 1.27-1.71)
  • So, based on this, shouldn’t stop doing URS prior to NUx – but may want to consider intravesical therapy after
Urine cytology – he then reviewed some basic data on urine cytology. Still has its utility – especially in the absence of a good biopsy. If grossly positive, it is often pretty accurate.

  • Voided cytology less sensitive for UTUC than for bladder cancer
  • But, selective upper tract cytology has better results
  • 71% sensitivity for HG tumors, 78% for muscle invasive tumors
The situations in which URS and biopsy are “no brainers” are the following:


But for patients with a large upper tract tumor visible on a scan that is too large for endoscopic ablation and patient not eligible for NAC, is biopsy really useful?

He then spent some time on ureteroscopic biopsy techniques, and used some videos to share some practical tips and tricks – I highlight the relevant ones below:

  1. There are novel imaging tools in the works (optical coherence tomography and confocal laser microendoscopy) that may be useful once mainstream
  2. Disappointing initial results of endoluminal ultrasound by Matin et al. (J Endourology 2018) puts this on hold
  3. There are multiple biopsy tools – 3 mm grasper, nitinol baskets, BIGopsy® forceps, laser (to remove tumor en bloc)
    1. More tissue is probably better, but no strong evidence to support this
    2. With the basket, he recommends basketing, then pushing retrograde and then pull it out through sheath – ends up with more tissue
    3. BIGopsy® forceps are nice because they get a lot of tissue – but visualization can be difficult and requires backloading
Lastly, he addressed some issues with staging. The current staging into high and low risk per EAU guidelines is below:


Though, I should note that the new guidelines have increased the size to 2 cm. 

Low risk patients are eligible for endoscopic treatment, while high risk patients are usually recommended for NUx (or distal ureterectomy).

Unfortunately, staging in UTUC has been a significant issue. Tissue biopsy rarely (~66%) of the time even gets lamina propria, so defining muscle invasion is near impossible. Therefore, we rely primarily on grade to guide decision making.

  • CT scan / axial imaging have high PPV but very poor NPV – therefore, they are not useful for masses that are <= pT2. Mainly useful for masses that are pT3-4.
  • Nomograms combining various clinical and pathologic features (such as the one by Margulis et al. (JUrol 2010)) can help increase predictability – but are still not perfect
As such, 1 in 3 patients undergoing RNUx for low grade Ta UTUC is found to have >= pT2 disease

He finished by highlighting his 3 E’s of URS (which he just came up with): Equipment, Expertise, and Exactitude

Presented by: Peter Black, MD, FRCSC, University of British Columbia, Vancouver, British Columbia, Canada

Written by: Thenappan Chandrasekar, MD (Clinical Instructor, Thomas Jefferson University) (twitter: @tchandra_uromd, @JEFFUrology) at the 34th European Association of Urology (EAU 2019) #EAU19, conference in Barcelona, Spain, March 15-19, 2019.