ESOU 2019: Conservative Management of Upper Tract Urinary Cancer

Prague, Czech Republic (UroToday.com) In this presentation on the conservative management of upper tract urothelial carcinoma (UTUC), Dr. Alberto Breda provides an overview of the current status of conservative treatment options and potential future management options.

UTUC remains a challenge to manage due to the relative rarity of the disease, the difficulties with tissue acquisition and imaging, and difficulties with reliable staging. UTUC accounts for 5-10% of all urothelial carcinoma. Current evaluation with CT urogram lacks adequate staging information (<30% accuracy), provides no information on grade, but does have a >90% detection rate.

Flexible URS (ureteroscopy) allows visualization of 95% of the upper tract. FURS allows for visualization, diagnosis, endoscopic ablation, and treatment of UTUC. It is invaluable in patients with indications for kidney-sparing surgery. He did note that from 2015 to 2018, the EAU guidelines were updated and expanded the eligibility of UTUC lesions up to 2 cm (previously 1 cm) for endoscopic management. Despite the improvement in FURS and the use of additional imaging modalities (narrow band imaging, CLARA, etc), a key problem remains the ability to biopsy these lesions.

I particularly liked this slide, taken from his paper1, which highlights the difficulty with tissue acquisition with the tools we currently have available:
UroToday ESOU19 quality of histological example

This where some novel new technologies may help bridge the gap and provide real-time data regarding grade and stage. Especially, as we are often treating these lesions in the same setting as the initial diagnosis – often without histology or staging information.
  1. Confocal laser endomicroscopy (CLE) aka CellVizio – allows high-resolution microscopy of tissue resulting in images of the cellular structure, high-grade concordance with final pathology.
- Dr. Brada has been closely involved with the development of this technology.
- Dr. Brausi gave a talk on this technology earlier at this conference 
- In an update to their initial published experience with 10 patients2, Dr. Breda notes that with 26 patients, there has been a 75% and 85% concordance with high and low-grade pathology, respectively – less than their original experience, but still pretty good!
- This may help better select patients for conservative vs. radical treatment

  1. Optical Coherence Tomography (OCT) – cross-sectional high-resolution images. Provides information regarding tumor grade and stage.
He then shifted gears to lower tract recurrences following UTUC diagnostics and treatments – retrograde intrarenal surgery (RIRS). Indeed, a systematic review by Marchioni et al. (BJU 2017) demonstrated that, from 7 studies, patients undergoing diagnostic URS prior to nephroureterectomy had a higher rate of bladder recurrences (HR 1.56, p < 0.001).3 Yet, despite the growing concern, there are already guidelines in the EAU for this scenario – and they recommend antegrade instillation of BCG or MMC in the upper tract following UTUC endoscopic treatment. Unfortunately, very few people adhere to this.

In a prospective, non-randomized trial at his institution (unpublished data, to be presented at EAU 2019), they treated 48 patients – 24 controls and 24 patients treated with single-dose adjuvant mitomycin within 6 hours of UTUC treatment (via retrograde access). The primary outcome was safety, but a secondary outcome was oncologic outcomes. They found that single dose MMC was associated with a significantly lower lower-tract recurrence rate compared to control. They are continuing this in a prospective manner. Hopefully, additional results will help solidify this recommendation in the guidelines.

Lastly, he tackled the surveillance issues in the endoscopic management of UTUC. Specifically, it involves significant repeat imaging (CT Urograms) and repeat endoscopic evaluation with ureteroscopy. Second look URS is the strongest predictor of recurrence and progression. However, this paradigm may change – just as in bladder cancer, there is a strong interest in numerous urine biomarkers that may help replace repeat URS. These include CellDetect®, AnticipateX, Cxbladder™, mRNA tests, and EpiCheck™.

He briefly reviewed his institution’s experience with evaluating EpiCheck in the UTUC population4. They prospectively assessed voided urine samples of patients who had URS for radiologic diagnosis of UTUC since 6/2018. Results were then compared to pathology from 3 forceps biopsies. The breakdown of their pilot study is below:
UroToday ESOU19 results of pilot study
While the PPV was high, the NPV was just 50%. They are naturally moving to a prospective study to open soon.

There are lots of developments in the conservative management of UTUC that may alter the treatment paradigm. 

 
Presented by: Alberto Breda, MD, Department of Urology, Fundació Puigvert, Barcelona, Spain

Written by: Thenappan Chandrasekar, MD. Clinical Instructor, Thomas Jefferson University, Twitter: @tchandra_uromd, @TjuUrology, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic

References: 
1. Breda et al. WJU 2018
2. Breda et al. (2017) Correlation Between Confocal Laser Endomicroscopy (Cellvizio®) and Histological Grading of Upper Tract Urothelial Carcinoma: A Step Forward for a Better Selection of Patients Suitable for Conservative Management, European Urology Focus, 4 (6), 954–959. 
3. Marchioni et al. (2017) Impact of diagnostic ureteroscopy on intravesical recurrence in patients undergoing radical nephroureterectomy for upper tract urothelial cancer: a systematic review and meta‐analysis. BJU, 120 (3), 313-319.
4. Breda et al. WJU 2019
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