ESOU18: New Diagnostic Tools for Upper Urinary Tract TCC

Amsterdam, The Netherlands (UroToday.com) The management of upper tract urinary cancer (UTUC) has dramatically changed over the last two decades, thanks to technological advances and the better understanding of its biological process. Kidney Sparing Surgery (KSS), including the endourological approach and distal ureterectomy, were traditionally reserved for patients with contraindications to radical nephro-ureterectomy (RNU), such as patients with a solitary kidney, bilateral tumors, and chronic kidney disease [1]. Recently, the European Association of Urology (EAU) Guidelines [2] on UTUC has recommended conservative management of low risk tumors, including:

  • Patients with solitary lesions <2 cm, 
  • Low grade tumors and
  • Non-muscle invasive infiltrative lesions at CT scan and 
  • With absence of upper urinary tract dilatation. 
Therefore, the accurate staging and grading of UTUC lesions is mandatory for the appropriate treatment decision. 

Currently, ureteroscopic evaluation with biopsy and cytology are considered mandatory for the diagnosis of UTUC. Unfortunately, conventional ureteroscopy is not able to provide real-time information on stage and grade, and many difficulties exist in detecting small sized flat lesions suggestive for carcinoma in situ (CIS). Furthermore, ureteroscopic biopsy of upper urinary tract lesions entails a substantial risk of understaging and/or undergrading due to lack of sufficient tissue for analysis.

According to the literature, up to 25% of UTUC biopsies are non-diagnostic because of the insufficient tissue in the specimen [3]. Moreover, a recent biopsy series published by Smith et al. in 2011 showed that 43% of patients were upgraded and/or upstaged (non-muscle invasive to muscle invasive disease) on the final RNU histopathology, when compared to the biopsy findings [4]. 

To improve the visualization of UTUC, new endoscopic imaging techniques have been developed, including the Storz professional imaging enhancement system (IMAGE 1S) and narrow band imaging (NBI). IMAGE 1S includes different modalities in an attempt to enhance the sharpness of the displayed image, and to obtain clearer visibility of darker areas within the image. NBI improves tumor detection using special filters. In essence, through NBI the light spectrum is reduced to its blue (415 nm) and green (540 nm) components, which are well absorbed by hemoglobin. This results in enhanced contrast between the mucosa and blood vessels, leading to the well-vascularized UTUC lesions to be better seen. NBI has been shown to detect approximately 15% more tumors when compared to standard white light ureteroscopy. [5]

Another development is the microscopic imaging technique, including confocal laser endomicroscospy (CLE, CellvizioTM) and optical coherence tomography (OCT). Generally speaking, these technologies makes it possible to obtain real-time data on tissue differentiation, and thus distinguish between low and high grade lesions. The confocal laser endomicroscospy (CLE, CellvizioTM) is a new device that has been developed for a better cytological characterization of both bladder cancer and UTUC [6][7]. CLE has been shown to be useful for grading evaluation. The system consists of a low-power laser light which reacts to fluorescein, a topical fluorescent dye, so that resolution of cellular architecture and surrounding blood vessels can be augmented. The dye is injected locally (bladder or renal pelvis/ureter); which the probe, according to predefined criteria, enables a dynamic microscopic characterization of bladder or UTUC lesions. Recently, the authors had found a concordance rate of 100% and 83% in successfully characterized low and high risk UTUC, when correlated to final histopathology of the specimen. [8] 

The OCT techniques provides real time high quality cross sectional images of superficial tissue.

Similarly to the ultrasonography, OCT utilizes the signal created by waves reflected from various

surrounding tissue surface. Through the usage of near infrared light spectrum (890 -1300 nm), it enables tissue imaging at 10-20 mm resolution and up to 2 mm in depth. OCT differentiates between abnormal and normal tissue, showing the tissue infiltration status. Recently, a study demonstrated 83% concordance between the intraoperative OCT evaluation and the final histopathology [9]. The OCT sensitivity and specificity for tumor invasion were 100% and 92%, respectively.

Despite the experimental nature of these novel technologies, these recent advances offer the opportunity to improve UTUC detection and assessment.  By improving diagnostic accuracy, this will potentially allow for the use of specially “tailored therapies” for UTUC patients.


Speaker: Alberto. Breda, MDChief of the Uro-Oncology Division and of the Kidney Transplant Unit and at Fundacio Puigvert,  Barcelona, Spain

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at The 15th Meeting of the EAU Section of Oncological Urology ESOU18 - January 26-28, 2018 - Amsterdam, The Netherlands

References

1. P. Smith, J. Mandel, and J. D. Raman, “Conservative nephron-sparing treatment of uppertract tumors.,” Curr. Urol. Rep., vol. 14, no. 2, pp. 102–8, Apr. 2013.tumors.,” Curr. Urol. Rep., vol. 14, no. 2, pp. 102–8, Apr. 2013.

2. M. Rouprêt et al., “European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2017 Update,” Eur. Urol., Sep. 2017.

3.  F. Tavora et al., “Small endoscopic biopsies of the ureter and renal pelvis: pathologic pitfalls.,” Am. J. Surg. Pathol., vol. 33, no. 10, pp. 1540–6, Oct. 2009.

4. A. K. Smith et al., “Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management.,” Urology, vol. 78, no. 1, pp. 82–6, Jul. 2011.

5.  O. Traxer, B. Geavlete, S. G. diez de Medina, M. Sibony, and S. M. Al-Qahtani, “Narrow-band Imaging Digital Flexible Ureteroscopy in Detection of Upper Urinary Tract Transitional-Cell Carcinoma: Initial Experience,” J. Endourol., vol. 25, no. 1, pp. 19–23, Jan. 2011.

6. S. P. Chen and J. C. Liao, “Confocal laser endomicroscopy of bladder and upper tract urothelial carcinoma: a new era of optical diagnosis?,” Curr. Urol. Rep., vol. 15, no. 9, p. 437, Sep. 2014.urothelial carcinoma: a new era of optical diagnosis?,” Curr. Urol. Rep., vol. 15, no. 9, p. 437, Sep. 2014.

7. L. Villa, J. Cloutier, J.-F. Cotè, A. Salonia, F. Montorsi, and O. Traxer, “Confocal Laser Endomicroscopy in the Management of Endoscopically Treated Upper Urinary Tract Transitional Cell Carcinoma: Preliminary Data.,” J. Endourol., vol. 30, no. 2, pp. 237–42, Feb. 2016.

8.  A. Breda et al., “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,” Eur. Urol. Focus, Jun. 2017.

9. M. T. J. Bus et al., “Optical Coherence Tomography as a Tool for In Vivo Staging and Grading of Upper Urinary Tract Urothelial Carcinoma: A Study of Diagnostic Accuracy,” J. Urol., vol. 196, no. 6, pp. 1749–1755, Dec. 2016.
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