Editing Upper Urinary Tract Urothelial Cancer (section)

=== <span style="color:#ff0000">Other ===

==== <span style="color:#ff0000">Cystoscopy</span> ====
*'''<span style="color:#ff0000">Mandatory because upper urinary tract tumors are often associated with bladder cancers</span>'''

==== <span style="color:#ff0000">Upper tract endoscopy +/- biopsy of any identified lesion</span> ====
*'''<span style="color:#ff0000">Diagnostic ureteroscopy</span>'''
**'''Indications for ureteroscopy or percutaneous endoscopy of the upper urinary tract (and when diagnostic and prognostic details are needed)[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
**#'''Lateralizing hematuria'''
**#'''Suspicious selective cytology''' 
**#'''Radiographic presence of a mass or urothelial thickening'''
[[File:Cystoscopy - Uretereal Cancer.jpg|center|frame|Ureteral tumour on endoscopy[[commons:File:Cystoscopy_-_Uretereal_Cancer.jpg|Source]]]]
** '''URS allows direct visualization of the tumor and biopsy of suspected areas'''
*** '''<span style="color:#ff0000">Document key descriptive features of UTUC that may guide further diagnostic testing and inform therapeutic interventions as well as provide points of comparison for subsequent ureteroscopic surveillance including:[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
***#'''<span style="color:#ff0000">Location (ureteral segment, renal pelvis, calyceal sites and lower tract)'''
***#'''<span style="color:#ff0000">Size'''
***#'''<span style="color:#ff0000">Number'''
***#'''<span style="color:#ff0000">Focality'''
***# '''<span style="color:#ff0000">Appearance (sessile, papillary, flat/villous)'''
***#'''<span style="color:#ff0000">Quality of visualization </span>'''
***#*Can impact the accuracy of endoscopic inspection (e.g., bleeding, difficulty in access, tumor location, artifacts from instrumentation) and should be documented in endoscopic reports.
***See checklist in [https://www.auanet.org/guidelines-and-quality/guidelines/non-metastatic-upper-tract-urothelial-carcinoma Guidelines Statement 2,Table 3: Standardized Upper Tract Endoscopy Suggested Reporting Elements]
***The urologist’s impression of the tumor grade based on ureteroscopic appearance is likely to be correct in only 70% of cases, suggesting that biopsy is also needed to further define this important aspect of staging
****'''<span style="color:#ff0000">Biopsy of any identified lesion</span>'''
*****'''Approaches (2):'''
******'''Ureteroscopic biopsy with forceps'''
******'''Fluoroscopically guided retrograde brush biopsy'''
*****'''Mucosal abnormalities may be difficult to biopsy effectively'''
******'''Attempted tissue confirmation may be facilitated with the use of brush biopsies or percutaneous image-guided biopsy.'''
**'''Diagnostic accuracy'''
***'''Preoperative determination of the stage of UTUC tumors remains difficult. <span style="color:#ff0000">Therefore, in predicting the tumor stage, a combination of the radiographic studies, the visualized appearance of the tumor, and the tumor grade provides the surgeon with the best estimation for risk stratification.</span>'''
****'''<span style="color:#ff00ff">Systematic review and meta-analysis evaluating diagnostic accuracy of URS biopsy (2020)</span>'''
***** Included studies comparing URS biopsy to pathology on surgical specimen (radical nephroureterectomy or segmental ureterectomy)
***** Results:
****** Included 23 studies comprising 2232 patients
****** Moderate to high risk of bias accross studies
****** Stage-to-stage match
******* Positive predictive value for cT1+/muscle-invasive: 94%
******* Negative predictive value for cTa-Tis/non-muscle-invasive disease of 60%
****** Grade-to-grade match
******* High-grade (cHG/pHG): 97%
******* Low-grade (cLG/pLG): 66%
****** Grade-to-stage match
******* Positive predictive value for cHG/muscle-invasive disease: 60%
******* Negative predictive value for cLG/non-muscle-invasive disease: 77%
****** '''<span style="color:#ff0000">Overall</span>'''
******* '''<span style="color:#ff0000">32% undergrading</span>'''
******* '''<span style="color:#ff0000">46% understaging</span>'''
******** '''<span style="color:#ff0000">A precise correlation with eventual tumor stage is difficult</span>''' mainly because of technical limitations of use of small biopsy instruments through the narrow channel of the flexible ureteroscope, resulting in the small size and shallow depth of ureteroscopic biopsy specimens. Brush biopsy may be used if cup biopsy forceps fail to obtain adequate tissue.
***** [https://pubmed.ncbi.nlm.nih.gov/32674841/ Subiela, José Daniel, et al.]"Diagnostic accuracy of ureteroscopic biopsy in predicting stage and grade at final pathology in upper tract urothelial carcinoma: Systematic review and meta-analysis." ''European Journal of Surgical Oncology'' (2020).
***'''<span style="color:#ff0000">Reasonable histologic correlation</span>''' (78-92%)
** '''In general, CIS of the upper tract is a presumptive diagnosis that is made by the presence of unequivocally positive selective cytology in the absence of any radiographic or endoscopic findings'''
**'''Rare situations where endoscopic upper tract evaluation may not be necessary (2)[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
**#'''Findings would not influence decision-making, such as patients with severe co-morbidities who are ineligible for intervention or request expectant management.'''
**#'''Other diagnostic means clearly confirm the diagnosis of UTUC and thus histologic tissue confirmation is not clinically required.'''
**#*Example would include high-grade (HG) selective cytology or other source of tissue diagnosis, and clear and convincing radiographic findings of upper tract urothelial-based tumor(s) such as an obvious enhancing, urothelial based soft-tissue filling defect on contrast-enhanced imaging with urography.
**#**Such situations may be particularly relevant in patients with a history of HG urothelial cancer.
**'''If concomitant lower tract tumors (bladder/urethra) are discovered at the time of ureteroscopy, the lower tract tumors should be managed in the same setting as ureteroscopy.[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
***Consensus on prioritization of procedure sequencing (managing bladder before or after same-setting ureteroscopy) is lacking and heavily scenario-dependent.
****Rationale for managing the bladder first:
*****Optimizing visualization within the bladder
*****Avoiding back-pressure or back-washing into the upper tract in the case of post-ureteroscopy stenting
*****Permitting final confirmation of bladder hemostasis.
****Addressing the upper tract first may be preferred in cases of
*****Bulky bladder tumor involvement where complete resection is not possible
*****Bulky upper tract disease in which risk assessment is the priority.
***Some advocate use of ureteral access sheaths to reduce risk of seeding of tumors from bladder to upper tract or from upper tract to the lower tract
****The benefits of this approach require further prospective study.
** '''In cases of existing ureteral strictures or difficult access to the upper tract, minimize risk of ureteral injury by using gentle dilation techniques such as temporary stenting (pre-stenting) and limit use of aggressive dilation access techniques such as ureteral access sheaths.[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
***Perforation or disruption of the urothelium in patients with UTUC can risk tumor seeding outside the urinary tract.
****Recognized perforation or injury events should be documented with immediate cessation of the procedure as soon as safely possible with additional steps to limit sequelae (e.g., stenting, bladder decompression with urethral catheter drainage to limit reflux, nephrostomy tube placement in cases of a completely obstructive ureteral tumor and evidence of contrast extravasation).
***Precautionary measures in cases of difficult ureteral access such as avoiding dilation or placing a stent without performing ureteroscopy and then returning one-two weeks later to repeat the procedure (pre-stenting) can decrease the risk of iatrogenic injury and provide opportunity for a safer and more successful procedure.
**'''In cases where ureteroscopy cannot be safely performed or is not possible, an attempt at selective upper tract washing or barbotage for cytology may be made and pyeloureterography performed in cases where good quality imaging such as CT or MR urography cannot be obtained.[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
***When endoscopic examination of the involved upper tract is not possible, findings from selective cytology and retrograde pyelography may provide useful, objective and sufficient information for risk stratification .
****Example scenarios may include washings taken at the time of percutaneous nephrostomy tube placement or during attempted retrograde ureteroscopy that is abandoned for safety concerns.
**'''At the time of ureteroscopy for suspected UTUC, ureteroscopic inspection of a radiographically and clinically normal contralateral upper tract should not be performed.[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
***Endoscopic procedures have risks for patient injury and the potential for tumor seeding in the presence of urothelial cancer. Performing upper tract endoscopy in the setting of a completely normal contralateral upper urinary tract without clinical indication or as a “screening” procedure is unnecessary, placing patients at undue risk and should not be performed
**'''Technique: Endoscopic Evaluation and Collection of Urine Cytology Specimen'''
***Summary of Steps
**** Cystoscopy is performed and the bladder inspected for concomitant bladder disease.
**** The ureteral orifice is identified and inspected for lateralizing hematuria.
**** A small-diameter (6.9 or 7.5 Fr) ureteroscope is passed directly into the ureteral orifice, and the distal ureter is inspected before any trauma from a previously placed guidewire or dilation.
**** A guidewire is then placed through the ureteroscope and up the ureter to the level of the renal pelvis under fluoroscopic guidance.
**** The flexible ureteroscope is used to visualize the remaining urothelium.
**** When a lesion or suspicious area is seen, a normal saline washing of the area is performed before biopsy or intervention. If the ureter does not accept the smaller ureteroscope, active dilation of the ureter is necessary.
**** Special circumstances include prior urinary diversion and tumor confined to the intramural ureter. With cases of prior urinary diversion, identification of the ureteroenteric anastomosis is difficult and may require antegrade percutaneous passage of a guidewire down the ureter before endoscopy. The wire can be retrieved from the diversion, and the ureteroscope can be passed in a retrograde fashion. The nephrostomy tract does not need to be fully dilated in this setting
*'''Antegrade endoscopy'''
** '''Percutaneous access to the renal pelvis may be required for diagnosis or treatment.''' In such cases, antegrade urography and ureteroscopy may be useful for tumor resection, biopsy, or simple visualization.
*** '''Tumor cell implantation in the retroperitoneum and along the nephrostomy tube tract has been reported after these procedures'''

==== <span style="color:#ff0000">Universal histologic testing of UTUC with additional studies, such as immunohistochemical (IHC) or microsatellite instability (MSI)</span> ====
*'''Routine tissue testing provides a more sensitive, first-line means to identify Lynch syndrome-associated features in tumor samples[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
**Immunohistochemical testing
*** Can preliminarily identify the altered proteins associated with Lynch syndrome, and thus help to identify patients who may have the syndrome, who then require confirmation with further genetic (germline) testing
***Widely available
**Microsatellite instability
***Identifying the presence of Lynch syndrome-associated and MSI-high cancers also has clinical implications related to therapeutic treatment options, including identified sensitivity of urothelial cancers with mutations in DNA damage repair genes to systemic agents such as immune checkpoint inhibitors and cisplatinum-based chemotherapy

==== <span style="color:#ff0000">Percutaneous biopsy</span> ====

* Safe and effective technique[https://pubmed.ncbi.nlm.nih.gov/24905868/ §]
*Consider for upper tract urothelial lesions which are not amenable to endoscopic biopsy[https://pubmed.ncbi.nlm.nih.gov/24905868/ §]
*'''Systematic review of 288 patients undergoing percutaneous nephroscopic resection of tumour found a tract seeding rate of 0.3%[https://pubmed.ncbi.nlm.nih.gov/22471401/]'''

==== Urine fluorescence in situ hybridization (FISH) ====
*May be considered adjunctively to adjudicate atypical or suspicious cytology results.

==== Retrograde pyelograms ====
*Provide a roadmap for evaluation and possibly planning kidney-preserving strategies
*Should be considered at initial evaluation with images retained in the patient record