Editing Upper Urinary Tract Urothelial Cancer (section)

== Diagnosis and Evaluation of UTUC ==

=== <span style="color:#ff0000">UrologySchool.com Summary</span> ===

=== AUA ===
*[https://pubmed.ncbi.nlm.nih.gov/37096584/ '''2023 AUA Guidelines on Upper Tract Urothelial Carcinoma''']
**'''<span style="color:#ff0000">History and Physical Exam (1):</span>'''
**#'''<span style="color:#ff0000">Personal and family history</span>'''
**#*'''<span style="color:#ff0000">To identify known hereditary risk factors for familial diseases associated with Lynch Syndrome</span>'''
**'''<span style="color:#ff0000">Labs (2):</span>'''
**# '''<span style="color:#ff0000">Selective ipsilateral upper tract urine cytology</span>'''
**#'''<span style="color:#ff0000">Estimated GFR/Serum Cr</span>'''
**'''<span style="color:#ff0000">Imaging (1):</span>'''
***'''<span style="color:#ff0000">CT urogram</span>'''
***'''Metastatic staging [not discussed in guidelines]'''
**'''<span style="color:#ff0000">Other (3):</span>'''
**# '''<span style="color:#ff0000">Cystoscopy to assess lower urinary tract</span>'''
**#'''<span style="color:#ff0000">Upper tract endoscopy and biopsy</span>'''
**# '''<span style="color:#ff0000">Universal histologic testing of UTUC with additional studies, such as immunohistochemical or microsatellite instability</span>''' 
**'''Optional (2):'''
***'''Urine fluorescence in situ hybridization (FISH)''' 
***'''Retrograde pyelograms''' 

=== History and Physical Exam ===

==== History ====

* <span style="color:#ff0000">'''Signs and Symptoms'''</span>
** '''Most common presenting sign is hematuria'''
** '''Flank pain is the second most common symptom'''.
*** Pain is typically dull and believed to be '''secondary to a gradual onset of obstruction and hydronephrotic distention'''. 
***In some patients, pain can be acute and can mimic renal colic, typically due to the passage of clots that acutely obstruct the collecting system.
** Some patients are asymptomatic at presentation and are diagnosed when an incidental lesion is found on imaging

* <span style="color:#ff0000">'''Personal and family history'''</span>
** <span style="color:#ff0000">'''To identify known hereditary risk factors for familial diseases associated with Lynch Syndrome'''</span>
***'''If positive, referral for genetic counseling should be offered.[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
****Patients with Lynch Syndrome undergo routine screening due to increased life-long risk for developing associated malignancies, often occurring before 50 years of age[https://pubmed.ncbi.nlm.nih.gov/37096584/]
***'''<span style="color:#ff0000">Lynch syndrome</span>'''
****Familial, autosomal-dominant multi-organ cancer syndrome
****'''Accounts ≈7-20% of UTUC cases in the U.S'''
*****Lynch syndrome may increase the possibility of contralateral upper tract involvement, which is an important potential clinical consideration when developing a treatment plan.
****'''See [[Lynch syndrome|Lynch Syndrome Chapter Notes]]'''

=== Labs ===

==== <span style="color:#ff0000">Selective ipsilateral upper tract urine cytology</span> ====
*'''Provides supplemental histologic data to tumor biopsies'''
**'''High-grade cytology in the setting of low-grade biopsy findings indicates the likely presence of higher-risk features (e.g., high-grade tumor) missed on biopsy sampling.'''
*Reported according to 7 categories (Paris System):
*#Non-diagnostic
*#Negative for high-grade urothelial carcinoma
*#Atypical urothelial cells
*#Suspicious for high-grade urothelial carcinoma
*#High-grade urothelial carcinoma
*#Low-grade urothelial neoplasm
*#Other malignancies
*'''<span style="color:#ff0000">Test characteristics[https://pubmed.ncbi.nlm.nih.gov/27151340/]</span>'''
**'''High specificity (≈90% with selective cytology)'''
**'''Low sensitivity (≈50% with selective cytology)'''
***'''Sensitivity of cytology is directly related to tumor grade'''
*'''<span style="color:#ff0000">Specimen collection considerations</span>'''
**'''<span style="color:#ff0000">Causes of false-positive cytology (2):</span>'''
**# '''<span style="color:#ff0000">Contrast agents</span>'''
**#* Exposure of urothelial cells to ionic, high-osmolar contrast agents as in retrograde pyelography may worsen cytologic abnormalities. 
**#**'''<span style="color:#ff0000">Cytology should be collected prior to any contrast use to avoid artifactual cellular changes from contrast solutions</span>'''
**# '''Inflammation from infection or stones'''
**'''<span style="color:#ff0000">Can be obtained as selective vs. voided urinary specimen</span>'''
***'''<span style="color:#ff0000">Selective cytology</span>''' 
****'''<span style="color:#ff0000">Obtained either as barbotage (saline irrigation and aspiration) or by saline irrigation with passive collection (washings)</span>'''
*****'''<span style="color:#ff0000">Collecting selective cytology after tumor biopsy can improve the yield of cells for cytologic analysis.</span>'''
****'''Preferred over a voided urinary specimen''', due to (3)
****#Improve cellular yield
****#Avoid potential contamination in case of concomitant bladder and/or prostatic urethral disease
****#Avoid theoretical dilution of the specimen from a normal contralateral unit
**'''In a patient with an upper tract filling defect and an abnormal voided cytology, must be cautious in determining the site of origin of the malignant cells'''. Ureteral catheterization for collection of urine or washings may provide more accurate cytologic results.

==== <span style="color:#ff0000">Assessment of renal function</span> ====
*Can help with patient counseling, strategizing treatment sequence (operative approach and administration of systemic therapy), and determination of downstream risks of CKD and potential dialysis.
* '''<span style="color:#ff0000">Recommended test: serum creatinine (to calculate an eGFR)'''
**For more refined evaluation, split function testing such as with differential renal scan or CT volumetric studies may be considered.
**The two formulas for monitoring eGFR commonly reported in the contemporary literature at this time are the [https://www.mdcalc.com/calc/76/mdrd-gfr-equation Modification of Diet in Renal Disease] and [https://www.mdcalc.com/calc/3939/ckd-epi-equations-glomerular-filtration-rate-gfr CKD – Epidemiology Collaboration (CKD-EPI)] equations.
*'''<span style="color:#ff0000">UTUC with associated hydronephrosis'''
**'''Implications on assessment of renal function'''
*** Caused by tumor obstruction may falsely under-estimate preoperative renal function and alter decision-making around the use of neoadjuvant chemotherapy (NAC).
*** Atrophy of the contralateral (unaffected) renal unit may lead to over-estimates of postoperative renal function in the setting of NU since the kidney with lower differential function will remain in situ
**'''Renal decompression either by indwelling ureteric stent or a percutaneous nephrostomy tube placed in an uninvolved renal calyx along with oral fluid hydration for 7-14 days before re-checking eGFR will help to establish a more accurate estimation of baseline renal function.'''
***'''<span style="color:#ff0000">Ureteric stenting is the preferred method of drainage'''
****Percutaneous nephrostomy tubes in the setting of UTUC increases risk of tract seeding and has worse quality of life

==== Liver function tests ====
* Liver is a common site of metastasis

=== Imaging ===

==== Primary ====

===== <span style="color:#ff0000">Options[https://pubmed.ncbi.nlm.nih.gov/37096584/ §]</span> =====
*'''<span style="color:#ff0000">Cross-sectional imaging of the upper tract with contrast including delayed images</span>'''
**'''<span style="color:#ff0000">Preferred modality: multiphase computed tomography (CT) scan with excretory phase imaging of the urothelium</span>'''
***'''<span style="color:#ff0000">Pooled sensitivity of 92%</span>'''
***'''<span style="color:#ff0000">Pooled specificity of 95%</span>'''
**'''<span style="color:#ff0000">If contraindications to contrast-enhanced CT such as chronic kidney disease (CKD) (e.g. eGFR <30[https://medicine.yale.edu/diagnosticradiology/patientcare/policies/nephropathy/]) or untreatable allergy to iodinated contrast medium, use magnetic resonance (MR) urography</span>'''
***'''<span style="color:#ff0000">MRI is less sensitive than CT, similar specificity</span>'''
**'''<span style="color:#ff0000">If contraindications to multiphasic CT and MR urography, use retrograde pyelography in conjunction with non-contrast axial imaging (renal ultrasound) to assess the upper urinary tracts.</span>'''

====== <span style="color:#ff0000">CT urography</span> ======
* High sensitivity (100%) and moderate specificity (60%) for upper tract malignant disease
*'''Typical findings suggestive of an upper urinary tract tumor (3):'''
*# '''Radiolucent filling defects'''
*# '''Non-visualization of the collecting system'''
*# '''Obstruction'''
* '''<span style="color:#ff0000">Differential diagnosis of filling defect includes (11): [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766367/]</span>'''
*# '''<span style="color:#ff0000">Tumour (UTUC, renal cell carcinoma, renal lymphoma, fibroepithelial polyp)</span>'''
*# '''<span style="color:#ff0000">Blood clot</span>'''
*# '''<span style="color:#ff0000">Suburothelial hemorrhage</span>'''
*#'''<span style="color:#ff0000">Stones</span>'''; higher HFU than urothelial carcinoma
*# '''<span style="color:#ff0000">Renal papillary necrosos/sloughed papilla</span>'''
*# '''<span style="color:#ff0000">Hypertrophied papilla</span>'''
*#'''<span style="color:#ff0000">Inflammation</span>'''
*#'''<span style="color:#ff0000">Fungus ball</span>'''
*# '''<span style="color:#ff0000">Tuberculosis</span>'''
*#'''<span style="color:#ff0000">Polyureteritis cystics</span>'''
*#'''<span style="color:#ff0000">Retroperitoneal fibrosis</span>'''
* '''Urothelial cancers are enhancing on arterial/early nephrographic phase, dark/filling defect in urographic phase.''' 
*'''Urothelial cancers have more infiltrative features compared to RCC'''
*'''Radiolucent, noncalcified lesions may require additional evaluation by retrograde urography or ureteroscopy, with or without biopsy and cytology'''
* '''<span style="color:#ff0000">Important to evaluate contralateral kidney to assess (2):'''
**'''<span style="color:#ff0000">Possible bilateral disease''' 
**'''<span style="color:#ff0000">Functionality of the contralateral kidney''' 
[[File:Renal parenchymal phase CT of transitional cell carcinoma.jpg|CT urogram demonstrating filling defect in left renal pelvis. [[commons:File:Renal_parenchymal_phase_CT_of_transitional_cell_carcinoma.jpg|Source]]|center|frame]]

===== <span style="color:#ff0000">Metastasis</span> =====
* '''<span style="color:#ff0000">Chest X-Ray</span>'''
* '''Bone scan,''' consider in the presence of bone pain, elevated calcium or elevated alkaline phosphatase
*PET scans[https://pubmed.ncbi.nlm.nih.gov/37096584/]
**Should not be obtained routinely
**May be selectively considered for patients who are at risk for metastatic recurrence and are not able to have contrast enhanced CT and MRI
*Patients with findings suggestive of metastatic UTUC should be evaluated to define the extent of disease and referred to medical oncology for further management[https://pubmed.ncbi.nlm.nih.gov/37096584/]

=== <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

=== Special Scenarios ===

==== Positive Upper Tract Urinary Cytology ====
* '''<span style="color:#ff0000">First, repeat the cytology to confirm the findings</span>'''
** '''Any source of inflammation, such as urinary infection or calculus, may produce a false-positive result'''
** A subsequent cytologic abnormality from the contralateral side during follow-up is not rare in cases of true-positive results from early CIS
* '''<span style="color:#ff0000">Next, radiographic evaluation of the upper tracts, usually with CT urography, and a complete bladder evaluation with cystoscopy</span>'''
** '''<span style="color:#ff0000">If the bladder evaluation was</span>'''
*** '''<span style="color:#ff0000">Positive for bladder tumour, treat the bladder and follow the voided urinary cytologies.</span>'''
**** If cytology remains positive despite a negative bladder evaluation or after successful treatment of the bladder, proceed to evaluating extravesical sites.
*** '''<span style="color:#ff0000">Negative for bladder tumour, evaluate extravesical sites.</span>'''
**** '''Evaluation of extravesical sites should include <span style="color:#ff0000">selective cytologies from each upper urinary tract,</span>''' ensuring non-contamination of the specimen from the bladder or urethra, '''as well as resection of a representative <span style="color:#ff0000">specimen of the prostatic urethra in men</span>'''.
***** Selective cytologies should preferably be done, along with ureteroscopy, to allow for direct visualization of the upper urinary tracts.
**** '''In cases of unilateral upper tract cytologic abnormalities''' (with normal cystoscopy, pyelography, and bladder biopsies), '''ureteropyeloscopy is indicated as the next step'''.
***** Ureteropyeloscopy allows for direct visualization of small lesions and is superior to retrograde pyelography in the detection of small tumors.
***** '''Biopsy at the time of ureteropyeloscopy should be attempted, if feasible. A persistently abnormal cytology without any visualized lesions may signify CIS'''.