Upper Urinary Tract Urothelial Cancer: Difference between revisions
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** In males, this could include one or both upper urinary tracts and/or the prostatic urethra | ** In males, this could include one or both upper urinary tracts and/or the prostatic urethra | ||
** In females, this could be the bladder and both upper urinary tracts. | ** In females, this could be the bladder and both upper urinary tracts. | ||
** Low incidence | ** Low incidence, limited data on outcomes | ||
== Epidemiology == | == Epidemiology == | ||
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** '''M:F 2:1 (unlike bladder which is M:F 4:1)[https://seer.cancer.gov/statistics-network/explorer/application.html]''' | ** '''M:F 2:1 (unlike bladder which is M:F 4:1)[https://seer.cancer.gov/statistics-network/explorer/application.html]''' | ||
* Race | * Race | ||
** Whites are 2x more likely than Blacks to develop UTUC | ** US Whites are 2x more likely than Blacks to develop UTUC | ||
== Risk Factors == | == Risk Factors == | ||
=== | === <span style="color:#ff0000">Hereditary (1)</span> === | ||
# <strong><span style="color:#ff0000">[[Lynch syndrome]] (hereditary nonpolyposis colorectal carcinoma (HNPCC))</span></strong> | # <strong><span style="color:#ff0000">[[Lynch syndrome]] (hereditary nonpolyposis colorectal carcinoma (HNPCC))</span></strong> | ||
#* <strong>Compared with non-hereditary cancers, patients are younger (mean age 55 years) and are more likely to be female</strong> | #* <strong>Compared with non-hereditary cancers, patients are younger (mean age 55 years) and are more likely to be female</strong> | ||
#* '''Account for 7-20% of U.S. cases''' | |||
=== <span style="color:#ff0000">Acquired (8)</span> === | === <span style="color:#ff0000">Acquired (8)</span> === | ||
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*#* '''Primary upper urinary tract tumors are uncommon''' | *#* '''Primary upper urinary tract tumors are uncommon''' | ||
*#**'''Most UTUC occur as secondary tumors that present after NMIBC'''[https://pubmed.ncbi.nlm.nih.gov/11956428/] | *#**'''Most UTUC occur as secondary tumors that present after NMIBC'''[https://pubmed.ncbi.nlm.nih.gov/11956428/] | ||
*#*'''<span style="color:#ff0000">2-4% patients with bladder cancer will subsequently develop UTUC</span>''' | *#*'''<span style="color:#ff0000">Even though UTUC is more common after bladder cancer than primary UTUC, few (2-4%) patients with bladder cancer will subsequently develop UTUC</span>''' | ||
*#**'''Potential explanations on why bladder cancers following UTUC are more common than UTUC following bladder cancer include:''' | |||
*#**# '''Downstream seeding''' | |||
*#**# '''Longer exposure time to carcinogens in the bladder''' | |||
*#**# '''Greater number of urothelial cells in the bladder that are subject to random carcinogenic events''' | |||
*#**Interval ranges from 17-170 months | *#**Interval ranges from 17-170 months | ||
*#**'''Risk factors for subsequent UTUC in patients undergoing cystectomy for bladder cancer[https://pubmed.ncbi.nlm.nih.gov/23083867/]''' | *#**'''Risk factors for subsequent UTUC in patients undergoing cystectomy for bladder cancer[https://pubmed.ncbi.nlm.nih.gov/23083867/]''' | ||
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* '''<span style="color:#ff0000">Unique to UTUC (1):</span>''' | * '''<span style="color:#ff0000">Unique to UTUC (1):</span>''' | ||
*# '''<span style="color:#ff0000">Aristolochic acid</span>[https://pubmed.ncbi.nlm.nih.gov/23462915/]''' | *# '''<span style="color:#ff0000">Aristolochic acid</span>[https://pubmed.ncbi.nlm.nih.gov/23462915/]''' | ||
*#* Found in plants (Aristolochia fangchi and Aristolochia clematitis) and has mutagenic action | *#* Found in plants (Aristolochia fangchi and Aristolochia clematitis) and has mutagenic action | ||
*#** Associated mutation is predominant in patients with Balkan endemic nephropathy and Chinese herb nephropathy. | |||
*#** These plants are endemic in Balkan (Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Kosovo, Montenegro, North Macedonia, Romania, Serbia, and Slovenia) countries and grow as weeds in wheat fields. | |||
*#* Incidence of Balkan endemic nephropathy is decreasing. | |||
== Embryology == | |||
*'''Bladder is derived from the endoderm''' | |||
* '''Ureter and renal pelvis are derived from the mesoderm''' | |||
== Histology == | == Histology == | ||
=== Normal upper tract urothelium === | === Normal upper tract urothelium === | ||
* ''' | * '''Urothelium''' | ||
* The urothelial lining of the upper urinary tract | ** '''The urothelial lining of the upper urinary tract is similar to that of the bladder except for (2):''' | ||
* The | **# '''Markedly reduced thickness of the muscle layer''' | ||
** It has been suggested that the urothelial layer may even “extend” into the collecting ducts, raising the possibility that collecting duct renal cancers may be closely related to urothelial cancers and perhaps better treated by agents used for urothelial cancers | **# '''Abutting of the urothelium to the renal parenchyma proximally''' | ||
* | ** The urothelial layer is continuous from the level of the calyces to the distal ureter. | ||
** | *** It has been suggested that the urothelial layer may even “extend” into the collecting ducts, raising the possibility that collecting duct renal cancers may be closely related to urothelial cancers and perhaps better treated by agents used for urothelial cancers | ||
* Renal pelvis and calyces | |||
** The walls of the calyces and the pelvis contain fibrous connective tissue and 2 layers of smooth muscle and are lined on their inner surfaces with urothelium | |||
* Ureter | * Ureter | ||
** The 3 muscular layers of the ureter merge with the 3 muscular layers of the bladder | ** The 3 muscular layers of the ureter merge with the 3 muscular layers of the bladder | ||
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=== Abnormal urothelium === | === Abnormal urothelium === | ||
==== Benign | ==== Benign ==== | ||
===== Papillomas and inverted papillomas ===== | |||
* '''Generally considered benign lesions''' | |||
* '''<span style="color:#ff0000">Associated with either synchronous or metachronous UTUC''' | |||
** '''<span style="color:#ff0000">Follow-up for all cases of inverted papilloma should be continued for at least 2 years after initial diagnosis</span>''' | |||
===== Von Brunn Nests ===== | |||
* '''Reactive proliferation, considered a variation of normal urothelium.''' | |||
==== Metaplasia and dysplasia ==== | ==== Metaplasia and dysplasia ==== | ||
* '''<span style="color:#ff0000">In a significant proportion of patients, UTUCs progress from hyperplasia to dysplasia to frank CIS</span>''' | * '''<span style="color:#ff0000">In a significant proportion of patients, UTUCs progress from hyperplasia to dysplasia to frank CIS</span>''' | ||
==== Urothelial carcinoma ==== | ==== Malignant ==== | ||
===== Urothelial carcinoma ===== | |||
* '''<span style="color:#ff0000">Majority (90%) of upper tract tumours are urothelial carcinoma</span>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308053/]''' | * '''<span style="color:#ff0000">Majority (90%) of upper tract tumours are urothelial carcinoma</span>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308053/]''' | ||
** Squamous and adenocarcinomas comprise a small minority. | ** Squamous and adenocarcinomas comprise a small minority. | ||
* '''UTUC are histologically similar to urothelial carcinoma of the bladder, but <span style="color:#ff0000">the relative thinness of the muscle layer of the renal pelvis and ureter may allow earlier penetration of invasive upper tract tumors than is seen in bladder neoplasms.</span>''' | * '''UTUC are histologically similar to urothelial carcinoma of the bladder, but <span style="color:#ff0000">the relative thinness of the muscle layer of the renal pelvis and ureter may allow earlier penetration of invasive upper tract tumors than is seen in bladder neoplasms.</span>''' | ||
** '''<span style="color:#ff0000">UTUC is more often invasive and poorly differentiated than bladder cancers. However, in pathologically matched cohorts, cancer-specific outcomes are comparable between urothelial tumours of the upper tract and bladder</span>''' | ** '''<span style="color:#ff0000">UTUC is more often invasive and poorly differentiated than bladder cancers. However, in pathologically matched cohorts, cancer-specific outcomes are comparable between urothelial tumours of the upper tract and bladder</span>''' | ||
* '''Reported variants of urothelial carcinoma are squamous cell, glandular, sarcomatoid, micropapillary, neuroendocrine, and lymphoepithelial'''. | * '''Variant histology''' | ||
** '''Reported variants of urothelial carcinoma are squamous cell, glandular, sarcomatoid, micropapillary, neuroendocrine, and lymphoepithelial'''. | |||
** Although all of these variants are considered aggressive tumors, after adjustment for the rest of clinicopathologic characteristics, '''<span style="color:#ff0000">variant histology has not been shown to predict poor clinical outcome in UTUC (unlike bladder cancer)</span>''' | ** Although all of these variants are considered aggressive tumors, after adjustment for the rest of clinicopathologic characteristics, '''<span style="color:#ff0000">variant histology has not been shown to predict poor clinical outcome in UTUC (unlike bladder cancer)</span>''' | ||
==== Non-urothelial carcinoma ==== | ===== Non-urothelial carcinoma ===== | ||
* '''<span style="color:#ff0000">Most commonly squamous cell carcinoma and adenocarcinoma</span>''' | * '''<span style="color:#ff0000">Most commonly squamous cell carcinoma and adenocarcinoma</span>''' | ||
===== Squamous ===== | ====== Squamous ====== | ||
* '''Frequently associated with | * '''Frequently associated with''' | ||
*# '''Chronic inflammation''' | |||
*# '''Chronic infection''' | |||
*# '''Analgesic abuse''' | |||
* '''Typically more aggressive at presentation''' | * '''Typically more aggressive at presentation''' | ||
* Occur 6x more frequently in the renal pelvis than in the ureter | * Occur 6x more frequently in the renal pelvis than in the ureter | ||
===== Adenocarcinoma ===== | ====== Adenocarcinoma ====== | ||
* Rare | * Rare | ||
* '''Typically associated with | * '''Typically associated with''' | ||
*# '''Chronic inflammation''' | |||
*# '''Urinary calculi''' | |||
*# '''Chronic obstruction''' | |||
== TNM staging ([https://www.facs.org/quality-programs/cancer/ajcc/cancer-staging/form-supplement AJCC 8th edition]) == | == TNM staging ([https://www.facs.org/quality-programs/cancer/ajcc/cancer-staging/form-supplement AJCC 8th edition]) == | ||
=== <span style="color:#ff0000">Tumor (T) stage</span> === | |||
* <strong>TX: tumour cannot be assessed</strong> | |||
* <strong>T0: no evidence of tumour</strong> | |||
* <strong><span style="color:#ff0000">Ta: non-invasive (confined to epithelial mucosa) papillary carcinoma</span></strong> | |||
* <strong><span style="color:#ff0000">Tis: carcinoma in-situ</span></strong> | |||
* <strong><span style="color:#ff0000">T1: invades lamina propria </span></strong>(subepithelial connective tissue) | |||
* <strong><span style="color:#ff0000">T2: invades muscle</span></strong> | |||
* <strong><span style="color:#ff0000">T3</span></strong> | |||
** <strong><span style="color:#ff0000">Renal pelvis: tumour invades beyond muscularis into peripelvic fat or renal parenchyma</span></strong> | |||
** <strong><span style="color:#ff0000">Ureter: tumour invades beyond muscularis into periureteric fat</span></strong> | |||
* <strong><span style="color:#ff0000">T4: invades adjacent organs or through the kidney into perinephric fat</span></strong> | |||
=== Nodal (N) stage === | |||
* NX: regional lymph nodes cannot be assessed | |||
* N0: no regional lymph node metastasis | |||
* N1: metastasis ≤2 cm in greatest dimension, in a single lymph node | |||
* N2: metastasis >2 cm in a single lymph node; or multiple lymph nodes | |||
=== Metastasis (M) stage === | |||
* MX: distant metastasis cannot be assessed | |||
* M0: no distant metastasis | |||
* M1: distant metastasis | |||
== Natural history == | == Natural history == | ||
* At the time of diagnosis | |||
*At the time of diagnosis | |||
** ≈25% will present as localized disease | ** ≈25% will present as localized disease | ||
** >50% will present as regionally advanced cancers | ** >50% will present as regionally advanced cancers | ||
** ≈20% will present as distant disease | ** ≈20% will present as distant disease | ||
* '''Most occurrences are in a single renal unit''' | |||
** '''Synchronous bilateral UTUC is rare (<2%)''' | |||
*** CIS increases risk of bilateral disease and multifocality | |||
** Metachronous UTUC occurrences are 80% after bladder cancer and 2-6% after contralateral UTUC | |||
*'''UTUC may spread''' in the same ways as bladder tumors do via '''direct invasion into the renal parenchyma or surrounding structures, lymphatic or hematogenous invasion, and epithelial spread by seeding or direct extension.''' | *'''UTUC may spread''' in the same ways as bladder tumors do via '''direct invasion into the renal parenchyma or surrounding structures, lymphatic or hematogenous invasion, and epithelial spread by seeding or direct extension.''' | ||
** '''<span style="color:#ff0000">Lymphatic:</span>''' | ** '''<span style="color:#ff0000">Lymphatic:</span>''' | ||
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**** Antegrade seeding is more common and thought to be the most likely explanation for the high incidence of recurrence in patients in whom a ureteral stump is left in situ after nephrectomy and incomplete ureterectomy | **** Antegrade seeding is more common and thought to be the most likely explanation for the high incidence of recurrence in patients in whom a ureteral stump is left in situ after nephrectomy and incomplete ureterectomy | ||
== Diagnosis and Evaluation | == Diagnosis and Evaluation == | ||
=== <span style="color:#ff0000">UrologySchool.com Summary</span> === | === <span style="color:#ff0000">UrologySchool.com Summary</span> === | ||
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==== History ==== | ==== History ==== | ||
===== Signs and Symptoms ===== | |||
* '''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">Risk factors</span> ===== | |||
* <span style="color:#ff0000">''' | * '''Acquired (see above)'''</span> | ||
** <span style="color:#ff0000">''' | * <span style="color:#ff0000">'''Hereditary (personal and family history)'''</span> | ||
** <span style="color:#ff0000">'''Identify familial diseases associated with Lynch Syndrome'''</span> | |||
***'''If positive, referral for genetic counseling should be offered.[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | ***'''If positive, referral for genetic counseling should be offered.[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | ||
***'''<span style="color:#ff0000">Lynch syndrome</span>''' | ***'''<span style="color:#ff0000">Lynch syndrome</span>''' | ||
****'''See [[Lynch syndrome|Lynch Syndrome Chapter Notes]]''' | |||
****Familial, autosomal-dominant multi-organ cancer syndrome | ****Familial, autosomal-dominant multi-organ cancer syndrome | ||
****''' | ****'''Patients 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/]''' | ||
**** | ****May increase the possibility of contralateral upper tract involvement, which is an important potential clinical consideration when developing a treatment plan | ||
=== Labs === | === Labs === | ||
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****#Avoid potential contamination in case of concomitant bladder and/or prostatic urethral disease | ****#Avoid potential contamination in case of concomitant bladder and/or prostatic urethral disease | ||
****#Avoid theoretical dilution of the specimen from a normal contralateral unit | ****#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. | ***'''Voided cytology''' | ||
****'''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> ==== | ==== <span style="color:#ff0000">Assessment of renal function</span> ==== | ||
*Can help with | *Can help with | ||
*#Patient counseling | |||
*#Strategizing treatment sequence (operative approach and administration of systemic therapy) | |||
*#Determination of downstream risks of CKD and potential dialysis | |||
* '''<span style="color:#ff0000">Recommended test: serum creatinine (to calculate an eGFR)''' | * '''<span style="color:#ff0000">Recommended test: serum creatinine (to calculate an eGFR)''' | ||
**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. | |||
**For more refined evaluation, split function testing such as with differential renal scan or CT volumetric studies may be considered. | **For more refined evaluation, split function testing such as with differential renal scan or CT volumetric studies may be considered. | ||
*'''<span style="color:#ff0000">Special scenarios''' | |||
*'''<span style="color:#ff0000"> | **'''<span style="color:#ff0000">UTUC with associated hydronephrosis''' | ||
**''' | ***Tumor obstruction may falsely under-estimate preoperative renal function and alter decision-making around the use of neoadjuvant chemotherapy (NAC). | ||
*** | ***'''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''' | ||
**'''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.''' | *****Percutaneous nephrostomy tubes in the setting of UTUC increases risk of tract seeding and has worse quality of life | ||
***'''<span style="color:#ff0000">Ureteric stenting is the preferred method of drainage''' | **'''Atrophy of the contralateral (unaffected) renal unit''' | ||
****Percutaneous nephrostomy tubes in the setting of UTUC increases risk of tract seeding and has worse quality of life | ***'''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''' | ||
=== Imaging === | === Imaging === | ||
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**'''<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">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>''' | ||
====== | ====== CT urography ====== | ||
* '''<span style="color:#ff0000">Typical findings suggestive of an upper urinary tract tumor (3):''' | |||
*'''Typical findings suggestive of an upper urinary tract tumor (3):''' | *# '''<span style="color:#ff0000">Radiolucent filling defects''' | ||
*# '''Radiolucent filling defects''' | *# '''<span style="color:#ff0000">Non-visualization of the collecting system''' | ||
*# '''Non-visualization of the collecting system''' | *# '''<span style="color:#ff0000">Obstruction''' | ||
*# '''Obstruction''' | [[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">Differential diagnosis of | * '''<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</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">Blood clot</span>''' | ||
*# '''<span style="color:#ff0000">Stones</span>'''; higher HFU than urothelial carcinoma | *# '''<span style="color:#ff0000">Suburothelial hemorrhage</span>''' | ||
*# '''<span style="color:#ff0000"> | *#'''<span style="color:#ff0000">Stones</span>'''; higher HFU than urothelial carcinoma | ||
*# '''<span style="color:#ff0000">Fungus ball</span>''' | *# '''<span style="color:#ff0000">Renal papillary necrosis/sloughed papilla</span>''' | ||
*# '''<span style="color:#ff0000"> | *# '''<span style="color:#ff0000">Hypertrophied papilla</span>''' | ||
*# '''<span style="color:#ff0000"> | *#'''<span style="color:#ff0000">Inflammation</span>''' | ||
* '''Urothelial cancers | *#'''<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''' | |||
** '''Enhance on arterial/early nephrographic phase, dark/filling defect in urographic phase.''' | |||
**'''More infiltrative features compared to RCC''' | |||
*'''Radiolucent, noncalcified lesions may require additional evaluation by retrograde urography or ureteroscopy, with or without biopsy and cytology''' | *'''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">Important to evaluate contralateral kidney to assess (2):''' | ||
**'''<span style="color:#ff0000">Possible bilateral disease''' | **'''<span style="color:#ff0000">Possible bilateral disease''' | ||
**'''<span style="color:#ff0000">Functionality of the contralateral kidney''' | **'''<span style="color:#ff0000">Functionality of the contralateral kidney''' | ||
==== <span style="color:#ff0000">Metastasis</span> ==== | |||
* '''<span style="color:#ff0000">Chest X-Ray</span>''' | * '''<span style="color:#ff0000">Chest X-Ray</span>''' | ||
* '''Bone scan,''' consider in the presence of bone pain, elevated calcium or elevated alkaline phosphatase | * '''Bone scan,''' consider in the presence of bone pain, elevated calcium or elevated alkaline phosphatase | ||
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==== <span style="color:#ff0000">Cystoscopy</span> ==== | ==== <span style="color:#ff0000">Cystoscopy</span> ==== | ||
*'''<span style="color:#ff0000">Mandatory | *'''<span style="color:#ff0000">Mandatory since most UTUC are associated with bladder cancers</span>''' | ||
==== <span style="color:#ff0000">Upper tract endoscopy +/- biopsy of any identified lesion</span> ==== | ==== <span style="color:#ff0000">Upper tract endoscopy +/- biopsy of any identified lesion</span> ==== | ||
*'''<span style="color:#ff0000"> | |||
**''' | ===== Rationale ===== | ||
** | |||
**#''' | * '''URS allows direct visualization of the tumor and biopsy of suspected areas''' | ||
** | |||
[[File:Cystoscopy - Uretereal Cancer.jpg|center|Ureteral tumour on endoscopy. [[commons:File:Cystoscopy_-_Uretereal_Cancer.jpg|Source]]|thumb|637x637px]] | |||
** | |||
*** '''<span style="color:#ff0000"> | ===== Indications[https://pubmed.ncbi.nlm.nih.gov/37096584/] ===== | ||
***#'''<span style="color:#ff0000">Location (ureteral segment, renal pelvis, calyceal sites and lower tract)''' | #'''Radiographic presence of a mass or urothelial thickening''' | ||
***#'''<span style="color:#ff0000">Size''' | #'''Lateralizing hematuria''' | ||
***#'''<span style="color:#ff0000">Number''' | #'''Suspicious selective cytology''' | ||
***#'''<span style="color:#ff0000">Focality''' | '''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. | |||
===== Biopsy ===== | |||
*'''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''' | |||
**'''<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%) | |||
**'''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>''' | |||
===== 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. | |||
**** '''If the ureter does not accept the smaller ureteroscope, active dilation of the ureter is necessary.''' | |||
**** '''<span style="color:#ff0000">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. | |||
*** The flexible ureteroscope is used to visualize the remaining urothelium. | |||
*** '''<span style="color:#ff0000">When a lesion or suspicious area is seen, document key descriptive features 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">Appearance (sessile, papillary, flat/villous)''' | ||
***#'''<span style="color:#ff0000">Quality of visualization | ***# '''<span style="color:#ff0000">Quality of visualization''' | ||
***#*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. | ***#* 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 | ***# See checklist in 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 | ***# 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 | ||
*** | *** Before biopsy or intervention, perform a normal saline wash. | ||
**'''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 | |||
*'''Special scenarios''' | |||
**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 | |||
*** | |||
* | |||
** | |||
** | |||
**'''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/]''' | **'''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. | ***Consensus on prioritization of procedure sequencing (managing bladder before or after same-setting ureteroscopy) is lacking and heavily scenario-dependent. | ||
| Line 373: | Line 434: | ||
***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 | ***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. | ****The benefits of this approach require further prospective study. | ||
** ''' | **'''Ureteroscopy cannot be safely performed or is not possible''' | ||
* | ***'''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. | |||
**''' | |||
***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. | |||
===== 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''' | |||
** '''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/]''' | |||
==== <span style="color:#ff0000">Universal histologic testing of UTUC with additional studies, such as immunohistochemical (IHC) or microsatellite instability (MSI)</span> ==== | ==== <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/]''' | *'''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/]''' | ||
| Line 401: | Line 449: | ||
***Widely available | ***Widely available | ||
**Microsatellite instability | **Microsatellite instability | ||
***Identifying the presence of Lynch syndrome-associated and MSI-high cancers | ***Identifying the presence of Lynch syndrome-associated and MSI-high cancers 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> ==== | ==== <span style="color:#ff0000">Percutaneous biopsy</span> ==== | ||
| Line 407: | Line 455: | ||
* Safe and effective technique[https://pubmed.ncbi.nlm.nih.gov/24905868/ §] | * 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/ §] | *Consider for upper tract urothelial lesions which are not amenable to endoscopic biopsy[https://pubmed.ncbi.nlm.nih.gov/24905868/ §] | ||
==== Urine fluorescence in situ hybridization (FISH) ==== | ==== Urine fluorescence in situ hybridization (FISH) ==== | ||
| Line 432: | Line 479: | ||
***** Ureteropyeloscopy allows for direct visualization of small lesions and is superior to retrograde pyelography in the detection of small tumors. | ***** 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'''. | ***** '''Biopsy at the time of ureteropyeloscopy should be attempted, if feasible. A persistently abnormal cytology without any visualized lesions may signify CIS'''. | ||
****** '''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''' | |||
== Risk-Stratification of Localized UTUC == | == Risk-Stratification of Localized UTUC == | ||
| Line 441: | Line 487: | ||
** '''<span style="color:#ff0000">Categorized as high- vs. low-risk</span>''' of disease progression and pathologic stage ≥T2 disease | ** '''<span style="color:#ff0000">Categorized as high- vs. low-risk</span>''' of disease progression and pathologic stage ≥T2 disease | ||
***'''<span style="color:#ff0000">Based on biopsy grade</span>''' | ***'''<span style="color:#ff0000">Based on biopsy grade</span>''' | ||
**** | ****Due to strong association of high grade tumor on ureteroscopic biopsy with high-stage disease (≥pT2) on final pathology (positive predictive value: 60%; negative predictive value: 77%) | ||
***'''<span style="color:#ff0000">Sub-stratified into favorable vs. unfavorable (see [https://www.auajournals.org/doi/10.1097/JU.0000000000003480 Table 4])</span>''' | |||
****'''<span style="color:#ff0000">Based on (4):</span>''' | |||
***'''<span style="color:#ff0000">Sub-stratified into favorable vs. unfavorable (see [https://www.auajournals.org/doi/10.1097/JU.0000000000003480 Table 4]) | ****#'''<span style="color:#ff0000">Cytology</span>''' | ||
***#'''<span style="color:#ff0000">Cytology</span>''' | ****#'''<span style="color:#ff0000">Radiographic appearance (6)</span>''' | ||
***#'''<span style="color:#ff0000">Radiographic appearance</span>''' | ****##'''<span style="color:#ff0000">Multifocality</span>''' | ||
***# | ****##'''<span style="color:#ff0000">Size</span>''' | ||
***# | ****##'''<span style="color:#ff0000">Invasive features</span>''' | ||
***# | ****##*Heterogenous texture on enhanced and even unenhanced CT imaging has been associated with invasive disease | ||
***# | ****##'''<span style="color:#ff0000">Obstruction of the urinary tract</span>''' | ||
***# | ****##'''<span style="color:#ff0000">Locoregional progression such as suspicious lymphadenopathy</span>''' | ||
***# | ****##'''<span style="color:#ff0000">Presence of metastatic disease</span>''' | ||
***# | ****#'''<span style="color:#ff0000">Endoscopic appearance</span>''' | ||
***#'''<span style="color:#ff0000">Endoscopic appearance</span>''' | ****##'''<span style="color:#ff0000">Appearance (sessile, papillary, flat/villous)</span>''' | ||
***# | ****##'''<span style="color:#ff0000">Multifocality</span>''' | ||
***# | ****##'''<span style="color:#ff0000">Size</span>''' | ||
***# | ****##*'''Tumors ≥ 1.5 cm in size are associated with a > 80% risk of invasive disease''' | ||
***#* | ****##*Measurement in the pre-surgical setting is not standardized and has not been shown to be independent of other more easily determined clinically identified features such as multifocality, invasion and obstruction. | ||
***# | ****#'''<span style="color:#ff0000">Lower tract involvement</span>''' | ||
***#'''<span style="color:#ff0000">Lower tract involvement</span>''' | ****#*Pan-urothelial disease as indicated by history of prior cystectomy, concomitant or metachronous lower tract urothelial cancer or contralateral UTUC diagnosis | ||
***#* | [[File:UTUC_riskstratification.jpg|center|thumb|875x875px|UTUC Risk Stratification]] | ||
== Management == | == Management == | ||
| Line 487: | Line 533: | ||
=====Endoscopic Ablation/Resection===== | =====Endoscopic Ablation/Resection===== | ||
====== Advantages ====== | |||
# '''Minimally-invasive''' | |||
# '''Preserves renal function''' | |||
====== Disadvantages ====== | |||
# '''High risk of recurrence''' | |||
# '''Risk of disease progression remains''' | |||
#* '''Due to the suboptimal performance of imaging and biopsy for risk stratification and tumour biology''' | |||
====== Technical considerations ====== | ====== Technical considerations ====== | ||
| Line 542: | Line 589: | ||
**** Complications from percutaneous management of tumors are similar to those for benign renal processes and include bleeding, systemic absorption of hypo-osmotic irrigation (with monopolar resection), perforation of the collecting system, and secondary ureteropelvic junction obstruction. | **** Complications from percutaneous management of tumors are similar to those for benign renal processes and include bleeding, systemic absorption of hypo-osmotic irrigation (with monopolar resection), perforation of the collecting system, and secondary ureteropelvic junction obstruction. | ||
*'''Tumor size[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | *'''Tumor size[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | ||
** '''Tumors < 1.5 cm in size may be optimal for endoscopic ablation given a lower risk of invasive disease.''' | ** '''<span style="color:#ff0000">Tumors < 1.5 cm in size may be optimal for endoscopic ablation given a lower risk of invasive disease.''' | ||
*** Tumors ≥ 1.5 cm in size are associated with a > 80% risk of invasive disease | *** Tumors ≥ 1.5 cm in size are associated with a > 80% risk of invasive disease | ||
***'''Larger tumors (≥ 1.5 cm) may be considered for ablation based on the provider’s experience and assessment of the need for kidney sparing surgery.''' | ***'''Larger tumors (≥ 1.5 cm) may be considered for ablation based on the provider’s experience and assessment of the need for kidney sparing surgery.''' | ||
*Energy source[https://pubmed.ncbi.nlm.nih.gov/37096584/] | *Energy source[https://pubmed.ncbi.nlm.nih.gov/37096584/] | ||
**Can be performed with laser or electrocautery | **Can be performed with laser or electrocautery | ||
***Electrocautery | ***Laser | ||
**** | ****Thulium, holmium (Ho:YAG), and Neodymium (Nd:YAG) are laser energies that have been used | ||
***Electrocautery | |||
****Delivered through a small Bugbee electrode (2 or 3 Fr) | |||
****Variable depth of penetration can make its use in the ureter dangerous | |||
****Circumferential fulguration should be avoided because of the high risk of stricture formation. | |||
* Chemoablation[https://pubmed.ncbi.nlm.nih.gov/37096584/] | * Chemoablation[https://pubmed.ncbi.nlm.nih.gov/37096584/] | ||
**May be employed either through retrograde ureteral catheter instillation or percutaneous access with fluoroscopic imaging guidance | **May be employed either through retrograde ureteral catheter instillation or percutaneous access with fluoroscopic imaging guidance | ||
*Ureteral access sheath[https://pubmed.ncbi.nlm.nih.gov/37096584/] | *'''Ureteral access sheath[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | ||
**Prior to placement of any ureteral access sheath, the entire ureter should be directly visualized in order to avoid missing any luminal neoplasms, especially in the distal ureter | **'''<span style="color:#ff0000">Prior to placement of any ureteral access sheath, the entire ureter should be directly visualized in order to avoid missing any luminal neoplasms, especially in the distal ureter''' | ||
** Advantages (3): | ** Advantages (3): | ||
**#Allows for repeated scope passage up and down the ureter for sampling | **#Allows for repeated scope passage up and down the ureter for sampling | ||
| Line 575: | Line 625: | ||
**** Recurrence-free and cancer-specific survival outcomes worsened with increasing grade | **** Recurrence-free and cancer-specific survival outcomes worsened with increasing grade | ||
*** [https://pubmed.ncbi.nlm.nih.gov/22471401/ Cutress, Mark L., et al. "Ureteroscopic and percutaneous management of upper tract urothelial carcinoma (UTUC): systematic review." ''BJU international'' 110.5 (2012): 614-628.] | *** [https://pubmed.ncbi.nlm.nih.gov/22471401/ Cutress, Mark L., et al. "Ureteroscopic and percutaneous management of upper tract urothelial carcinoma (UTUC): systematic review." ''BJU international'' 110.5 (2012): 614-628.] | ||
* '''Given high risk of recurrence with endoscopic management, patients should be informed of the need for early second-look and stringent surveillance.''' | * '''<span style="color:#ff0000">Given high risk of recurrence with endoscopic management, patients should be informed of the need for early second-look and stringent surveillance.''' | ||
======Adjuvant therapy====== | ======Adjuvant therapy====== | ||
| Line 592: | Line 642: | ||
====== Indications (3): ====== | ====== Indications (3): ====== | ||
# '''Adjuvant therapy after endoscopic or organ-sparing therapy''' | # '''<span style="color:#ff0000">Adjuvant therapy after endoscopic or organ-sparing therapy''' | ||
#'''Primary treatment for CIS (see Special Scenarios)''' | #'''<span style="color:#ff0000">Primary treatment for CIS (see Special Scenarios)''' | ||
# '''Primary treatment of low-grade UTUC (UGN-101)''' | # '''<span style="color:#ff0000">Primary treatment of low-grade UTUC (UGN-101)''' | ||
====== Adjuvant therapy ====== | ====== Adjuvant therapy ====== | ||
*'''Pelvicalyceal or intravesical chemotherapy following ablation of UTUC tumors[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | *'''Pelvicalyceal or intravesical chemotherapy following ablation of UTUC tumors[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | ||
**Principle of an immediate instillation of intravesical or | **Principle of an immediate instillation of intravesical or upper tract chemotherapy at the time of endoscopic tumor ablation is extrapolated from the data supporting immediate instillation of intravesical chemotherapy at the time of transurethral resection of a bladder tumor | ||
**Options: | **Options: | ||
***Thiotepa | |||
***Mitomycin | |||
**'''Indications''' | **'''Indications''' | ||
*** '''Considered optional''' | *** '''Considered optional''' | ||
| Line 659: | Line 711: | ||
***** 37% had ≥1 serious adverse event | ***** 37% had ≥1 serious adverse event | ||
****** '''44% ureteric stenosis[https://pubmed.ncbi.nlm.nih.gov/34915741/]''' | ****** '''44% ureteric stenosis[https://pubmed.ncbi.nlm.nih.gov/34915741/]''' | ||
******* '''Use of chemoablative treatment with the reverse thermo-hydrogel preparation of mitomycin for pyelocaliceal instillation for LG tumors carries an FDA label warning for ureteral obstruction, bone marrow suppression, and embryo-fetal toxicity.''' | |||
****** 20% renal dysfunction | ****** 20% renal dysfunction | ||
*** [https://pubmed.ncbi.nlm.nih.gov/32631491/ Kleinmann, Nir, et al.] "Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial." ''The lancet oncology'' 21.6 (2020): 776-785. | *** [https://pubmed.ncbi.nlm.nih.gov/32631491/ Kleinmann, Nir, et al.] "Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial." ''The lancet oncology'' 21.6 (2020): 776-785. | ||
| Line 668: | Line 721: | ||
*** Both the antegrade and retrograde approach can be dangerous due to possible ureteric obstruction and consecutive pyelovenous influx during instillation/perfusion. | *** Both the antegrade and retrograde approach can be dangerous due to possible ureteric obstruction and consecutive pyelovenous influx during instillation/perfusion. | ||
=====Segmental Ureterectomy===== | =====Segmental Ureterectomy===== | ||
====== Options ====== | ====== Options ====== | ||
*'''<span style="color:#ff0000">Segmental ureterectomy with ureteroureterostomy</span>''' | *'''<span style="color:#ff0000">Segmental ureterectomy with ureteroureterostomy</span>''' | ||
** '''<span style="color:#ff0000"> | ** '''<span style="color:#ff0000">Patients most suitable for segmental ureterectomy have small, unifocal tumors (typically 1 cm or smaller) tumors isolated to a short segment of the proximal or mid-ureter requiring resection of 2 cm or less of ureteral length to allow for primary</span>''' | ||
***Longer sections of ureteral involvement and resection may require more complex reconstruction techniques when kidney sparing is desired. | ***Longer sections of ureteral involvement and resection may require more complex reconstruction techniques when kidney sparing is desired. | ||
*'''<span style="color:#ff0000">Distal ureterectomy with ureteral reimplant</span>''' | *'''<span style="color:#ff0000">Distal ureterectomy with ureteral reimplant</span>''' | ||
| Line 691: | Line 742: | ||
====== Outcomes ====== | ====== Outcomes ====== | ||
* '''<span style="color:#ff00ff">Systematic review and meta-analysis comparing segmental resection to radical nephroureterectomy (2020)</span>''' | * '''Reasonable alternative to RNU for well-selected patients''' | ||
** Results: | ** '''<span style="color:#ff00ff">Systematic review and meta-analysis comparing segmental resection to radical nephroureterectomy (2020)</span>''' | ||
*** Included 18 studies comprising 4797 patients, of which 1313 underwent segmental resection | *** Results: | ||
*** High risk of bias across all domains | **** Included 18 studies comprising 4797 patients, of which 1313 underwent segmental resection | ||
*** 5-yr: | **** High risk of bias across all domains analyzed, limiting interpretation of comparisons | ||
**** Recurrence-free survival: significantly worse with segmental resection | **** 5-yr: | ||
**** Cancer-specific survival: no significant difference | ***** Recurrence-free survival: significantly worse with segmental resection | ||
**** OS: no significant difference | ***** Cancer-specific survival: no significant difference | ||
*** Veccia, Alessandro, et al."Segmental ureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis of comparative studies." ''Clinical genitourinary cancer'' 18.1 (2020): e10-e20. | ***** OS: no significant difference | ||
*** Veccia, Alessandro, et al. "Segmental ureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis of comparative studies." ''Clinical genitourinary cancer'' 18.1 (2020): e10-e20. | |||
**'''<span style="color:#ff00ff">Systematic review and meta-analysis comparing nephron-sparing approach to radical nephroureterectomy (2016)</span>''' | |||
*** Primary outcome: cancer-specific survival | |||
*** Results | |||
**** Included 22 studies published between 1999 and 2015 | |||
***** No RCTs comparing nephron-sparing approach and nephroureterectomy | |||
**** High risk of bias across all domains analyzed, limiting interpretation of comparisons | |||
**** Segemental ureterectomy vs. RNU (10 studies): no significant difference in cancer-specific survival | |||
**** Endoscopic vs. RNU | |||
***** URS vs. RNU (5 studies): no significant difference in cancer-specific survival | |||
****** Grade-based subgroup analyses found decreased cancer-specific survival in patients undergoing URS for high-grade disease | |||
***** Percutaneous resection vs. RNU (2 studies): conflicting findings | |||
*** Seisen, Thomas, et al. "Oncologic outcomes of kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review by the EAU non-muscle invasive bladder cancer guidelines panel." ''European urology'' 70.6 (2016): 1052-1068. | |||
* Segmental ureterectomy of the proximal two-thirds of ureter is associated with higher failure rates than for the distal ureter. | * Segmental ureterectomy of the proximal two-thirds of ureter is associated with higher failure rates than for the distal ureter. | ||
====== Technique ====== | ====== Technique ====== | ||
* Risk of wound implantation by tumor is low after open segmental ureterectomy if simple precautions are followed to minimize spillage | * Risk of wound implantation by tumor is low after open segmental ureterectomy if simple precautions are followed to minimize spillage | ||
*See Segmental Ureterectomy Chapter Notes for technical aspects | *See [[Segmental ureterectomy|Segmental Ureterectomy]] Chapter Notes for technical aspects | ||
*'''When performing | *'''When performing distal ureterectomy, the entire distal ureter including the intramural ureteral tunnel and ureteral orifice should be excised, and the urinary tract should be closed in a watertight fashion.''' | ||
**The resultant hiatus in the bladder in the location of the excised ureteral orifice with or without the bladder cuff can be closed formally in a watertight fashion in one or more layers | **'''Bladder cuff excision''' | ||
***A formal BCE with watertight closure of the bladder cuff should be performed to | ***Approaches | ||
***#Avoid urinary extravasation from the bladder | ****Extravesical or transvesical (e.g., midline cystotomy) | ||
***#Facilitate more rapid catheter removal | ****Open, minimally invasive or transurethral endoscopic techniques. | ||
***#Permit instillation of intravesical adjuvant chemotherapy in the perioperative setting | *****Transurethral endoscopic approaches are associated with higher recurrence rates in the bladder and may limit the ability to utilize post-NU intravesical therapies if the bladder is not fully closed | ||
***Delayed closure by secondary intension in a decompressed bladder without formal bladder closure has also been described. | ***'''The resultant hiatus in the bladder in the location of the excised ureteral orifice with or without the bladder cuff can be closed formally in a watertight fashion in one or more layers[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | ||
****'''A formal BCE with watertight closure of the bladder cuff should be performed to''' | |||
****#'''Avoid urinary extravasation from the bladder''' | |||
****#'''Facilitate more rapid catheter removal''' | |||
****#'''Permit instillation of intravesical adjuvant chemotherapy in the perioperative setting''' | |||
****Delayed closure by secondary intension in a decompressed bladder without formal bladder closure has also been described. | |||
=====Radical nephroureterectomy with bladder cuff excision===== | =====Radical nephroureterectomy with bladder cuff excision===== | ||
====== Principles[https://pubmed.ncbi.nlm.nih.gov/37096584/] ====== | ====== Principles[https://pubmed.ncbi.nlm.nih.gov/37096584/] ====== | ||
#'''Complete excision of ipsilateral upper tract urothelium''', including the intramural portion of the ureter and ureteral orifice with negative margins | #'''Complete excision of ipsilateral upper tract urothelium''', including the intramural portion of the ureter and ureteral orifice with negative margins | ||
# | #*Specimen should be removed en bloc whenever technically feasible | ||
# '''Avoidance of urinary spillage,''' such as by early low ligation of the ureter, to minimize the risk of seeding urothelial cancer outside the urinary tract. | # '''Avoidance of urinary spillage,''' such as by early low ligation of the ureter, to minimize the risk of seeding urothelial cancer outside the urinary tract. | ||
====== Outcomes ====== | ====== Outcomes ====== | ||
*Largely dependent on clinicopathologic characteristics. | *Largely dependent on clinicopathologic characteristics. | ||
====== Technique ====== | ====== Technique ====== | ||
*See Nephroureterectomy Chapter Notes for technical aspects | *See [[Nephroureterectomy|Nephroureterectomy Chapter Notes]] for technical aspects | ||
*'''Approach[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | *'''Approach[https://pubmed.ncbi.nlm.nih.gov/37096584/]''' | ||
**Open, robotic, and laparoscopic approaches are suitable | **Open, robotic, and laparoscopic approaches are suitable | ||
***Minimally invasive approaches were associated with favorable perioperative outcomes including shorter length of stay and fewer complications, and, therefore, are favored for most patients when principles of RNU can be maintained | ***Minimally invasive approaches were associated with favorable perioperative outcomes including shorter length of stay and fewer complications, and, therefore, are favored for most patients when principles of RNU can be maintained | ||
***Consider open surgical approaches for large, bulky UTUC with clinical evidence for direct invasion to adjacent structures | ***Consider open surgical approaches for large, bulky UTUC with clinical evidence for direct invasion to adjacent structures | ||
*''' | *'''When performing NU, the entire distal ureter including the intramural ureteral tunnel and ureteral orifice should be excised, and the urinary tract should be closed in a watertight fashion.''' | ||
**Worse local and metastatic recurrence rates with associated decreased CSS and OS for patients who did not receive complete BCE. | **Worse local and metastatic recurrence rates with associated decreased CSS and OS for patients who did not receive complete BCE. | ||
====== Adverse events ====== | ====== Adverse events ====== | ||
*Range from 15% to 50% | *Range from 15% to 50% | ||
* '''30-day mortality risk | * '''30-day mortality risk: 1%''' | ||
====Treatment Selection==== | ====Treatment Selection==== | ||
| Line 756: | Line 809: | ||
=====UrologySchool.com Summary===== | =====UrologySchool.com Summary===== | ||
'''AUA''' | |||
*'''<span style="color:#ff0000">If low-risk</span>''' | *'''<span style="color:#ff0000">If low-risk</span>''' | ||
**'''<span style="color:#ff0000">Favorable</span>''' | **'''<span style="color:#ff0000">Favorable</span>''' | ||
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**'''<span style="color:#ff0000">Favorable</span>''' | **'''<span style="color:#ff0000">Favorable</span>''' | ||
***'''<span style="color:#ff0000">Surgical removal (preferred)</span>''' | ***'''<span style="color:#ff0000">Surgical removal (preferred)</span>''' | ||
***'''<span style="color:#ff0000">Tumor ablation | ***'''<span style="color:#ff0000">Tumor ablation</span>''' | ||
****'''<span style="color:#ff0000"> | ****'''<span style="color:#ff0000">Rare, select patients who have low-volume tumors or cannot undergo RNU</span>''' | ||
**'''<span style="color:#ff0000">Unfavorable</span>''' | **'''<span style="color:#ff0000">Unfavorable</span>''' | ||
***'''<span style="color:#ff0000">Surgical removal (preferred)</span>''' | ***'''<span style="color:#ff0000">Surgical removal (preferred)</span>''' | ||
**'''<span style="color:#ff0000">For surgically eligible patients with HR and unfavorable LR cancers endoscopically confirmed as confined to the lower ureter in a functional renal unit, distal ureterectomy with ureteral reimplant is the preferred treatment</span>''' | **'''<span style="color:#ff0000">For surgically eligible patients with HR and unfavorable LR cancers endoscopically confirmed as confined to the lower ureter in a functional renal unit, distal ureterectomy with ureteral reimplant is the preferred treatment</span>''' | ||
[[File:UTUT management flow.jpg|center|thumb|799x799px|UrologySchool.com Summary of UTUC Management ]] | |||
==== Patient counseling[https://pubmed.ncbi.nlm.nih.gov/37096584/] ==== | ==== Patient counseling[https://pubmed.ncbi.nlm.nih.gov/37096584/] ==== | ||
*'''<span style="color:#ff0000">Discuss and facilitate smoking cessation, if applicable,</span> with patients at the time of diagnosis and treatment.''' | *'''<span style="color:#ff0000">Discuss and facilitate smoking cessation, if applicable,</span> with patients at the time of diagnosis and treatment.''' | ||
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*'''<span style="color:#ff0000">Provide patients with a description of the short- and long-term risks associated with recommended diagnostic and therapeutic options, including</span>''' | *'''<span style="color:#ff0000">Provide patients with a description of the short- and long-term risks associated with recommended diagnostic and therapeutic options, including</span>''' | ||
*#'''<span style="color:#ff0000">Need for endoscopic follow-up</span>''' | *#'''<span style="color:#ff0000">Need for endoscopic follow-up</span>''' | ||
*#*Urothelial recurrences are common in | *#*Urothelial recurrences are common in UTUC, regardless of approach, and mandate long-term surveillance for which patients must be prepared, including the potential need for additional treatments. | ||
*# '''<span style="color:#ff0000">Risks of treatment (3)</span>''' | *# '''<span style="color:#ff0000">Risks of treatment (3)</span>''' | ||
*##'''<span style="color:#ff0000">Risk of clinically significant strictures with endoscopic management</span>''' | *##'''<span style="color:#ff0000">Risk of clinically significant strictures with endoscopic management</span>''' | ||
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* No RCTs to evaluate the effect of LND on oncologic outcomes in patients undergoing NU or SU | * No RCTs to evaluate the effect of LND on oncologic outcomes in patients undergoing NU or SU | ||
===== Indications ===== | |||
* '''AUA''' | |||
** '''<span style="color:#ff0000">Recommended (1): HR UTUC</span>''' | |||
*** Sufficient non-randomized evidence to suggest an oncologic benefit to LND at the time of NU for patients with “HR” stratification by guidelines | |||
** '''<span style="color:#ff0000">Optional (1): LR UTUC</span>''' | |||
*''' | *** Limited evidence exists to support a beneficial role for LND at time of NU or ureterectomy among patients with LR UTUC | ||
**'''Pyelocaliceal system: lymph nodes of the ipsilateral great vessel extending from the renal hilum to at least the inferior mesenteric artery.''' | |||
===== Template ===== | |||
* '''Based on tumor location''' | |||
** '''Pyelocaliceal system: lymph nodes of the ipsilateral great vessel extending from the renal hilum to at least the inferior mesenteric artery.''' | |||
**'''Proximal 2/3 of the ureter: lymph nodes of the ipsilateral great vessel extending from the renal hilum to the aortic bifurcation.''' | **'''Proximal 2/3 of the ureter: lymph nodes of the ipsilateral great vessel extending from the renal hilum to the aortic bifurcation.''' | ||
**'''Distal 1/3 of the ureter: ipsilateral pelvic LND to include at minimum the obturator and external iliac nodal packets.''' | **'''Distal 1/3 of the ureter: ipsilateral pelvic LND to include at minimum the obturator and external iliac nodal packets.''' | ||
**Internal and common iliac nodal packets may be removed in the appropriate clinical setting. | **Internal and common iliac nodal packets may be removed in the appropriate clinical setting. | ||
*Limited data suggest cranial migration of lymph node metastases to the ipsilateral great vessels such that higher dissection may be considered in the appropriate clinical setting and per clinician judgement | |||
==== Neoadjuvant/Adjuvant Therapy After Complete Excision==== | ==== Neoadjuvant/Adjuvant Therapy After Complete Excision==== | ||
=====Adjuvant intravesical chemotherapy===== | =====Adjuvant intravesical chemotherapy===== | ||
*'''<span style="color:#ff0000">In patients undergoing RNU or SU (including distal ureterectomy) for UTUC, a single dose of perioperative intravesical chemotherapy should be administered | *'''<span style="color:#ff0000">In patients undergoing RNU or SU (including distal ureterectomy) for UTUC, a single dose of perioperative intravesical chemotherapy should be administered to reduce the risk of bladder recurrence.[https://pubmed.ncbi.nlm.nih.gov/37096584/]</span>''' | ||
**The exact timing of therapy has varied including instilling intravesical chemotherapy at the time of catheter removal (ODMIT-C trial), while other retrospective series reported instillation during surgery or up to 48 hours postoperatively. | **The exact timing of therapy has varied including instilling intravesical chemotherapy at the time of catheter removal (ODMIT-C trial), while other retrospective series reported instillation during surgery or up to 48 hours postoperatively. | ||
***'''<span style="color:#ff00ff">ODMIT-C (2011)</span>''' | ***'''<span style="color:#ff00ff">ODMIT-C (2011)</span>''' | ||
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=====Systemic Therapy===== | =====Systemic Therapy===== | ||
====== Neoadjuvant ====== | |||
* '''No randomized trials evaluating benefit of neoadjuvant therapy for UTUC.''' | |||
* '''Chemotherapy''' | |||
** The use of agents for UTUC has been extrapolated from chemotherapy regimens used in bladder urothelial cancer | |||
** '''<span style="color:#ff0000">Cisplatin-based neoadjuvant chemotherapy should be offered to patients undergoing RNU or ureterectomy with HR UTUC, particularly in those patients whose post-operative eGFR is expected to be <60 mL/min/1.73m2 or those with other medical comorbidities that would preclude platinum-based chemotherapy in the post-operative setting.[https://pubmed.ncbi.nlm.nih.gov/37096584/]</span>''' | |||
***The strongly positive data from phase II trials, the established high-level evidence seen in bladder cancer trials, the consistent findings from pooled meta-analytic data, and the compelling clinical challenges imposed by post-RNU renal function on cis-platinum eligibility '''support the standard use of NAC regimens for HR UTUC.''' | |||
***Phase II trial of 30 patients with high-grade UTUC found that 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin was associated with a 14% pathological complete response rate.[https://pubmed.ncbi.nlm.nih.gov/31702432/] | |||
*** 2020 meta-analysis of 14 studies for NAC in UTUC found that the pooled pathologic complete response rate (≤ypT0N0M0) was 11% and pathologic partial response rate (≤ypT1N0M0) was 43%.[https://pubmed.ncbi.nlm.nih.gov/32798146/] | |||
**'''In the neoadjuvant setting, dosing regimens may be better tolerated, allowing more courses to be completed, and permitting patients to proceed to appropriate surgical intervention.''' | |||
*** A disadvantage of adjuvant chemotherapy is that many patients have baseline chronic kidney disease, which worsens after nephroureterectomy, rendering them ineligible to receive the full-dose cisplatin-based chemotherapy | |||
**'''Alternatives to cisplatin-based chemotherapy''' (i.e., immune checkpoint inhibitors, carboplatin, antibody drug conjugates, targeted FGFR therapies) '''are not recommended in the neoadjuvant setting''' (prior RNU or ureterectomy) outside of clinical trials | |||
====== Adjuvant ====== | |||
* '''Chemotherapy''' | |||
** '''<span style="color:#ff0000">Platinum-based adjuvant chemotherapy should be offered to patients with advanced pathological stage (pT2–T4 pN0–N3 M0 or pTany N1–3 M0) UTUC after RNU or ureterectomy who have not received neoadjuvant platinum-based therapy[https://pubmed.ncbi.nlm.nih.gov/37096584/]</span>''' | |||
*** '''Adjuvant platinum-based chemotherapy for select patients with UTUC post-RNU is a standard based on results from the randomized phase III POUT trial.''' | |||
**** '''<span style="color:#ff00ff">POUT</span>''' | |||
***** '''Population: 260 patients with histologically confirmed pT2-T4, N0-3, M0 or pTany, N+, MO UTUC''' | |||
******'''Pathological T stage: pT2 in 28%, pT3 in 66%, and pT4 in 6%''' | |||
******'''Nodal stage: N0 in 91%''', N1 in 6%, N2 in 3%, N3 in <1% | |||
******'''Site of tumour: renal pelvis in 35%, ureter in 34%, both renal pelvis and ureter in 30%''', and missing data in 1% | |||
******GFR: 30–49 in 36%, ≥50 in 64% | |||
***** '''Randomized to 4 cycles of gemcitabine-cisplatin''' (gemcitabine-carboplatin if GFR 30-49ml/min) '''or surveillance with subsequent chemotherapy, if required''' | |||
***** '''Primary outcome: disease-free survival''' | |||
***** Secondary endpoints included metastasis-free survival, overall survival, toxicity & quality of life | |||
***** '''Results''' | |||
****** '''Trial closed early as data met early stopping rule for efficacy''' | |||
****** Median follow-up: 30 months | |||
****** '''Disease-free survival improved by 21% at 3 years''' (71% chemotherapy vs. 46% surveillance; HR 0.45) | |||
****** '''Significantly improved metastasis-free survival; OS data not mature''' | |||
****** Toxicity: neutropenia, thrombocytopenia, nausea, febrile neutropenia, vomiting; QOL worse initially with chemotherapy, similar by 6 monthsA subgroup analysis demonstrated that outcomes for patients with lymph node involvement and those treated with carboplatin chemotherapy were worse than those without positive nodes or treated with cisplatin chemotherapy | |||
*******'''Carboplatin remains a reasonable choice for HR cisplatin-ineligible patients post-RNU if NAC was not given''' | |||
***** [https://pubmed.ncbi.nlm.nih.gov/32145825/ Birtle, Alison, et al.] "Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial." The Lancet (2020). | |||
**'''Immunotherapy''' | |||
***'''<span style="color:#ff0000">Adjuvant nivolumab therapy may be offered to patients who received neoadjuvant platinum-based chemotherapy (ypT2–T4 or ypN+) or who are ineligible for or refuse perioperative cisplatin (pT3, pT4a, or pN+)[https://pubmed.ncbi.nlm.nih.gov/37096584/]</span>''' | |||
****<span style="color:#ff00ff">'''CheckMate 274 (adjuvant nivolumab)'''</span> | |||
*****'''Population: 709 patients with high risk of recurrence after radical surgery for muscle-invasive urothelial carcinoma of the bladder, ureter, or renal pelvis, with or without neoadjuvant cisplatin-based therapy''' | |||
******'''High risk defined as''' | |||
*******'''Pathological stage pT3, pT4a, or pN+ and patient not eligible for or declined adjuvant cisplatin-based combination therapy for patients without previous neoadjuvant cisplatin-based chemotherapy''' | |||
*******'''Pathological stage ypT2 to ypT4a or pyN+ for patients who received neoadjuvant cisplatin''' | |||
******'''Enrollment of patients with upper tract urothelial carcinoma capped at approximately 20%''' | |||
*****'''Randomized 1:1 to nivolumab''' (240 mg intravenously) '''or placebo''' every 2 weeks for up to 1 year | |||
*****'''Outcomes:''' | |||
******'''Primary: disease-free survival''' | |||
*******Among all the patients (intention-to-treat population) | |||
*******Among patients with a tumor programmed death ligand 1 (PD-L1) expression level of ≥1% | |||
******Secondary: survival free from recurrence outside the urothelial tract, overall survival, and disease-specific survival | |||
*****'''Results''' | |||
******'''Median follow-up: ≈20 months''' | |||
******'''Primary outcome: disease-free survival''' | |||
*******'''Disease-free survival benefit: 10 months''' (21 months nivolumab vs. 11 months placebo) | |||
*******Absolute disease-free survival benefit at 6 months: | |||
*******All patients: 15% (75% adjuvant nivolumab vs. 60% placebo) | |||
*******PD-L1 patients (40% of all patients): 18% (74% adjuvant nivolumab vs. 56% placebo) | |||
*******'''In patients with upper tract urothelial carcinoma, hazard ratio in favour of placebo''' | |||
******Secondary outcomes: | |||
*******Distant metastasis-free survival improved with adjuvant nivolumab in both groups | |||
*******Overall survival and disease-specific survival not reported | |||
******Adverse events | |||
*******Most common adverse events in nivolumab group: pruritis (23%), fatigue (17%), and diarrhea (17%) | |||
*******Most common adverse events of grade 3 or higher in nivolumab group: elevated serum lipase (5%), elevated serum amylase (4%), diarrhea (1%), colitis (1%), and pneumonitis (1%) | |||
*******3/351 (1%) treatment-related deaths in nivolumab group, 2 from pneumonitis, 1 from bowel perforation | |||
*****[https://pubmed.ncbi.nlm.nih.gov/34077643/ Bajorin, Dean F., et al.] "Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma." ''New England Journal of Medicine'' 384.22 (2021): 2102-2114. | |||
****'''Adjuvant nivolumab approved for UTUC and urothelial carcinoma of the bladder in patients with advanced disease identified from post-surgical pathology findings''' | |||
*****'''Adjuvant platinum-chemotherapy over adjuvant nivolumab is recommended for eligible patients who did not receive NAC.''' | |||
***'''Scenarios for use of adjuvant nivolumab include:<span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/37096584/]</span>''' | |||
***#'''Patients with contraindications to platinum-based chemotherapy (e.g., poor renal function, performance status, sensorineural hearing loss, neuropathy or congestive heart failure, allergy)''' | |||
***#'''Patients with HR pathology after NAC''' | |||
***#'''Patients who refuse standard forms of adjuvant chemotherapy after appropriate counseling.''' | |||
===== Radiation ===== | |||
* Radical nephroureterectomy alone provides a high rate of local control; '''adjuvant radiation''' without chemotherapy for high-stage disease '''does not protect against a high rate of distant failure''' | |||
* Retrospective studies suggest that there may be a role for combined radiation-chemotherapy regimens in patients with advanced disease with adverse features | |||
====Special scenarios==== | ====Special scenarios==== | ||
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===== CIS limited to the region within the ureteral orifice ===== | ===== CIS limited to the region within the ureteral orifice ===== | ||
*Topical therapies such as BCG along with refluxing ureteral stenting that has been used for in cases of CIS near the ureterovesical junction | *Topical therapies such as BCG along with refluxing ureteral stenting that has been used for in cases of CIS near the ureterovesical junction | ||
*Transurethral resection of the transmural portion of the ureter for very distal tumors, as an extension of bladder resection procedures, when tumor is limited to the region inside the ureteral orifice and not beyond the bladder wall, thus anatomically managed as bladder cancer | |||
===== Watchful waiting or surveillance ===== | ===== Watchful waiting or surveillance ===== | ||
*May be offered to select patients with UTUC with | *May be offered to select patients with UTUC with (2): | ||
* | *#Significant comorbidities/competing risks of mortality | ||
* | *# Significant risk of End-Stage Renal Disease with any intervention resulting in dialysis. | ||
*Discussion of treatment related risks including perioperative mortality may lead to a shared decision to proceed with active surveillance (whereby periodic assessments such as imaging or limited endoscopic assessment are performed) or watchful waiting/expectant management, where interventions are limited to palliation or awaiting symptomatic progression – especially in those with very limited life expectancy. | *Discussion of treatment related risks including perioperative mortality may lead to a shared decision to proceed with active surveillance (whereby periodic assessments such as imaging or limited endoscopic assessment are performed) or watchful waiting/expectant management, where interventions are limited to palliation or awaiting symptomatic progression – especially in those with very limited life expectancy. | ||
**In such cases, patients and family should be counseled and prepared for disease-related events such as bleeding, obstruction, infection, and pain with options for palliation that may be limited. | **In such cases, patients and family should be counseled and prepared for disease-related events such as bleeding, obstruction, infection, and pain with options for palliation that may be limited. | ||
=== Advanced disease === | === Advanced disease === | ||
==== Clinical, regional node-positive (N+)==== | ==== Clinical, regional node-positive (N+)==== | ||
* '''Should initially be treated with systemic therapy.''' | * '''<span style="color:#ff0000">Should initially be treated with systemic therapy.''' | ||
*'''Consolidative RNU or ureterectomy with lymph-node dissection may be performed in those with a partial or complete response.''' | *'''<span style="color:#ff0000">Consolidative RNU or ureterectomy with lymph-node dissection may be performed in those with a partial or complete response.''' | ||
**Pooled data from comparative outcomes utilizing NAC in patients with clinically node positive (cN+) disease supports this approach. | **Pooled data from comparative outcomes utilizing NAC in patients with clinically node positive (cN+) disease supports this approach. | ||
====Distant metastatic disease (M+)==== | ====Distant metastatic disease (M+)==== | ||
* '''Systemic therapy and alternative approaches (i.e., radiotherapy with or without chemotherapy in selected cases) should be favored for inoperable or symptomatic patients with M+ UTUC''' | * '''Systemic therapy and alternative approaches (i.e., radiotherapy with or without chemotherapy in selected cases) should be favored for inoperable or symptomatic patients with M+ UTUC''' | ||
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**Formulating alternative care options should be approached with multi-disciplinary input with a focus on realistic goals of care such as providing means of local control for functional preservation (e.g., renal function) and palliation (e.g., bleeding, infection) | **Formulating alternative care options should be approached with multi-disciplinary input with a focus on realistic goals of care such as providing means of local control for functional preservation (e.g., renal function) and palliation (e.g., bleeding, infection) | ||
**Multi-modal approaches include combination of endoscopic management to maintain upper and lower tract function (e.g., stents, nephrostomies, ablation for bleeding and local control) in addition to systemic treatment options if available. Rarely, radiation, angioembolization, or percutaneous ablation for palliation of bleeding can be offered | **Multi-modal approaches include combination of endoscopic management to maintain upper and lower tract function (e.g., stents, nephrostomies, ablation for bleeding and local control) in addition to systemic treatment options if available. Rarely, radiation, angioembolization, or percutaneous ablation for palliation of bleeding can be offered | ||
== Prognosis == | == Prognosis == | ||
| Line 964: | Line 1,048: | ||
**#* '''CIS of the upper tract is associated with higher risk for disease progression''' (similar to bladder cancer) and a likelihood of future development of invasive urothelial cancers. | **#* '''CIS of the upper tract is associated with higher risk for disease progression''' (similar to bladder cancer) and a likelihood of future development of invasive urothelial cancers. | ||
**# '''Size''' | **# '''Size''' | ||
**#* Tumours > 3-4 cm may be associated with worse survival | **#* Tumours > 3-4 cm may be associated with worse survival and higher risk of bladder recurrence | ||
**# '''<span style="color:#ff0000">Location</span>''' | **# '''<span style="color:#ff0000">Location</span>''' | ||
**#* '''<span style="color:#ff0000">Renal pelvic tumours are usually more aggressive than ureteral tumours</span>''' | **#* '''<span style="color:#ff0000">Renal pelvic tumours are usually more aggressive than ureteral tumours</span>''' | ||
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===Oncologic Surveillance=== | ===Oncologic Surveillance=== | ||
*The primary aims of postoperative surveillance for UTUC are to identify | *The primary aims of postoperative surveillance for UTUC are to identify | ||
* | *#Urothelial recurrences | ||
* | *#De novo tumours of the urinary tract | ||
* | *#Regional/distant metastases at early stages when they may be amenable to treatment | ||
* '''Recurrence after''' | * '''Recurrence after''' | ||
**'''Nephron-sparing approaches''' | **'''Nephron-sparing approaches''' | ||
| Line 1,011: | Line 1,095: | ||
******Unclear how long bladder surveillance should continue for after 2 years | ******Unclear how long bladder surveillance should continue for after 2 years | ||
***** '''Given the high incidence of metachronous bladder involvement, routine bladder surveillance should be performed in patients with a history of UTUC''' | ***** '''Given the high incidence of metachronous bladder involvement, routine bladder surveillance should be performed in patients with a history of UTUC''' | ||
****Risk factors for intravesical recurrence: | ****Risk factors for intravesical recurrence: | ||
****#Male sex | ****#Male sex | ||
| Line 1,041: | Line 1,121: | ||
******Retroperitoneum or pelvis occurred in ≈5% | ******Retroperitoneum or pelvis occurred in ≈5% | ||
*****In patients with HG disease, LVI, or tumor multifocality, periodic imaging of the abdomen and pelvis is warranted, particularly for the first 2 years | *****In patients with HG disease, LVI, or tumor multifocality, periodic imaging of the abdomen and pelvis is warranted, particularly for the first 2 years | ||
****Port-site occur very infrequently, usually associated with inadvertent entry into the collecting system. | *****Port-site occur very infrequently, usually associated with inadvertent entry into the collecting system. | ||
****Distant metastases | ****Distant metastases | ||
*****Occurred following nephroureterectomy in 16% of patients. | *****Occurred following nephroureterectomy in 16% of patients. | ||
***** Median time to metastases | ***** Median time to metastases: 13-16 months. | ||
*****Location of metastases | *****Location of metastases | ||
******Lung metastasis (5%) | ******Lung metastasis (5%) | ||