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AUA: Upper Tract Urothelial Carcinoma (2023): Difference between revisions

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* Literature search up to January 2023
* Literature search up to January 2023
'''*****All of the information below is contained in the more comprehensive [[Upper Urinary Tract Urothelial Cancer|Upper Urinary Tract Urothelial Cancer Chapter Notes]]*****'''


== Background ==
== Background ==
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** '''<span style="color:#ff0000">Unfavorable</span>'''  
** '''<span style="color:#ff0000">Unfavorable</span>'''  
*** '''<span style="color:#ff0000">Tumor ablation (optional)</span>'''
*** '''<span style="color:#ff0000">Tumor ablation (optional)</span>'''
*** '''<span style="color:#ff0000">Radical nephroureterectomy or segmental ureterectomy</span>'''
*** '''<span style="color:#ff0000">Surgical removal (radical nephroureterectomy or segmental ureterectomy)</span>'''
** '''<span style="color:#ff0000">If low-risk and complete endoscopic ablation not feasible, chemoablation (in-situ tissue destruction) with mitomycin containing reverse thermal gel can be a treatment alternative</span>'''
** '''<span style="color:#ff0000">If low-risk and complete endoscopic ablation not feasible, chemoablation (in-situ tissue destruction) with mitomycin containing reverse thermal gel can be a treatment alternative</span>'''
* '''<span style="color:#ff0000">If high-risk</span>'''
* '''<span style="color:#ff0000">If high-risk</span>'''
** '''<span style="color:#ff0000">Favorable</span>'''
** '''<span style="color:#ff0000">Favorable</span>'''
*** '''<span style="color:#ff0000">Radical nephroureterectomy or segmental ureterectomy</span>'''
*** '''<span style="color:#ff0000">Surgical removal</span>'''  
*** '''<span style="color:#ff0000">Tumor ablation (optional)</span>'''
*** '''<span style="color:#ff0000">Tumor ablation (optional)</span>'''
**** '''<span style="color:#ff0000">Select patients who have low-volume tumors or cannot undergo RNU</span>'''
**** '''<span style="color:#ff0000">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">Radical nephroureterectomy or segmental ureterectomy</span>'''
*** '''<span style="color:#ff0000">Surgical removal</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>'''


=== Patient counseling ===
=== Patient counseling ===
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**'''<span style="color:#ff0000">If residual disease identified, repeat endoscopic assessment should occur within 3-month intervals until no evidence of upper tract disease is identified.</span>'''
**'''<span style="color:#ff0000">If residual disease identified, repeat endoscopic assessment should occur within 3-month intervals until no evidence of upper tract disease is identified.</span>'''
* '''In patients with LR UTUC with evidence of risk group progression (tumor size, focality, or grade) or when tumor ablation is not feasible,''' further endoscopic-assisted attempts are not recommended. '''surgical resection of all involved sites either by RNU or segmental resection of the ureter should be offered.'''
* '''In patients with LR UTUC with evidence of risk group progression (tumor size, focality, or grade) or when tumor ablation is not feasible,''' further endoscopic-assisted attempts are not recommended. '''surgical resection of all involved sites either by RNU or segmental resection of the ureter should be offered.'''
=== Surgical Resection ===
=== Surgical Removal ===


==== Indications ====
==== Indications ====
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===== Lymph node dissection =====
===== Lymph node dissection =====
* '''If HR UTUC, LND recommended'''
* '''<span style="color:#ff0000">If HR UTUC, LND recommended</span>'''
** 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
** There is sufficient non-randomized evidence to suggest an oncologic benefit to LND at the time of NU for patients with “HR” stratification by guidelines
** Sufficient non-randomized evidence to suggest an oncologic benefit to LND at the time of NU for patients with “HR” stratification by guidelines
** '''Recommended minimal templates in non-metastatic disease'''
** '''Recommended minimal templates in non-metastatic disease'''
*** '''Tumors in the pyelocaliceal system: lymph nodes of the ipsilateral great vessel extending from the renal hilum to at least the inferior mesenteric artery.'''  
*** '''Tumors in the pyelocaliceal system: lymph nodes of the ipsilateral great vessel extending from the renal hilum to at least the inferior mesenteric artery.'''  
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*** 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
*** 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
* '''If LR UTUC, LND optional'''
* '''<span style="color:#ff0000">If LR UTUC, LND optional</span>'''
**Limited evidence exists to support a beneficial role for LND at time of NU or ureterectomy among patients with LR UTUC
**Limited evidence exists to support a beneficial role for LND at time of NU or ureterectomy among patients with LR UTUC


==== Neoadjuvant/Adjuvant Chemotherapy and Immunotherapy ====
==== Neoadjuvant/Adjuvant Chemotherapy and Immunotherapy ====


===== Neoadjuvant 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 in eligible patients to reduce the risk of bladder recurrence.</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.
**Little data to support one intravesical chemotherapeutic over another.
***Many use gemcitabine over mitomycin due to risks of chemical peritonitis with extravesical extravasation of MMC
===== Systemic chemotherapy =====


* 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.
====== Neoadjuvant systemic chemotherapy ======
*'''<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.</span>'''
** The strongly positive data from these 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.
** The strongly positive data from these 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.
* 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.
* '''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.'''
* 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
* '''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 =====
====== Adjuvant systemic 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</span>'''
* Adjuvant intravesical chemotherapy
** '''Adjuvant platinum-based chemotherapy for select patients with UTUC post-RNU is a standard based on results from the randomized phase III POUT trial.'''
**'''In patients undergoing RNU or SU (including distal ureterectomy) for UTUC, a single dose of perioperative intravesical chemotherapy should be administered in eligible patients to reduce the risk of bladder recurrence.'''
*** Subjects in the adjuvant chemotherapy arm had improved DFS and  lower risk of metastases or death, compared with those on observation.
***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.
*** A 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
***Little data to support one intravesical chemotherapeutic over another.
**** '''Carboplatin remains a reasonable choice for HR cisplatin-ineligible patients post-RNU if NAC was not given'''
****Many use gemcitabine over mitomycin due to risks of chemical peritonitis with extravesical extravasation of MMC
*Adjuvant systemic chemotherapy
**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
*** Adjuvant platinum-based chemotherapy for select patients with UTUC post-RNU is a standard based on results from the randomized phase III POUT trial.
**** Subjects in the adjuvant chemotherapy arm had improved DFS and  lower risk of metastases or death, compared with those on observation.
**** A 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


===== Adjuvant immunotherapy =====
===== Adjuvant immunotherapy =====


* 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+)
* '''<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+)</span>'''
** CheckMate 274 evaluated adjuvant nivolumab following surgery in patients with HR non-metastatic urothelial carcinoma
** CheckMate 274 evaluated adjuvant nivolumab following surgery in patients with HR non-metastatic urothelial carcinoma
*** Majority of patients underwent radical cystectomy for bladder primaries, 20% of patients underwent surgery for UTUC
*** Majority of patients underwent radical cystectomy for bladder primaries, 20% of patients underwent surgery for UTUC
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*** Adjuvant nivolumab approved for UTUC and urothelial carcinoma of the bladder in patients with advanced disease identified from post-surgical pathology findings
*** 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:  
** Adjuvant platinum-chemotherapy over adjuvant nivolumab is recommended for eligible patients who did not receive NAC. Scenarios for use of adjuvant nivolumab include:  
*** 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 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 with HR pathology after NAC
*** Patients who refuse standard forms of adjuvant chemotherapy after appropriate counseling.
**# Patients who refuse standard forms of adjuvant chemotherapy after appropriate counseling.


=== Special scenarios ===
=== Special scenarios ===


==== Watchful waiting ====
==== Watchful waiting or surveillance ====


*Clinicians may offer watchful waiting or surveillance alone to select patients with UTUC with significant comorbidities, competing risks of mortality, or at significant risk of End-Stage Renal Disease (ESRD) with any intervention resulting in dialysis.
*May be offered to select patients with UTUC with  
**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.
**Significant comorbidities/competing risks of mortality
**Significant risk of End-Stage Renal Disease (ESRD) 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.  
**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.


==== CIS limited to the region within the ureteral orifice ====
==== CIS limited to the region within the ureteral orifice ====
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** Oncologic outcomes in the metastatic setting are strongly determined by response to systemic therapy, and surgical treatment has no demonstrable therapeutic efficacy for cytoreduction or as a single modality in this setting.
** Oncologic outcomes in the metastatic setting are strongly determined by response to systemic therapy, and surgical treatment has no demonstrable therapeutic efficacy for cytoreduction or as a single modality in this setting.


==== '''Unresectable UTUC''' ====
==== Unresectable UTUC ====
* Localized disease may be deemed unresectable or ineligible for extirpative surgical management due to significant medical comorbidities or other factors including refusal to accept surgical treatment (e.g., solitary kidney).
* Localized disease may be deemed unresectable or ineligible for extirpative surgical management due to significant medical comorbidities or other factors including refusal to accept surgical treatment (e.g., solitary kidney).
* Should be offered a clinical trial or best supportive care including palliative management (radiation, systemic approach, endoscopic, or ablative) for refractory symptoms such as hematuria.
* Should be offered a clinical trial or best supportive care including palliative management (radiation, systemic approach, endoscopic, or ablative) for refractory symptoms such as hematuria.
** 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
== Surveillance and Survivorship ==
== Surveillance and Survivorship ==


=== Post-Treatment Surveillance ===
=== Oncologic Surveillance ===


* '''See [https://www.auanet.org/images/Guidelines/Guideline%20Images/UTUC%202023/Table%206%20UTUC%20Word%20Version.jpg Table] from Original Guidelines'''
* '''See [https://www.auanet.org/images/Guidelines/Guideline%20Images/UTUC%202023/Table%206%20UTUC%20Word%20Version.jpg Table] from Original Guidelines'''
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* '''Low-risk patients managed with kidney sparing treatment'''  
* '''Low-risk patients managed with kidney sparing treatment'''  
** '''Cystoscopy and upper tract endoscopy within 1-3 months of treatment to confirm successful treatment.'''
** Cystoscopy and upper tract endoscopy within 1-3 months of treatment to confirm successful treatment.
**'''If successful treatment confirmed (no evidence of disease), perform'''
**If successful treatment confirmed (no evidence of disease), perform
***'''Cystoscopy of the bladder once again within the first year after treatment, then at least every 6-9 months for the first 2 years and then at least annually thereafter.'''
***Cystoscopy of the bladder once again within the first year after treatment, then at least every 6-9 months for the first 2 years and then at least annually thereafter.
***'''Upper tract endoscopy at 6 months and 1 year [after treatment].'''
***Upper tract endoscopy at 6 months and 1 year [after treatment].  
****Can be subsequently performed for any symptoms or significant findings on upper tract imaging.
****Can be subsequently performed for any symptoms or significant findings on upper tract imaging.
***'''Upper tract imaging should be performed at least every 6-9 months for first 2 years, then annually up to 5 years.'''
***Upper tract imaging should be performed at least every 6-9 months for first 2 years, then annually up to 5 years.
***'''Surveillance after 5 years in the absence of recurrence should be based on shared decision-making.'''
***Surveillance after 5 years in the absence of recurrence should be based on shared decision-making.
**Risk of distant metastasis with low-risk disease is low
**No distant metastatic evaluation since risk is low with low-risk disease
* '''High-risk patients managed with kidney sparing treatment'''  
* '''High-risk patients managed with kidney sparing treatment'''  
** '''Cystoscopy, upper tract endoscopy, and upper tract urine cytology within 1-3 months of treatment to confirm successful treatment.'''
** Cystoscopy, upper tract endoscopy, and upper tract urine cytology within 1-3 months of treatment to confirm successful treatment.
**'''If successful treatment confirmed (no evidence of disease), perform'''
**If successful treatment confirmed (no evidence of disease), perform
***'''Cystoscopy of the bladder and cytology at least every 3-6 months for the first 3 years and then every 6-12 months up to 5 years.'''
***Cystoscopy of the bladder and cytology at least every 3-6 months for the first 3 years and then every 6-12 months up to 5 years.
***'''Upper tract endoscopy should be performed at least at 6 months and 1 year [after treatment]'''
***Upper tract endoscopy should be performed at least at 6 months and 1 year [after treatment]
***'''Upper tract imaging and BMP should be performed every 3-6 months for 3 years, then every 6-12 months for 2 years, and then annually thereafter.'''
***Upper tract imaging and BMP should be performed every 3-6 months for 3 years, then every 6-12 months for 2 years, and then annually thereafter.
***'''Distant metastatic evaluation: Chest imaging (chest X-ray or CT) is recommended every 6-12 months to evaluate for intrathoracic metastasis up to 5 years following last diagnosis/treatment'''
***Distant metastatic evaluation: Chest imaging (chest X-ray or CT) is recommended every 6-12 months to evaluate for intrathoracic metastasis up to 5 years following last diagnosis/treatment
***'''Surveillance after 5 years in the absence of recurrence should be based on shared decision-making.'''
***Surveillance after 5 years in the absence of recurrence should be based on shared decision-making.
* '''If patient develops urothelial recurrence in the bladder or urethra or positive cytology following kidney sparing treatment for UTUC, evaluate for possible ipsilateral recurrence or development of new contralateral upper tract disease.'''
* '''If patient develops urothelial recurrence in the bladder or urethra or positive cytology following kidney sparing treatment for UTUC, evaluate for possible ipsilateral recurrence or development of new contralateral upper tract disease.'''


==== Surveillance after radical NU ====
==== Surveillance after radical nephroureterectomy ====


* Follow up after NU for patients with non-muscle invasive, node-negative UTUC should be largely focused on the risk of intravesical recurrence
* Intravesical recurrence
** Rates of intravesical recurrence after NU: ≈29%; median time to recurrence 6-22 months
**Rates of intravesical recurrence after nephroureterectomy: ≈29%
** Most recurrences occur within the first 2 years
*** Most recurrences occur within the first 2 years
*** Unclear how long bladder surveillance should continue for after 2 years
**** Unclear how long bladder surveillance should continue for after 2 years
**Risk factors for intravesical recurrence:
**Risk factors for intravesical recurrence:
***Male sex
**#Male sex
***Previous bladder cancer
**#Previous bladder cancer
***Preoperative CKD
**#Preoperative CKD
***Positive preoperative urinary cytology
**#Positive preoperative urinary cytology
***Ureteral tumor size
**#Ureteral tumor size
***Multifocality
**#Multifocality
***Invasive pathologic T-stage
**#Invasive pathologic T-stage
***Presence of necrosis
**#Presence of necrosis
***Laparoscopic approach
**#Laparoscopic approach
***Extravesical bladder cuff removal
**#Extravesical bladder cuff removal
***Positive surgical margins
**#Positive surgical margins
***Prior ureteroscopic biopsy
**#Prior ureteroscopic biopsy
**Given the substantial risk of local (bladder) recurrences within the first years following NU, risk adapted surveillance with cystoscopy and urine cytology at routine intervals is indicated to facilitate prompt detection of bladder recurrences.
**Given the substantial risk of local (bladder) recurrences within the first years following nephroureterectomy, risk adapted surveillance with cystoscopy and urine cytology at routine intervals is indicated to facilitate prompt detection of bladder recurrences.
* Risk of recurrence to the contralateral upper: ≈2%
* Contralateral recurrence
** Upper tract imaging should be performed with CT urogram, if possible.
**Risk of recurrence to the contralateral upper tract: ≈2%
*Locoregional, retroperitoneal, and distant metastases
*Locoregional, retroperitoneal, and distant metastases
**Risk factors for recurrence
**Risk factors
***Multifocality
***Multifocality
***Stage T3-4
***Stage T3-4
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***Brain
***Brain
****Rare following nephroureterectomy
****Rare following nephroureterectomy
****Patients undergoing follow-up for HR UTUC following NU with acute neurological signs or symptoms should undergo prompt neurologic evaluation with cross-sectional imaging of the brain and/or spine by CT or MRI
****Patients undergoing follow-up for HR UTUC following nephroureterectomy with acute neurological signs or symptoms should undergo prompt neurologic evaluation with cross-sectional imaging of the brain and/or spine by CT or MRI


* '''<pT2 N0/M0 managed with NU'''
* '''<pT2 N0/M0 managed with NU'''
** Cystoscopy and urine cytology within 3 months after surgery, then repeated based on pathologic grade.  
** Cystoscopy and urine cytology within 3 months after surgery, then repeated based on pathologic grade.  
***For LG this should repeated at least every six to nine months for the first two years and then at least annually thereafter.  
***For LG this should repeated at least every 5-9 months for the first 2 years and then at least annually thereafter.
***For HG, this should be repeated at least every three to six months for the first three years and then at least annually thereafter.  
***For HG, this should be repeated at least every 3-6 months for the first 3 years and then at least annually thereafter.
**Cross-sectional imaging of the abdomen and pelvis should be done within 6 months after surgery and then at least annually for a minimum of 5 years
**Cross-sectional imaging of the abdomen and pelvis should be done within 6 months after surgery and then at least annually for a minimum of 5 years
***Due to the metastasis risk and estimated 5% probability for contralateral disease
***Due to the metastasis risk and estimated 5% probability for contralateral disease
***Follow up after nephroureterectomy for patients with non-muscle invasive, node-negative UTUC should be largely focused on the risk of intravesical recurrence
**Surveillance after five years in the absence of recurrence should be encouraged and based on shared decision-making between the patient and clinician
**Surveillance after five years in the absence of recurrence should be encouraged and based on shared decision-making between the patient and clinician
* '''T2+ managed with NU'''
* '''T2+ managed with NU'''
** Cystoscopy with cytology at three months after surgery, then every three to six months for 3 years, and then annually thereafter.  
** Cystoscopy with cytology at 3 months after surgery, then every 3-6 months for 3 years, and then annually thereafter.
**Cross-sectional imaging of the abdomen and pelvis with multiphasic contrast-enhanced CT urography should be performed every three to six months for years one and two, every six months at year three, and annually thereafter to year five.  
**Cross-sectional imaging of the abdomen and pelvis with multiphasic contrast-enhanced CT urography should be performed every 3-6 months for years 1 and 2, every 6 months at year 3, and annually thereafter to year 5.
**Chest imaging, preferably with chest CT, every 6-12 months for the first 5 years.  
**Chest imaging, preferably with chest CT, every 6-12 months for the first 5 years.  
**Beyond five years after surgery in patients without recurrence, ongoing surveillance with cystoscopy and upper tract imaging may be continued on an annual basis according to principles of shared/informed decision-making
**Beyond five years after surgery in patients without recurrence, ongoing surveillance with cystoscopy and upper tract imaging may be continued on an annual basis according to principles of shared/informed decision-making
*'''Sequelae of NU'''
*'''Sequelae of nephroureterectomy'''
**'''Periodic laboratory assessment including serum creatinine level, eGFR, and urinalysis.'''  
**'''Repeat assessment of blood pressure, eGFR, and proteinuria should be performed soon after nephroureterectomy then again in 3-6 months to assess for development or progression of CKD.'''  
***With significant nephron mass loss, hyperfiltration can occur resulting in glomerular damage, exacerbation of proteinuria and progressive sclerosis with further decline in GFR.
***The long-term impact of renal dysfunction increases risks of osteoporosis, anemia, metabolic and cardiovascular disease, hospitalization and death.
***Effective treatment strategies are available to slow the progression of CKD and reduce cardiovascular risks, and therefore timely identification of progressive renal dysfunction and/or proteinuria can provide opportunity for medical intervention when indicated.
****Careful management of DM and HTN and avoidance of substantial weight gain may slow or prevent CKD progression and should be prioritized on a long-term basis
****Identifying modifiable risk factors including diabetes mellitus (DM), hypertension (HTN) and smoking is essential. Optimizing glycemic and blood pressure control, smoking cessation and minimizing risk of acute kidney injury (with avoidance of hypotension and nephrotoxic agents such as intravenous contrast or non-steroidal anti-inflammatory drugs) should reduce the degree of renal dysfunction in the perioperative period.
***'''In patients who develop progressive renal insufficiency or proteinuria should be referred to nephrology.'''
***'''In patients who develop progressive renal insufficiency or proteinuria should be referred to nephrology.'''
**Other laboratory evaluations (e.g., CBC, LDH, liver function tests, and alkaline phosphatase) may be obtained at the discretion of the clinician or if advanced disease is suspected.  
**Other laboratory evaluations (e.g., CBC, LDH, liver function tests, and alkaline phosphatase) may be obtained at the discretion of the clinician or if advanced disease is suspected.  
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=== Survivorship ===
=== Survivorship ===


* '''Repeat assessment of blood pressure, eGFR, and proteinuria should be performed soon after nephrectomy then again in 3-6 months to assess for development or progression of CKD.'''
**With significant nephron mass loss, hyperfiltration can occur resulting in glomerular damage, exacerbation of proteinuria and progressive sclerosis with further decline in GFR.
**The long-term impact of renal dysfunction increases risks of osteoporosis, anemia, metabolic and cardiovascular disease, hospitalization and death.
**Effective treatment strategies are available to slow the progression of CKD and reduce cardiovascular risks, and therefore timely identification of progressive renal dysfunction and/or proteinuria can provide opportunity for medical intervention when indicated.
***Careful management of DM and HTN and avoidance of substantial weight gain may slow or prevent CKD progression and should be prioritized on a long-term basis
***Identifying modifiable risk factors including diabetes mellitus (DM), hypertension (HTN) and smoking is essential. Optimizing glycemic and blood pressure control, smoking cessation and minimizing risk of acute kidney injury (with avoidance of hypotension and nephrotoxic agents such as intravenous contrast or non-steroidal anti-inflammatory drugs) should reduce the degree of renal dysfunction in the perioperative period.
* Discuss disease-related stresses and risk factors and encourage patients with urothelial cancer to adopt healthy lifestyle habits, including smoking cessation, exercise, and a healthy diet, to promote long-term health benefits and quality of life.
* Discuss disease-related stresses and risk factors and encourage patients with urothelial cancer to adopt healthy lifestyle habits, including smoking cessation, exercise, and a healthy diet, to promote long-term health benefits and quality of life.
**UTUC is associated with metabolic syndrome and obesity, with obesity adversely impacting disease-specific outcomes among patients undergoing RNU.
**UTUC is associated with metabolic syndrome and obesity, with obesity adversely impacting disease-specific outcomes among patients undergoing RNU.
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