Management of Localized and Locally Advanced Disease: Difference between revisions

 
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== Management of Localized (cT1-2) Renal Cell Carcinoma ==
== Management of Localized (cT1-2) Renal Cell Carcinoma ==


* '''<span style="color:#ff0000">Options:</span>'''
=== Established Treatment Options for Localized Prostate Cancer ===
*# '''<span style="color:#ff0000">Active surveillance (AS)/expectant management</span>'''
 
*# '''<span style="color:#ff0000">Thermal ablation (TA)</span>'''
==== <span style="color:#ff0000">Options (4):</span> ====
*# '''<span style="color:#ff0000">Partial nephrectomy (PN)</span>'''
# '''<span style="color:#ff0000">Active surveillance (AS)/expectant management</span>'''
*# '''<span style="color:#ff0000">Radical nephrectomy (RN)</span>'''
# '''<span style="color:#ff0000">Thermal ablation (TA)</span>'''
* Patient counseling
# '''<span style="color:#ff0000">Partial nephrectomy (PN)</span>'''
** Review the most common and serious urologic and non-urologic morbidities of each treatment pathway.
# '''<span style="color:#ff0000">Radical nephrectomy (RN)</span>'''
** Discuss potential effect of intervention on risk of chronic kidney disease (CKD), dialysis, and survival.
 
*** Patients with renal masses often have a high burden of CKD to begin with because of the shared risk factors with RCC and CKD, such as hypertension.
==== Patient counseling ====
*** '''Predictive factors for post-operative development of CKD or progression of pre-existing CKD (8):'''
* Review the most common and serious urologic and non-urologic morbidities of each treatment pathway.
***# '''Older age'''
* Discuss potential effect of intervention on risk of chronic kidney disease (CKD), dialysis, and survival.
***# '''Diabetes'''
** Patients with renal masses often have a high burden of CKD at baseline because of the shared risk factors with RCC and CKD, such as hypertension.
***# '''Hypertension'''
** '''Predictive factors for post-operative development of CKD or progression of pre-existing CKD (8):'''
***# '''Male sex'''
**# '''Older age'''
***# '''Obesity'''
**# '''Diabetes'''
***# '''Tobacco use'''
**# '''Hypertension'''
***# '''Larger tumour size'''
**# '''Male sex'''
***# '''Post-operative acute kidney injury'''
**# '''Obesity'''
*** 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.
**# '''Tobacco use'''
**# '''Larger tumour size'''
**# '''Post-operative acute kidney injury'''
** 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.


=== Active surveillance ===
=== Active surveillance ===


* '''Advantage'''
==== Advantages/Disadvantages ====
*'''Advantage'''
*# '''Least invasive'''
*# '''Least invasive'''
*#Renal function preservation (compared to radical nephrectomy)[https://pubmed.ncbi.nlm.nih.gov/25813449/]
*##No significant difference compared to ablation or partial nephrectomy
* '''Disadvantages'''
* '''Disadvantages'''
*# '''Patient anxiety'''
*# '''Patient anxiety'''
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*## '''Many small renal masses grow relatively slowly''' (median growth rate 0.12-0.34 cm/yr) '''and have a relatively <span style="color:#ff0000">low rate of metastasis (1-2% during 2-4 years of follow-up)</span>'''
*## '''Many small renal masses grow relatively slowly''' (median growth rate 0.12-0.34 cm/yr) '''and have a relatively <span style="color:#ff0000">low rate of metastasis (1-2% during 2-4 years of follow-up)</span>'''
*### Results may be an underestimate since many masses were not biopsied and there is limited follow-up.
*### Results may be an underestimate since many masses were not biopsied and there is limited follow-up.
* '''<span style="color:#ff0000">Indications</span>'''
 
** '''<span style="color:#ff0000">2021 AUA Localized RCC Guidelines</span>'''
==== Indications ====
*** '''<span style="color:#ff0000">Absolute (1):</span>'''
 
***# '''<span style="color:#ff0000">Risk of intervention/competing risks of death outweighs the potential benefits of intervention</span>'''
===== AUA =====
*** '''<span style="color:#ff0000">Relative (9):</span>'''
 
**** '''<span style="color:#ff0000">Tumour factors (2)</span>'''
* '''<span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/28479239/ 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer]</span>'''
***# '''<span style="color:#ff0000">Solid renal mass < 2cm</span>'''
** '''<span style="color:#ff0000">Absolute (1):</span>'''
***# '''<span style="color:#ff0000">Complex but predominantly cystic renal masses</span>'''
**# '''<span style="color:#ff0000">Risk of intervention/competing risks of death outweighs the potential benefits of intervention</span>'''
**** '''<span style="color:#ff0000">Patient factors (7)</span>'''
** '''<span style="color:#ff0000">Relative (9):</span>'''
***# '''<span style="color:#ff0000">Elderly</span>'''
*** '''<span style="color:#ff0000">Tumour factors (2)</span>'''
***# '''<span style="color:#ff0000">Life expectancy < 5 years</span>'''
**# '''<span style="color:#ff0000">Solid renal mass < 2cm</span>'''
***# '''<span style="color:#ff0000">High calculated comorbidities</span>'''
**# '''<span style="color:#ff0000">Complex but predominantly cystic renal masses</span>'''
***# '''<span style="color:#ff0000">Excessive perioperative risk</span>'''
*** '''<span style="color:#ff0000">Patient factors (7)</span>'''
***# '''<span style="color:#ff0000">Poor functional status</span>'''
**# '''<span style="color:#ff0000">Elderly</span>'''
***# '''<span style="color:#ff0000">Marginal renal function (≥CKD3b)</span>'''
**# '''<span style="color:#ff0000">Life expectancy < 5 years</span>'''
***# '''<span style="color:#ff0000">Patient preference</span>'''
**# '''<span style="color:#ff0000">High calculated comorbidities</span>'''
***#* For patients who prefer AS in whom the risk/benefit analysis for treatment is equivocal, consider renal mass biopsy (if the mass is solid or has solid components) for further oncologic risk stratification.
**# '''<span style="color:#ff0000">Excessive perioperative risk</span>'''
***#* For patients who prefer AS in whom the the anticipated benefits of intervention outweigh the risks of treatment, AS with potential for delayed intervention may be only pursued if the patient understands and is willing to accept the associated risks.
**# '''<span style="color:#ff0000">Poor functional status</span>'''
***#** In this setting, renal mass biopsy (if the mass is predominantly solid) is encouraged for additional risk stratification.
**# '''<span style="color:#ff0000">Marginal renal function (≥CKD3b)</span>'''
***#** If the patient continues to prefer AS, close clinical and cross-sectional imaging surveillance with periodic reassessment and counseling should be recommended.
**# '''<span style="color:#ff0000">Patient preference</span>'''
* '''<span style="color:#ff0000">Contraindications</span>'''
**#* For patients who prefer AS in whom the risk/benefit analysis for treatment is equivocal, consider renal mass biopsy (if the mass is solid or has solid components) for further oncologic risk stratification.
** '''In general, AS is not appropriate'''
**#* For patients who prefer AS in whom the the anticipated benefits of intervention outweigh the risks of treatment, AS with potential for delayed intervention may be only pursued if the patient understands and is willing to accept the associated risks.
*** '''Larger (>3-4 cm), poorly marginated, or nonhomogeneous solid renal lesions'''
**#** In this setting, renal mass biopsy (if the mass is predominantly solid) is encouraged for additional risk stratification.
*** '''Biopsy indicates a potentially aggressive RCC, except in patients with limited life expectancy'''
**#** If the patient continues to prefer AS, close clinical and cross-sectional imaging surveillance with periodic reassessment and counseling should be recommended.
** '''AS is also not advisable in younger, otherwise healthy, patients with small, solid tumors that have radiographic characteristics consistent with RCC'''
 
* '''<span style="color:#ff0000">Indications for intervention (treatment or AS intensity)</span>'''
===== NCCN =====
** '''<span style="color:#ff0000">2021 AUA (5)[https://www.auanet.org/guidelines/renal-cancer-renal-mass-and-localized-renal-cancer-guideline]:</span>'''
*'''<span style="color:#ff0000">2024 NCCN</span>'''
**# '''<span style="color:#ff0000">Tumour size >3cm</span>'''
**'''<span style="color:#ff0000">Option for clinical stage T1a tumors (partial nephrectomy is preferred treatment; other options are ablative techniques and radical nephrectomy (in select patients))</span>'''
**# '''<span style="color:#ff0000">Growth kinetics (>5mm/year)</span>'''
**'''<span style="color:#ff0000">In select patients with clinical stage T1b tumors (partial nephrectomy or radical nephrectomy are options, ablative technique (in select patients))</span>'''
**#* Caution if different imaging modalities are used due to normal variations in maximal tumor diameter and volume calculations; interreader variability may also be significant.
 
**# '''<span style="color:#ff0000">Stage progression</span>'''
==== Contraindications ====
**# '''<span style="color:#ff0000">Clinical changes in patient/tumour factors</span>''' (e.g. infiltrative on imaging, suspicion of advanced T stage)
* '''In general, AS is not appropriate'''
**# '''<span style="color:#ff0000">Additional biopsy results</span>''' (e.g. unfavourable histology)
** '''Larger (>3-4 cm), poorly marginated, or nonhomogeneous solid renal lesions'''
* '''<span style="color:#ff0000">Follow-up</span>'''
** '''Biopsy indicates a potentially aggressive RCC, except in patients with limited life expectancy'''
** '''Optimal regimen is unclear'''
* '''AS is also not advisable in younger, otherwise healthy, patients with small, solid tumors that have radiographic characteristics consistent with RCC'''
** '''Prior abdominal imaging should be evaluated to assess growth rate or changes in clinical stage'''
 
** '''<span style="color:#ff0000">2021 AUA[https://www.auanet.org/guidelines/renal-cancer-renal-mass-and-localized-renal-cancer-guideline]</span>'''
==== Indications for intervention (treatment or AS intensity) ====
*** '''<span style="color:#ff0000">Patients with no prior imaging should have surveillance imaging initially every 3 to 6 months</span>'''
* '''<span style="color:#ff0000">2021 AUA (5)[https://www.auanet.org/guidelines/renal-cancer-renal-mass-and-localized-renal-cancer-guideline]:</span>'''
*** Preferred modality is not well established, but initial imaging should preferably consist of contrast-enhanced cross-sectional imaging.
*# '''<span style="color:#ff0000">Tumour size >3cm</span>'''
*** '''Frequency and intensity are tailored to patient-risk,''' based on tumour size, tumor complexity, infiltrative appearance and median growth
*# '''<span style="color:#ff0000">Growth kinetics (>5mm/year)</span>'''
*** '''Chest x-ray is warranted annually or if intervention triggers are encountered or symptoms arise.'''
*#* Caution if different imaging modalities are used due to normal variations in maximal tumor diameter and volume calculations; interreader variability may also be significant.
*** Due to the imperfect nature of renal mass biopsy, patients with benign renal mass biopsy may warrant follow-up.
*# '''<span style="color:#ff0000">Stage progression</span>'''
*# '''<span style="color:#ff0000">Clinical changes in patient/tumour factors</span>''' (e.g. infiltrative on imaging, suspicion of advanced T stage)
*# '''<span style="color:#ff0000">Additional biopsy results</span>''' (e.g. unfavourable histology)
 
==== <span style="color:#ff0000">Follow-up</span> ====
* '''Optimal regimen is unclear'''
* '''Prior abdominal imaging should be evaluated to assess growth rate or changes in clinical stage'''
 
===== AUA =====
* '''<span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/28479239/ 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer]</span>'''
** '''<span style="color:#ff0000">Imaging</span>'''
***'''<span style="color:#ff0000">Renal mass: patients with no prior imaging should have surveillance imaging initially every 3 to 6 months</span>'''
****'''Frequency and intensity are tailored to patient-risk,''' based on tumour size, tumor complexity, infiltrative appearance and median growth
**** Preferred modality is not well established, but initial imaging should preferably consist of contrast-enhanced cross-sectional imaging.
*** '''<span style="color:#ff0000">Chest x-ray: warranted annually</span> or if intervention triggers are encountered or symptoms arise.'''
** Due to the imperfect nature of renal mass biopsy, patients with benign renal mass biopsy may warrant follow-up.


=== Expectant management (observation) ===
=== Expectant management (observation) ===
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=== Thermal ablation (TA) ===
=== Thermal ablation (TA) ===


* '''<span style="color:#ff0000">Options: radiofrequency ablation (RFA) and cryoablation</span>'''
==== <span style="color:#ff0000">Options (2):</span> ====
** '''Experience with renal cryosurgery predates that of RFA and has been more extensive'''
# '''<span style="color:#ff0000">Radiofrequency ablation (RFA)</span>'''  
** No randomized trials directly compare cryoablation to RFA
#'''<span style="color:#ff0000">Cryoablation</span>'''
** Meta-analyses have shown no significant differences between cryoablation and RFA in outcomes as defined by complications, metastatic progression, or cancer-specific survival.
#*'''Experience with renal cryosurgery predates that of RFA and has been more extensive'''
* '''<span style="color:#ff0000">Advantages (2):</span>'''
#* No randomized trials directly compare cryoablation to RFA
#* Meta-analyses have shown no significant differences between cryoablation and RFA in outcomes as defined by complications, metastatic progression, or cancer-specific survival.
 
==== Advantages/Disadvantages ====
*'''<span style="color:#ff0000">Advantages (2):</span>'''
*# '''Low morbidity'''
*# '''Low morbidity'''
*#* In the Agency for Healthcare Research and Quality (AHRQ) analysis, TA had the most favorable perioperative outcome profile and a similar low risk of harms when compared to other strategies
*#* In the Agency for Healthcare Research and Quality (AHRQ) analysis, TA had the most favorable perioperative outcome profile and a similar low risk of harms when compared to other strategies
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*#*** 26% of RFA and 7% of cryoablation patients did not undergo biopsy
*#*** 26% of RFA and 7% of cryoablation patients did not undergo biopsy
*#*** 3-year local recurrence-free survival rates were 98% for partial nephrectomy, RFA, and cryoablation.
*#*** 3-year local recurrence-free survival rates were 98% for partial nephrectomy, RFA, and cryoablation.
*#**** Thompson, R. Houston, et al. "Comparison of partial nephrectomy and percutaneous ablation for cT1 renal masses." ''European urology'' 67.2 (2015): 252-259.
*#** [https://pubmed.ncbi.nlm.nih.gov/25108580/ Thompson, R. Houston, et al. "Comparison of partial nephrectomy and percutaneous ablation for cT1 renal masses." ''European urology'' 67.2 (2015): 252-259.]
*#* Reported rates of local recurrence after TA may represent underestimates because ≈20% of small renal masses are benign rather than RCC, and a pretreatment biopsy has not always been performed.
*#* Reported rates of local recurrence after TA may represent underestimates because ≈20% of small renal masses are benign rather than RCC, and a pretreatment biopsy has not always been performed.
* '''<span style="color:#ff0000">Indications</span>'''
 
==== <span style="color:#ff0000">Indications</span> ====
* '''<span style="color:#ff0000">Alternative approach for management of cT1a solid renal masses <3cm</span>'''
** '''Current technology does not allow for reliable treatment of lesions >4.0 cm, and success rates appear to be highest for tumors <2.5-3.0 cm'''
* '''Relative (4):'''
*# '''Advanced age'''
*# '''Significant comorbidities'''
*# '''Local recurrence after previous nephron-sparing surgery'''
*# '''Hereditary renal cancer who present with multifocal lesions for which multiple PNs might be cumbersome'''
* '''<span style="color:#ff0000">2021 AUA[https://www.auanet.org/guidelines/renal-cancer-renal-mass-and-localized-renal-cancer-guideline]</span>'''
** '''<span style="color:#ff0000">Alternative approach for management of cT1a solid renal masses <3cm</span>'''
** '''<span style="color:#ff0000">Alternative approach for management of cT1a solid renal masses <3cm</span>'''
*** '''Current technology does not allow for reliable treatment of lesions >4.0 cm, and success rates appear to be highest for tumors <2.5-3.0 cm'''
*** Patients should be informed about the increased risk of tumor persistence or local recurrence after primary TA, compared to surgical excision, which may be treated with repeat ablation.
** '''Relative (4):'''
***PN seems preferred over TA for cT1a: "PN should be prioritized in the management of patients with clinical T1a renal mass".
**# '''Advanced age'''
 
**# '''Significant comorbidities'''
==== Contraindications ====
**# '''Local recurrence after previous nephron-sparing surgery'''
* '''Absolute'''
**# '''Hereditary renal cancer who present with multifocal lesions for which multiple PNs might be cumbersome'''
** '''Inaccessible tumour'''
** '''<span style="color:#ff0000">2021 AUA[https://www.auanet.org/guidelines/renal-cancer-renal-mass-and-localized-renal-cancer-guideline]</span>'''
** Large tumour
*** '''<span style="color:#ff0000">Alternative approach for management of cT1a solid renal masses <3cm</span>'''
* '''Relative'''
**** PN seems preferred over TA for cT1a: "PN should be prioritized in the management of patients with clinical T1a renal mass".
** Completely intrarenal lesions or those immediately adjacent to the sinus or hilum are more difficult to treat effectively by TA
* '''Contraindications'''
 
** '''Absolute'''
==== Technology ====
*** '''Inaccessible tumour'''
* '''RFA'''
*** Large tumour
** Utilizes high frequency alternating current (460-500 kHz) to induce ion agitation and frictional heating in adjacent tissue
** '''Relative'''
*** Can be achieved through 2 types of radiofrequency generator systems:
*** Completely intrarenal lesions or those immediately adjacent to the sinus or hilum are more difficult to treat effectively by TA
***# Temperature-based system: drives the current to reach a target temperature
* '''Technology'''
***# Impedance-based systems: continue ablation until a predetermined impedance level is reached.
** '''RFA'''
* '''Cryoablation'''
*** Utilizes high frequency alternating current (460-500 kHz) to induce ion agitation and frictional heating in adjacent tissue
** Generates lethal temperatures below -20 to -40 °C, resulting in coagulative tissue necrosis
**** Can be achieved through 2 types of radiofrequency generator systems:
** '''Volume of lethal temperature generated during cryoablation is regulated by (4):'''
****# Temperature-based system: drives the current to reach a target temperature
**# '''Duration of freezing'''
****# Impedance-based systems: continue ablation until a predetermined impedance level is reached.
**# '''Number of freeze cycles'''
*** '''Cryoablation'''
**#* '''<span style="color:#ff0000">Double freeze results in larger volumes of renal tissue necrosis, compared to single freeze</span>'''
**** Generates lethal temperatures below -20 to -40 °C, resulting in coagulative tissue necrosis
**# '''Size and number of cryoprobes'''
**** '''Volume of lethal temperature generated during cryoablation is regulated by (4):'''
**# '''Local tissue interactions'''
****# '''Duration of freezing'''
** '''<span style="color:#ff0000">Complete treatment of a tumour requires that the iceball extend beyond the tumor</span>''' because the peripheral leading edge of the iceball is at sub-lethal temperatures
****# '''Number of freeze cycles'''
*** Lethal temperatures are reached approximately 5 mm from the periphery of the iceball; '''<span style="color:#ff0000">the ice-ball is usually extended ≈1 cm beyond the edge of the tumor</span>'''
****#* '''<span style="color:#ff0000">Double freeze results in larger volumes of renal tissue necrosis, compared to single freeze</span>'''
*'''Both radiofrequency ablation and cryoablation may be offered as options[https://pubmed.ncbi.nlm.nih.gov/28479239/]'''
****# '''Size and number of cryoprobes'''
*Other new technologies, such as high-intensity focused ultrasound and image-guided radiosurgical treatments (SBRT), are under development and may allow extracorporeal treatment of small renal tumors in the future
****# '''Local tissue interactions'''
 
**** '''<span style="color:#ff0000">Complete treatment of a tumour requires that the iceball extend beyond the tumor</span>''' because the peripheral leading edge of the iceball is at sub-lethal temperatures
==== Technique ====
***** Lethal temperatures are reached approximately 5 mm from the periphery of the iceball; '''<span style="color:#ff0000">the ice-ball is usually extended ≈1 cm beyond the edge of the tumor</span>'''
* TA for cystic lesions requires further investigation.
* '''Technique'''
* '''<span style="color:#ff0000">Biopsy should be performed prior to (preferred) or at the time of ablation</span>''' to provide pathologic diagnosis and guide subsequent surveillance.'''[https://pubmed.ncbi.nlm.nih.gov/28479239/]'''
** TA for cystic lesions requires further investigation.
* Percutaneous approach is preferred over a surgical approach whenever feasible to minimize morbidity.
** '''<span style="color:#ff0000">A renal mass biopsy should be performed prior to ablation</span>''' to provide pathologic diagnosis and guide subsequent surveillance
** Percutaneous displacement techniques such as the use of fluid (hydro-dissection), carbon dioxide, or spacer balloons frequently enable separation of adjacent structures from the anticipated zone of ablation, rendering many cases suitable for percutaneous TA.
** Percutaneous approach is preferred over a surgical approach whenever feasible to minimize morbidity.
** A laparoscopic approach is seldom needed except for occasional cases in which adhesions prevent displacement of adjacent structures or when the collecting system is at risk for serious injury even with thermo-protective maneuvers such as pyeloperfusion.
*** Percutaneous displacement techniques such as the use of fluid (hydro-dissection), carbon dioxide, or spacer balloons frequently enable separation of adjacent structures from the anticipated zone of ablation, rendering many cases suitable for percutaneous TA.
 
*** A laparoscopic approach is seldom needed except for occasional cases in which adhesions prevent displacement of adjacent structures or when the collecting system is at risk for serious injury even with thermo-protective maneuvers such as pyeloperfusion.
==== Complications ====
* '''<span style="color:#ff0000">Complications</span>'''
* '''Cryoablation:'''
** '''Cryoablation:'''
*# '''Renal fracture'''
**# '''Renal fracture'''
*#* Higher risk when treating tumours >3cm
**#* Higher risk when treating tumours >3cm
*# '''Hemorrhage'''
**# '''Hemorrhage'''
*# '''Adjacent organ injury'''
**# '''Adjacent organ injury'''
*# '''Ileus'''
**# '''Ileus'''
*# '''Wound infection'''
**# '''Wound infection'''
* '''RFA (uncommon):'''
** '''RFA (uncommon):'''
*# '''Acute renal failure'''
**# '''Acute renal failure'''
*# '''Stricture of the ureteropelvic junction'''
**# '''Stricture of the ureteropelvic junction'''
*# '''Necrotizing pancreatitis'''
**# '''Necrotizing pancreatitis'''
*# '''Lumbar radiculopathy'''
**# '''Lumbar radiculopathy'''
 
* '''<span style="color:#ff0000">Post-treatment imaging</span>'''
==== Post-treatment imaging ====
** Immediate post-procedural imaging of the ablated tumor generally shows the treatment bed to be larger than the pre-treatment tumor size for RFA due to ablation of a peripheral margin of normal tissue, and for cryoablation due to extension of the iceball beyond the original tumor margin.
* Immediate post-procedural imaging of the ablated tumor generally shows the treatment bed to be larger than the pre-treatment tumor size for RFA due to ablation of a peripheral margin of normal tissue, and for cryoablation due to extension of the iceball beyond the original tumor margin.
** '''<span style="color:#ff0000">Renal tumours successfully treated with</span>'''
* '''<span style="color:#ff0000">Renal tumours successfully treated with</span>'''
*** '''<span style="color:#ff0000">RFA demonstrate no contrast enhancement. However, they do not regress significantly in size.</span>'''
** '''<span style="color:#ff0000">RFA demonstrate no contrast enhancement. However, they do not regress significantly in size.</span>'''
**** '''Residual enhancement is considered suggestive of residual or recurrent disease'''
*** '''Residual enhancement is considered suggestive of residual or recurrent disease'''
*** '''<span style="color:#ff0000">Cryoablation may demonstrate reduction in size or complete resolution or scar formation</span>'''
** '''<span style="color:#ff0000">Cryoablation may demonstrate reduction in size or complete resolution or scar formation</span>'''
** On MRI, the imaging hallmark of successful renal tumor ablation is lack of tumor enhancement with gadolinium-enhanced imaging.
* On MRI, the imaging hallmark of successful renal tumor ablation is lack of tumor enhancement with gadolinium-enhanced imaging.
** Rim enhancement, believed to represent reactive change, may occasionally be seen at early postprocedural MR scanning after RFA or cryoablation, which later resolves.
* Rim enhancement, believed to represent reactive change, may occasionally be seen at early postprocedural MR scanning after RFA or cryoablation, which later resolves.
* '''<span style="color:#ff0000">Recurrence following treatment</span>'''
 
** '''Diagnosis of local recurrence after TA can be challenging''' because evolving fibrosis within the tumor bed can be difficult to differentiate from residual cancer.
==== Recurrence following treatment ====
** '''<span style="color:#ff0000">Findings suggestive of local recurrence (5):</span>'''
* '''Diagnosis of local recurrence after TA can be challenging''' because evolving fibrosis within the tumor bed can be difficult to differentiate from residual cancer.
**# '''<span style="color:#ff0000">Enhancement within the tumor bed beyond 6 months</span>'''
* '''<span style="color:#ff0000">Findings suggestive of local recurrence (5):</span>'''
**# '''<span style="color:#ff0000">Progressive increase in size of an ablated neoplasm</span>'''
*# '''<span style="color:#ff0000">Enhancement within the tumor bed beyond 6 months</span>'''
**# '''<span style="color:#ff0000">New nodularity in or around the treated zone</span>'''
*# '''<span style="color:#ff0000">Progressive increase in size of an ablated neoplasm</span>'''
**# '''<span style="color:#ff0000">Failure of the treated lesion to regress over time</span>'''
*# '''<span style="color:#ff0000">New nodularity in or around the treated zone</span>'''
**# '''<span style="color:#ff0000">Satellite or port site lesions</span>'''
*# '''<span style="color:#ff0000">Failure of the treated lesion to regress over time</span>'''
** '''<span style="color:#ff0000">Most local recurrences can be salvaged with repeat ablation</span>'''
*# '''<span style="color:#ff0000">Satellite or port site lesions</span>'''
*** Some patients with progressive disease eventually require conventional surgery.
* '''<span style="color:#ff0000">Most local recurrences can be salvaged with repeat ablation</span>'''
**** PN and minimally invasive approaches are occasionally precluded in this setting because of the extensive fibrotic reaction induced by TA, necessitating RN.
** Some patients with progressive disease eventually require conventional surgery.
* Other new technologies, such as high-intensity focused ultrasound and image-guided radiosurgical treatments (SBRT), are under development and may allow extracorporeal treatment of small renal tumors in the future
*** PN and minimally invasive approaches are occasionally precluded in this setting because of the extensive fibrotic reaction induced by TA, necessitating RN.


=== Partial nephrectomy (PN) ===
=== Partial nephrectomy (PN) ===


* '''<span style="color:#ff0000">Advantage (1):</span>'''
==== Advantages/Disadvantages ====
*'''<span style="color:#ff0000">Advantage (1):</span>'''
*# '''<span style="color:#ff0000">Preserved renal function compared to RN</span>'''
*# '''<span style="color:#ff0000">Preserved renal function compared to RN</span>'''
*#* '''<span style="color:#ff0000">The number of preserved nephrons is the primary factor determining renal function after PN</span>'''
*#** '''<span style="color:#ff0000">Ischemic injury plays a secondary role.</span>'''
*#*** '''<span style="color:#ff0000">As long as the warm ischemic interval is limited (<25 minutes) or hypothermia is applied, most preserved nephrons will recover their function</span>'''
*#**** Recovery from hypothermia is more consistent and reliable with intervals up to 60-90 minutes being well tolerated. Nevertheless, even with hypothermia it is best to avoid truly prolonged durations of ischemia
* '''<span style="color:#ff0000">Disadvantages</span>'''
* '''<span style="color:#ff0000">Disadvantages</span>'''
*# '''<span style="color:#ff0000">Higher risk of blood transfusions and urologic complications (e.g. urine leak) than TA or RN</span>'''
*# '''<span style="color:#ff0000">Higher risk of blood transfusions and urologic complications (e.g. urine leak) than TA or RN</span>'''
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*#*** '''<span style="color:#ff0000">A 24-hour urinary protein measurement should be obtained yearly in patients with a solitary remnant kidney to screen for hyperfiltration nephropathy</span>'''
*#*** '''<span style="color:#ff0000">A 24-hour urinary protein measurement should be obtained yearly in patients with a solitary remnant kidney to screen for hyperfiltration nephropathy</span>'''
*#** '''<span style="color:#ff0000">Efforts to prevent or to ameliorate the damaging effects of hyperfiltration</span>''' have focused on dietary and pharmacologic interventions, primarily the use of '''<span style="color:#ff0000">ACE-inhibitors combined with a low-protein diet</span>'''
*#** '''<span style="color:#ff0000">Efforts to prevent or to ameliorate the damaging effects of hyperfiltration</span>''' have focused on dietary and pharmacologic interventions, primarily the use of '''<span style="color:#ff0000">ACE-inhibitors combined with a low-protein diet</span>'''
* '''<span style="color:#ff0000">Indications</span>'''
 
** '''<span style="color:#ff0000">2021 AUA</span>'''
==== Indications ====
*** '''<span style="color:#ff0000">Absolute (3):</span>'''
 
***# '''<span style="color:#ff0000">Anatomic or functionally solitary kidney</span>'''
===== AUA =====
***# '''<span style="color:#ff0000">Bilateral tumors</span>'''
*'''<span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/28479239/ 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer]</span>'''
***# '''<span style="color:#ff0000">Known familial RCC syndrome</span>'''
** '''<span style="color:#ff0000">Absolute (3):</span>'''
*** '''<span style="color:#ff0000">Relative (4):</span>'''
**# '''<span style="color:#ff0000">Anatomic or functionally solitary kidney</span>'''
***# '''<span style="color:#ff0000">cT1a renal masses (preferred over TA and RN)</span>''', not managed with active surveillance
**# '''<span style="color:#ff0000">Bilateral tumors</span>'''
***# '''<span style="color:#ff0000">Pre-existing CKD</span>'''
**# '''<span style="color:#ff0000">Known familial RCC syndrome</span>'''
***# '''<span style="color:#ff0000">Pre-existing proteinuria</span>'''
** '''<span style="color:#ff0000">Relative (4):</span>'''
***# '''<span style="color:#ff0000">Young age</span>'''
**# '''<span style="color:#ff0000">cT1a renal masses (preferred over TA and RN)</span>''', not managed with active surveillance
***# '''<span style="color:#ff0000">Multifocal masses</span>'''
**# '''<span style="color:#ff0000">Pre-existing CKD</span>'''
***# '''<span style="color:#ff0000">Comorbidities that are likely to impact future renal function, including (4):</span>'''
**# '''<span style="color:#ff0000">Pre-existing proteinuria</span>'''
***## '''<span style="color:#ff0000">Moderate to severe hypertension</span>'''
**# '''<span style="color:#ff0000">Young age</span>'''
***## '''<span style="color:#ff0000">Diabetes mellitus</span>'''
**# '''<span style="color:#ff0000">Multifocal masses</span>'''
***## '''<span style="color:#ff0000">Recurrent urolithiasis</span>'''
**# '''<span style="color:#ff0000">Comorbidities that are likely to impact future renal function, including (4):</span>'''
***## '''<span style="color:#ff0000">Morbid obesity</span>'''
**## '''<span style="color:#ff0000">Moderate to severe hypertension</span>'''
* '''<span style="color:#ff0000">Approach</span>'''
**## '''<span style="color:#ff0000">Diabetes mellitus</span>'''
** Can be done via open/laparoscopic/robotic approach
**## '''<span style="color:#ff0000">Recurrent urolithiasis</span>'''
*** Pure or robot-assisted laparoscopic PN should be done by experienced surgeons
**## '''<span style="color:#ff0000">Morbid obesity</span>'''
* Technique
 
** The extent of normal parenchyma removed should be determined by surgeon discretion taking into account the clinical situation, tumor characteristics including growth pattern, and interface with normal tissue.
==== Approach ====
*** Traditional PN is sharp excision with intentional removal of a modest rim of normal adjacent parenchyma
* Can be done via open/laparoscopic/robotic approach
**** The concept of tumor enucleation (or blunt excision of a tumor with minimal margin during nephron-sparing surgery) originated in the familial RCC population as a technique to preserve renal parenchyma in patients with multiple tumors requiring multiple surgeries over a lifetime.'''<span style="color:#ff0000">To optimize parenchymal mass preservation, tumor enucleation should be considered in patients with:</span>'''
** Pure or robot-assisted laparoscopic PN should be done by experienced surgeons
****# '''<span style="color:#ff0000">Familial RCC syndromes</span>'''
*A minimally invasive approach should be considered when it would not compromise oncologic, functional, and perioperative outcomes.[https://pubmed.ncbi.nlm.nih.gov/28479239/]
****#* '''Aggressive RCC syndromes, such as HLRCC, should be best managed with wide margin PN or RN.'''
*See [[Open Kidney Surgery|Open Kidney Surgery Chapter Notes]]
****# '''<span style="color:#ff0000">Multifocal disease</span>'''
*See [[Robotic Partial Nephrectomy|Robotic Partial Nephrectomy Chapter Notes]]
****# '''<span style="color:#ff0000">Severe CKD</span>'''
 
**** '''<span style="color:#ff0000">Margin width is not important as long as final margins are negative.</span>'''
==== Technique ====
***** '''While positive surgical margin during PN has not definitively been shown to adversely affect survival outcomes''' (recurrence-free, metastasis-free, cancer-specific, or overall survival'''), a negative surgical margin is always the goal; close surveillance is recommended in patients with a positive surgical margin'''
* '''Renal function can be optimized by (2):'''
****** Cohort study of 1,344 PN patients from MSK found that compared to negative margins, positive margins was not associated with worse recurrence-free or metastasis-free survival. J Urol 2008.
*#'''Optimizing nephron mass preservation'''
****** Multi-centre cohort study of 775 patients from Europe found that compared to negative margins, positive margins was not associated with worse recurrence-free, cancer-specific, or overall-survival. Eur Urol 2010.
*##'''<span style="color:#ff0000">The number of preserved nephrons is the primary factor determining renal function after PN</span>'''
***** Management of positive surgical margins after PN or tumor enucleation
*#'''Avoiding prolonged ischemia'''
****** Controversial
*##'''<span style="color:#ff0000">Ischemic injury plays a secondary role.</span>'''
****** A variety of factors should be taken into account during counseling including the extent of the margin (microscopic versus extensive), tumor histology and grade, and other indicators of tumor biology such as locally invasive phenotype.
*##* '''<span style="color:#ff0000">As long as the warm ischemic interval is limited (<25 minutes) or hypothermia is applied, most preserved nephrons will recover their function</span>'''
***** PN in patients with absolute indications should focus on preservation of renal parenchymal volume and functional nephrons with margin width being a less relevant consideration
*##** Recovery from hypothermia is more consistent and reliable with intervals up to 60-90 minutes being well tolerated. Nevertheless, even with hypothermia it is best to avoid truly prolonged durations of ischemia
* '''<span style="color:#ff0000">Local recurrence in the remnant kidney after PN for RCC</span>'''
*'''The extent of normal parenchyma removed should be determined by surgeon discretion taking into account the clinical situation, tumor characteristics including growth pattern, and interface with normal tissue.'''
** Occurs in 0-3% of patients
** Traditional PN is sharp excision with intentional removal of a modest rim of normal adjacent parenchyma
** '''Main risk factor is advanced T stage'''
**Tumor enucleation refers to blunt excision of a tumor with minimal margin during nephron-sparing surgery
** '''<span style="color:#ff0000">Most ipsilateral recurrences are distant from the tumor bed</span>''' and are therefore likely a result of unrecognized tumor multicentricity or de novo occurrence rather than true treatment failure
*** Originated in the familial RCC population as a technique to preserve renal parenchyma in patients with multiple tumors requiring multiple surgeries over a lifetime.
***'''<span style="color:#ff0000">To optimize parenchymal mass preservation, tumor enucleation should be considered in patients with:[https://pubmed.ncbi.nlm.nih.gov/28479239/]</span>'''
***# '''<span style="color:#ff0000">Familial RCC syndromes</span>'''
***#* '''Aggressive RCC syndromes, such as HLRCC, should be best managed with wide margin PN or RN.'''
***# '''<span style="color:#ff0000">Multifocal disease</span>'''
***# '''<span style="color:#ff0000">Severe CKD</span>'''
** '''<span style="color:#ff0000">Margin</span>'''
***'''<span style="color:#ff0000">Negative margin should be prioritized</span>'''
****While positive surgical margin during PN has not definitively been shown to adversely affect survival outcomes (recurrence-free, metastasis-free, cancer-specific, or overall survival), a negative surgical margin is always the goal
*****Cohort study of 1,344 PN patients from MSK found that compared to negative margins, positive margins was not associated with worse recurrence-free or metastasis-free survival. J Urol 2008.
***** Multi-centre cohort study of 775 patients from Europe found that compared to negative margins, positive margins was not associated with worse recurrence-free, cancer-specific, or overall-survival. Eur Urol 2010.
****'''<span style="color:#ff0000">Margin width is not important as long as final margins are negative.</span>'''
*** '''Management of positive surgical margins after PN or tumor enucleation'''
**** A variety of factors should be taken into account during counseling including the extent of the margin (microscopic versus extensive), tumor histology and grade, and other indicators of tumor biology such as locally invasive phenotype.
****'''In general, close surveillance is recommended in patients with a positive surgical margin'''
*** PN in patients with absolute indications should focus on preservation of renal parenchymal volume and functional nephrons with margin width being a less relevant consideration
 
==== Local recurrence in the remnant kidney after PN for RCC ====
* Occurs in 0-3% of patients
* '''Main risk factor is advanced T stage'''
* '''<span style="color:#ff0000">Most ipsilateral recurrences are distant from the tumor bed</span>''' and are therefore likely a result of unrecognized tumor multicentricity or de novo occurrence rather than true treatment failure
*Local recurrence rate after partial nephrectomy for pT1 with[https://link.springer.com/article/10.1007/s00345-022-04016-0]
**Negative margin: 0–1.5%
**Positive margin: 0-9%


=== Radical nephrectomy (RN) ===
=== Radical nephrectomy (RN) ===


* '''Advantages'''
==== Advantages/Disadvantages ====
*'''Advantages'''
*# '''Favorable perioperative outcomes compared to PN'''
*# '''Favorable perioperative outcomes compared to PN'''
*#* May reflect the high proportion of RN performed via the laparoscopic approach
*#* May reflect the high proportion of RN performed via the laparoscopic approach
Line 245: Line 300:
*** While these changes in GFR may be clinically insignificant in patients with a normal contralateral kidney, they warrant consideration in certain patients
*** While these changes in GFR may be clinically insignificant in patients with a normal contralateral kidney, they warrant consideration in certain patients
*** '''In general, median loss of global renal function with PN is ≈10%, while RN is typically associated with ≈35-40% loss of global function,''' although this can vary substantially for RN based on uneven split renal function, and for PN based on tumor complexity
*** '''In general, median loss of global renal function with PN is ≈10%, while RN is typically associated with ≈35-40% loss of global function,''' although this can vary substantially for RN based on uneven split renal function, and for PN based on tumor complexity
* '''<span style="color:#ff0000">Indications</span>'''
** '''<span style="color:#ff0000">2021 AUA (2)[https://www.auanet.org/guidelines/renal-cancer-renal-mass-and-localized-renal-cancer-guideline]:</span>'''
**# '''<span style="color:#ff0000">Increased oncologic potential is suggested</span>''' by tumor size, biopsy, and/or imaging characteristics
**# '''<span style="color:#ff0000">If ALL criteria are met (3):</span>'''
**## '''<span style="color:#ff0000">High tumor complexity and PN would be challenging even in experienced hands</span>'''
**## '''<span style="color:#ff0000">No pre-existing CKD or proteinuria</span>'''
**## '''<span style="color:#ff0000">Normal contralateral kidney and new baseline eGFR will likely be > 45 mL/min/1.73m2 even if RN is performed</span>'''
**## '''If ALL are not met, PN should be considered''' unless there are overriding concerns about the safety or oncologic efficacy of PN.
* '''<span style="color:#ff0000">Approach</span>'''
** Can be done via open/laparoscopic/robotic approach
** See Open Kidney Surgery Chapter Notes
* '''2017 AUA Localized RCC Guideline:''' If final pathology shows locally advanced features, adjuvant therapy or clinical trials should be considered


=== Partial vs. radical nephrectomy ===
==== <span style="color:#ff0000">Indications</span> ====
* '''<span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/28479239/ 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer]:</span>'''
*# '''<span style="color:#ff0000">Consider for solid or Bosniak 3/4 complex cystic renal mass whenever increased oncologic potential is suggested</span>''' by tumor size, biopsy, and/or imaging characteristics
*## '''<span style="color:#ff0000">In this setting, RN is preferred If ALL criteria are met (3):</span>'''
*###'''<span style="color:#ff0000">High tumor complexity and PN would be challenging even in experienced hands</span>'''
*###'''<span style="color:#ff0000">No pre-existing CKD or proteinuria</span>'''
*### '''<span style="color:#ff0000">Normal contralateral kidney and new baseline eGFR will likely be > 45 mL/min/1.73m2 even if RN is performed</span>'''
*##*'''<span style="color:#ff0000">If ALL are not met, PN should be considered</span>''' unless there are overriding concerns about the safety or oncologic efficacy of PN.
 
==== Approach ====
* Can be done via open/laparoscopic/robotic approach
*A minimally invasive approach should be considered when it would not compromise oncologic, functional, and perioperative outcomes.
* See [[Open Kidney Surgery|Open Kidney Surgery Chapter Notes]]
 
==== Lymphadenectomy ====
 
* '''Main landing zones for RCC:'''
** '''Right side: interaortocaval'''
** '''Left side: para-aortic'''
*** '''The left kidney drains to the interaortocaval nodes only in advanced disease'''
 
===== Indications =====
*<span style="color:#ff00ff">'''EORTC 30881'''</span>
** '''Objective: evaluate oncologic benefit of lymphadenectomy in cN0 disease'''
** '''Population: 772 patients undergoing radical nephrectomy for cT1-3, N0 suspected RCC'''
** '''Randomized to nephrectomy +/- LND'''
** '''Results:'''
*** Only 4% of patients in the RN plus LND cohort had pN+ disease
****20% of patients with palpable nodes in RN plus LND group were N+ on final pathology; for patients without palpable nodes, 1% was pN+
***'''No difference in overall survival, progression-free survival, or time to progression of disease'''
*** While this is the only randomized trial to address this issue, concerns about EORTC 30881 include the relatively low risk of the patients randomized (≈70% of patients either T1 or T2) and many would be candidates for partial nephrectomy today.
** [https://pubmed.ncbi.nlm.nih.gov/18848382/ Blom JH, van Poppel H, Maréchal JM, et al. Radical nephrectomy with and without lymph-node dissection: final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881. Eur Urol 2009;55:28–34.]
* '''No randomized trials assessing the effect of lymphadenectomy for patients with cN+ disease.'''
** However, a subset of patients with regional lymph node metastases will be cured, or experience prolonged survival following surgery
*2018 systematic review and meta-analysis
**No benefit to LND for in either M0 or M1 RCC
**Suggested that high-risk M0 patient groups warrant further study, as a subset of patients with isolated nodal metastases experience long‐term survival after surgical resection.
** [https://pubmed.ncbi.nlm.nih.gov/29319926/ Bhindi, B, et al. "The role of lymph node dissection in the management of renal cell carcinoma: a systematic review and meta‐analysis." BJU international 121.5 (2018): 684-698.]
*'''Reasons for''' '''limited benefit of routine lymphadenectomy''' (3):
*# RCC metastasizes through the bloodstream independent of the lymphatic system in many patients
*# Lymphatic drainage of the kidney is highly variable.
*## Even an extensive retroperitoneal dissection may not remove all possible sites of metastasis.
*# Low overall incidence of lymph node disease (5%)
 
====== AUA ======
 
* '''2021 AUA'''
** '''cN+: recommended''' for clinically positive nodes (imaging or palpable surgical exploration), primarily for staging and prognostic purposes.
** '''cN0: does not routinely need to be performed''' for localized kidney cancer with clinically negative nodes
 
====== CUA ======
*'''2014 CUA'''
** '''cN0: not routinely recommended'''
**'''cN1M0 disease'''
** '''Lymphadenectomy may be performed for diagnostic purposes in patients with cN1M1 disease'''
 
====== Other sources (8): ======
#'''Enlarged lymph nodes on imaging (cN+)'''
#'''Cytoreductive surgery for metastatic disease'''
#'''Tumor size > 10 cm'''
#'''Nuclear grade 3 or 4'''
#'''Sarcomatoid component'''
#'''Tumor necrosis on imaging'''
#'''Extrarenal tumor extension'''
#'''Tumor thrombus'''
#'''Direct tumoral invasion of adjacent organs'''
* '''Regional lymphadenectomy should be considered in those patients who may have a reasonable chance of benefiting from the added surgery'''.
** Bulky lymphadenopathy carries a poor prognosis similar to metastatic disease, although surgical resection should be considered if feasible and if appropriate, given careful assessment of disease burden and patient age/comorbidities.
 
==== Adrenalectomy ====
 
* '''The ipsilateral adrenal gland should be preserved at the time of the nephrectomy provided it appears normal on imaging and there is no sign of direct tumour invasion'''
** Traditionally, radical nephrectomy included the ipsilateral adrenal gland and complete regional lymphadenectomy from the crus of the diaphragm to the aortic bifurcation, as described by Robson and colleagues in 1969 for management of renal malignancy.
** '''Overall incidence of adrenal metastasis is <5% and removal of the adrenal gland, when not involved by tumor, has not been shown to improve survival of patients with renal cancer.'''
** CT has 99.4% specificity and 99.4% negative predictive value for detecting adrenal involvement
 
===== Indications =====
 
====== AUA ======
* '''2021 AUA (2):'''
** '''Absolute (1):'''
**# '''If preoperative imaging or intraoperative inspection suggests metastasis or adrenal enlargement'''
**#* One exception is when patient has a well-characterized adenoma, which may not mandate surgical excision
** '''Relative (1):'''
**# '''Locally advanced features are identified preoperatively or during exploration and the gland is in close proximity to the tumour'''
**#* Adrenal may be spared in this setting if the contralateral adrenal gland is absent and the ipsilateral gland demonstrates normal morphology and no malignant involvement.
 
====== Other sources (7): ======
# Advanced stage (cT3-4)
# Large upper pole tumors (>7cm) when the surgical plane between the kidney and adrenal gland may be compromised
# Extrarenal tumor extension
# Large tumor size (>10 cm)
# Diffuse involvement by tumor
# Tumor thrombus
# Lymphadenopathy and regional metastasis
=== Partial vs. Radical Nephrectomy ===


* Studies show that CKD increases risk of cardiovascular events and death
* Studies show that CKD increases risk of cardiovascular events and death
Line 274: Line 412:
*** '''In the subgroup analysis of patients with RCC histology, association for OS was extinguished'''
*** '''In the subgroup analysis of patients with RCC histology, association for OS was extinguished'''
** Trial criticisms: premature study closure, trial designed as non-inferiority design but OS significance is based on superiority, patient comorbidity imbalances, cross-over, low statistical power, variable surgical technique and parenchymal sparing
** Trial criticisms: premature study closure, trial designed as non-inferiority design but OS significance is based on superiority, patient comorbidity imbalances, cross-over, low statistical power, variable surgical technique and parenchymal sparing
**[https://pubmed.ncbi.nlm.nih.gov/21186077/ Van Poppel, Hendrik, et al. "A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma." ''European urology'' 59.4 (2011): 543-552.]
* Further studies have suggested that there may be a difference between CKD resulting from medical (CKD-M) and surgical (CKD-S) causes.
* Further studies have suggested that there may be a difference between CKD resulting from medical (CKD-M) and surgical (CKD-S) causes.
** Patients with CKD caused by hypertension or diabetes will continue to suffer from these comorbidities, and will likely experience progressive decline in renal function, eventually affecting survival.
** Patients with CKD caused by hypertension or diabetes will continue to suffer from these comorbidities, and will likely experience progressive decline in renal function, eventually affecting survival.
Line 359: Line 498:
|-
|-
|'''<span style="color:#ff0000">II</span>'''  
|'''<span style="color:#ff0000">II</span>'''  
|'''<span style="color:#ff0000">Below hepatic veins</span>'''
|'''<span style="color:#ff0000">Subhepatic (below hepatic veins)</span>'''
|3%
|3%
|15%
|15%
|-
|-
|'''<span style="color:#ff0000">III</span>'''
|'''<span style="color:#ff0000">III</span>'''
|'''<span style="color:#ff0000">Between hepatic veins and diaphragm</span>'''
|'''<span style="color:#ff0000">Intrahepatic (between hepatic veins and diaphragm)</span>'''
|1%  
|1%  
|5%
|5%
|-
|-
| '''<span style="color:#ff0000">IV</span>'''
| '''<span style="color:#ff0000">IV</span>'''
|'''<span style="color:#ff0000">Above diaphragm</span>'''
|'''<span style="color:#ff0000">Suprahepatic (above diaphragm)</span>'''
|1%  
|1%  
|5%
|5%
Line 413: Line 552:
* After initial management, patients with VHL disease are at much higher risk for local recurrence than patients with sporadic RCC and must be observed closely.
* After initial management, patients with VHL disease are at much higher risk for local recurrence than patients with sporadic RCC and must be observed closely.
* If needing another intervention for recurrence, repeat PN can be challenging because of postoperative fibrosis, and TA may be preferred for local control
* If needing another intervention for recurrence, repeat PN can be challenging because of postoperative fibrosis, and TA may be preferred for local control
=== Lymphadenectomy ===
* '''Main landing zones for RCC:'''
** '''Right side: interaortocaval'''
** '''Left side: para-aortic'''
*** '''The left kidney drains to the interaortocaval nodes only in advanced disease'''
* '''Indications'''
** No randomized trials assessing the effect of lymphadenectomy for patients with cN+ disease.
*** However, a subset of patients with regional lymph node metastases will be cured, or experience prolonged survival following surgery
** '''2014 CUA'''
*** '''cN1M0 disease'''
*** '''Lymphadenectomy may be performed for diagnostic purposes in patients with cN1M1 disease'''
** '''2021 AUA'''
*** '''Clinically concerning regional lymphadenopathy (for staging purposes)'''
** '''Other sources (8):'''
*# '''Enlarged lymph nodes on imaging (cN+)'''
*# '''Cytoreductive surgery for metastatic disease'''
*# '''Tumor size > 10 cm'''
*# '''Nuclear grade 3 or 4'''
*# '''Sarcomatoid component'''
*# '''Tumor necrosis on imaging'''
*# '''Extrarenal tumor extension'''
*# '''Tumor thrombus'''
*# '''Direct tumoral invasion of adjacent organs'''
** '''Regional lymphadenectomy should be considered in those patients who may have a reasonable chance of benefiting from the added surgery'''.
*** Bulky lymphadenopathy carries a poor prognosis similar to metastatic disease, although surgical resection should be considered if feasible and if appropriate, given careful assessment of disease burden and patient age/comorbidities.
** '''CUA/AUA: Routine lymphadenectomy at the time of RN or PN is not routinely recommended in patients with clinical N0 disease.'''
*** Reasons for '''limited benefit of routine lymphadenectomy''' (3):
***# RCC metastasizes through the bloodstream independent of the lymphatic system in many patients
***# Lymphatic drainage of the kidney is highly variable.
***## Even an extensive retroperitoneal dissection may not remove all possible sites of metastasis.
***# Low overall incidence of lymph node disease (5%)
** '''EORTC 30881'''
*** Objective: evaluate oncologic benefit of lymphadenectomy in cN0 disease
*** Population: 772 patients undergoing radical nephrectomy for cT1-3, N0 suspected RCC
*** Randomized to nephrectomy +/- LND
*** Results:
**** No difference in overall survival, progression-free survival, or time to progression of disease
**** While this is the only randomized trial to address this issue, concerns about EORTC 30881 include the relatively low risk of the patients randomized (≈70% of patients either T1 or T2) and many would be candidates for partial nephrectomy today. Only 4% of patients undergoing LND were found to have positive nodes again indicating a low-risk cohort.
*** Blom JH, van Poppel H, Maréchal JM, et al. Radical nephrectomy with and without lymph-node dissection: final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881. Eur Urol 2009;55:28–34.
** A more recent systematic review and meta-analysis found no benefit to LND for in either M0 or M1 RCC, but suggested that high-risk M0 patient groups warrant further study, as a subset of patients with isolated nodal metastases experience long‐term survival after surgical resection.
*** Bhindi, B, et al. "The role of lymph node dissection in the management of renal cell carcinoma: a systematic review and meta‐analysis." BJU international 121.5 (2018): 684-698.
* '''If lymph node involvement is confirmed on pathology, consider referral to medical oncology'''
=== Adrenalectomy ===
* '''The ipsilateral adrenal gland should be preserved at the time of the nephrectomy provided it appears normal on imaging and there is no sign of direct tumour invasion'''
** Traditionally, radical nephrectomy included the ipsilateral adrenal gland and complete regional lymphadenectomy from the crus of the diaphragm to the aortic bifurcation, as described by Robson and colleagues in 1969 for management of renal malignancy.
** '''Overall incidence of adrenal metastasis is <5% and removal of the adrenal gland, when not involved by tumor, has not been shown to improve survival of patients with renal cancer.'''
** CT has 99.4% specificity and 99.4% negative predictive value for detecting adrenal involvement
* '''Indications'''
** '''2021 AUA (2):'''
*** '''Absolute (1):'''
***# '''If preoperative imaging or intraoperative inspection suggests metastasis or adrenal enlargement'''
***#* One exception is when patient has a well-characterized adenoma, which may not mandate surgical excision
*** '''Relative (1):'''
***# '''Locally advanced features are identified preoperatively or during exploration and the gland is in close proximity to the tumour'''
***#* Adrenal may be spared in this setting if the contralateral adrenal gland is absent and the ipsilateral gland demonstrates normal morphology and no malignant involvement.
** Other sources (7):
**# Advanced stage (cT3-4)
**# Large upper pole tumors (>7cm) when the surgical plane between the kidney and adrenal gland may be compromised
**# Extrarenal tumor extension
**# Large tumor size (>10 cm)
**# Diffuse involvement by tumor
**# Tumor thrombus
**# Lymphadenopathy and regional metastasis
* '''If adrenal involvement is confirmed on final pathology, consider referral to medical oncology'''
=== Minimally invasive approach ===
* Should be considered when it would not compromise oncologic, functional and perioperative outcomes


=== Pathologic evaluation of the adjacent renal parenchyma ===
=== Pathologic evaluation of the adjacent renal parenchyma ===
Line 494: Line 560:
* College of American Pathologists established a requirement that pathologic evaluation of the renal parenchyma for possible nephrologic disease should be included in all synoptic reports for kidney cancer.
* College of American Pathologists established a requirement that pathologic evaluation of the renal parenchyma for possible nephrologic disease should be included in all synoptic reports for kidney cancer.


=== Referral to Medical Oncology ===
*'''Indications (2):'''
*#'''Concern for potential clinical metastasis'''
*#'''Lymph node involvement is confirmed on pathology'''
*#'''Adrenal involvement is confirmed on final pathology'''
*#'''Incompletely resected disease (macroscopic positive margin or gross residual disease)'''
== Management summary (as per 2014 CUA Surgical Management of RCC Consensus Statement) ==
== Management summary (as per 2014 CUA Surgical Management of RCC Consensus Statement) ==


Line 581: Line 653:


* '''Neoadjuvant therapy is defined as pre-operative medical treatment for patients undergoing definitive surgical resection of their kidney cancer with curative intent (i.e., non-metastatic disease).'''
* '''Neoadjuvant therapy is defined as pre-operative medical treatment for patients undergoing definitive surgical resection of their kidney cancer with curative intent (i.e., non-metastatic disease).'''
** Aims of neoadjuvant therapy for locally advanced disease (5):
* Aims of neoadjuvant therapy for locally advanced disease (5):
**# Reduce the risk of recurrence
*# Reduce the risk of recurrence
**# Reduce the size of tumours to make unresectable tumours resectable
*# Reduce the size of tumours to make unresectable tumours resectable
**# Make PN more feasible
*# Make PN more feasible
**# Reduce the rate of positive surgical margins
*# Reduce the rate of positive surgical margins
**# Simplify the resection of venous thrombus
*# Simplify the resection of venous thrombus
* '''Indications'''
 
** '''2019 CUA Management of Advanced Kidney Cancer Consensus Statement: currently there is no role for neoadjuvant therapy or pre-surgical therapy outside of a clinical trial'''
=== Indications ===
 
==== CUA ====
*'''2019 CUA Management of Advanced Kidney Cancer Consensus Statement: currently there is no role for neoadjuvant therapy or pre-surgical therapy outside of a clinical trial'''


== Adjuvant therapy for RCC ==
== Adjuvant Therapy for RCC ==


* '''Adjuvant therapy is defined as post-operative medical therapy after surgical resection with definitive curative intent.'''
* '''Adjuvant therapy is defined as post-operative medical therapy after surgical resection with definitive curative intent.'''
Line 599: Line 674:
**# Unfavourable histology
**# Unfavourable histology
**# Nodal involvement
**# Nodal involvement
* '''Indications'''
** '''2019 CUA: adjuvant therapy is not currently recommended outside of a clinical trial'''
** '''2021 AUA: standard of care for patients with fully resected renal cancers remains close clinical and radiographic observation.''' Patients with a high risk of recurrence should be counseled regarding systemic adjuvant options and/or considered for enrollment into adjuvant clinical trials
* '''Treatments'''
** Despite demonstrable anti-tumor effects in patients with metastatic disease, one RCT with IL-2 and 3 RCTs with interferon alfa did not prove to be beneficial in the adjuvant setting.
** A variety of autologous tumor vaccine–based approaches have been used in the postoperative setting with negative results
** '''S-TRAC'''
*** '''Population: 615 nephrectomy patients with either ccRCC and non-ccRCC, high-risk according to modified UISS (≥T3, regional lymph-node metastasis, or both)'''
**** '''Higher risk than ASSURE'''
*** '''Randomized to sunitnib vs. placebo.'''
**** Sunitnib started within 3 months of nephrectomy
*** '''Results:'''
**** '''Adjuvant sunitnib significantly improved DFS (improvement comparable to time on therapy) but not OS'''
**** '''Adjuvant sunitnib FDA approved in 2017, not approved in Canada'''
*** Ravaud, Alain, et al."Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy." ''New england journal of medicine'' 375.23 (2016): 2246-2254. '''ASSURE'''
*** '''Population: 1934 nephrectomy patients with ccRCC, pT1b G3−4 N0 (or pNX where clinically N0) M0 to T (any) G (any) N + (fully resected)'''
*** '''Randomized to sunitinib vs. sorafenib vs. placebo'''
*** '''Results:'''
**** '''No significant difference in DFS or OS between the 3 treatment arms'''
**** '''Dose reductions were necessary during study due to a high attrition rate from treatment intolerability'''
*** Haas, Naomi B., et al."Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial." ''The Lancet'' 387.10032 (2016): 2008-2016.
** '''PROTECT'''
*** Population: 1500 nephrectomy patients with intermediate and high-risk disease
*** Randomized to pazopanib vs. placebo
*** Results:
**** No significant difference in DFS or OS
**** Many required dose reduction due to high attrition rates
*** Motzer, Robert J., et al."Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma." ''Journal of Clinical Oncology'' 35.35 (2017): 3916.
** '''SORCE'''
*** A phase III randomized double-blind study comparing sorafenib to placebo in patients with resected intermediate- to high-risk RCC
** '''EVEREST'''
*** Randomizing nephrectomy patients to everolimus vs. placebo
** '''ATLAS'''
*** Population: 724 nephrectomy patients with ≥pT2 and/or N+, any Fuhrman grade RCC
*** Randomized to adjuvant to axitnib vs. placebo
*** Results:
**** Trial was stopped due to futility at the prespecified interim analysis, with no significant difference in DFS observed at that time
** '''ARIZER'''
*** Population: 864 nephrectomy patients with ccRCC, pT3/pT4Nx/N0M0 or pTanyN+M0 or pT1b/pT2Nx/N0M0 with nuclear grade 3 or greater
*** Randomized to girentuximab vs. placebo
** '''PROSPER'''
*** Randomizing nephrectomy patients to nivolumab vs. placebo
** '''IMotion'''
*** Randomizing nephrectomy patients to atezolizumab vs. placebo
***


== Follow-up After Treatment of Non-metastatic RCC ==
=== Indications ===
 
==== AUA ====
 
* '''<span style="color:#ff0000">2021 AUA</span>'''
** '''<span style="color:#ff0000">Standard of care for patients with fully resected renal cancers remains close clinical and radiographic observation.</span>''' Patients with a high risk of recurrence should be counseled regarding systemic adjuvant options and/or considered for enrollment into adjuvant clinical trials
 
==== CUA ====
*'''2019 CUA'''
**'''Adjuvant therapy is not currently recommended outside of a clinical trial'''
 
=== Treatments ===
* Despite demonstrable anti-tumor effects in patients with metastatic disease, one RCT with IL-2 and 3 RCTs with interferon alfa did not prove to be beneficial in the adjuvant setting.
* A variety of autologous tumor vaccine–based approaches have been used in the postoperative setting with negative results
*'''<span style="color:#ff00ff">KEYNOTE-564 (NEJM 2021)</span>'''
** '''Population: 496 patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy'''
***'''High-risk for recurrence defined by (4)'''
***#'''Tumor stage 2 with nuclear grade 4 or sarcomatoid differentiation'''
***#'''Tumor stage 3 or higher'''
***#'''Regional lymph-node metastasis'''
***#'''Stage M1 with NED'''
** '''Randomized to pembrolizumab vs. placebo'''
** '''Primary outcome: disease-free survival'''
** '''Results:'''
*** '''Disease-free survival significantly improved with pembrolizumab'''
*** Absolute survival benefit at 24 months: 3.1% (96.6% pembrolizumab vs. 93.5% placebo)
** [https://pubmed.ncbi.nlm.nih.gov/34407342/ Choueiri, Toni K., et al."Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma." ''The New England Journal of Medicine'' 385.8 (2021): 683-694.]
*'''S-TRAC'''
** '''Population: 615 nephrectomy patients with either ccRCC and non-ccRCC, high-risk according to modified UISS (≥T3, regional lymph-node metastasis, or both)'''
*** '''Higher risk than ASSURE'''
** '''Randomized to sunitnib vs. placebo.'''
*** Sunitnib started within 3 months of nephrectomy
** '''Results:'''
*** '''Adjuvant sunitnib significantly improved DFS (improvement comparable to time on therapy) but not OS'''
*** '''Adjuvant sunitnib FDA approved in 2017, not approved in Canada'''
** Ravaud, Alain, et al."Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy." ''New england journal of medicine'' 375.23 (2016): 2246-2254. '''ASSURE'''
** '''Population: 1934 nephrectomy patients with ccRCC, pT1b G3−4 N0 (or pNX where clinically N0) M0 to T (any) G (any) N + (fully resected)'''
** '''Randomized to sunitinib vs. sorafenib vs. placebo'''
** '''Results:'''
*** '''No significant difference in DFS or OS between the 3 treatment arms'''
*** '''Dose reductions were necessary during study due to a high attrition rate from treatment intolerability'''
** Haas, Naomi B., et al."Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial." ''The Lancet'' 387.10032 (2016): 2008-2016.
* '''PROTECT'''
** Population: 1500 nephrectomy patients with intermediate and high-risk disease
** Randomized to pazopanib vs. placebo
** Results:
*** No significant difference in DFS or OS
*** Many required dose reduction due to high attrition rates
** Motzer, Robert J., et al."Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma." ''Journal of Clinical Oncology'' 35.35 (2017): 3916.
* '''SORCE'''
** A phase III randomized double-blind study comparing sorafenib to placebo in patients with resected intermediate- to high-risk RCC
* '''EVEREST'''
** Randomizing nephrectomy patients to everolimus vs. placebo
* '''ATLAS'''
** Population: 724 nephrectomy patients with ≥pT2 and/or N+, any Fuhrman grade RCC
** Randomized to adjuvant to axitnib vs. placebo
** Results:
*** Trial was stopped due to futility at the prespecified interim analysis, with no significant difference in DFS observed at that time
* '''ARIZER'''
** Population: 864 nephrectomy patients with ccRCC, pT3/pT4Nx/N0M0 or pTanyN+M0 or pT1b/pT2Nx/N0M0 with nuclear grade 3 or greater
** Randomized to girentuximab vs. placebo
* '''PROSPER'''
** Randomizing nephrectomy patients to nivolumab vs. placebo
* '''IMotion'''
** Randomizing nephrectomy patients to atezolizumab vs. placebo
**
 
== Follow-up after Treatment ==
 
=== Follow-up after Surgery for Malignant Mass ===


* Discuss patient's risk of recurrence based on tumour histology, stage, grade, and surgical margin status
* Discuss patient's risk of recurrence based on tumour histology, stage, grade, and surgical margin status
* '''Rationale for surveillance'''
 
** '''Monitor for (3):'''
==== Rationale for surveillance ====
**# '''Post-operative complications'''
* '''Monitor for (3):'''
**# '''Renal function'''
*# '''Post-operative complications'''
**# '''Recurrence'''
*# '''Renal function'''
**## '''Local'''
*# '''Recurrence'''
**## '''Contralateral kidney'''
*## '''Local'''
**## '''Distant'''
*## '''Contralateral kidney'''
** '''Renal function'''
*## '''Distant'''
*** '''Decreases postoperatively and usually improves over time until a new baseline is achieved in ≈3–6 months.'''
* '''Renal function'''
*** '''Long-term monitoring of serum creatinine, eGFR, and proteinuria is recommended.'''
** '''Decreases postoperatively and usually improves over time until a new baseline is achieved in ≈3–6 months.'''
**** The aim of renal function surveillance is to prevent or delay CKD and avoid dialysis.
** '''Long-term monitoring of serum creatinine, eGFR, and proteinuria is recommended.'''
*** '''Consider nephrology referral if eGFR <45 ml/min/1.73m2 or progressive CKD develops after surgery, especially if associated with proteinuria'''
*** The aim of renal function surveillance is to prevent or delay CKD and avoid dialysis.
** '''Recurrence'''
** '''Consider nephrology referral if eGFR <45 ml/min/1.73m2 or progressive CKD develops after surgery, especially if associated with proteinuria'''
*** '''Most common locations of the first recurrence (4):'''
* '''Recurrence'''
**** '''Most common: Lung''' (54%)
** '''Most common locations of the first recurrence (4):'''
**** '''Lymph nodes''' (22%)
*** '''Most common: Lung''' (54%)
**** '''Bone''' (20%)
*** '''Lymph nodes''' (22%)
**** '''Liver''' (15%)
*** '''Bone''' (20%)
*** '''Metastases to the'''
*** '''Liver''' (15%)
**** '''Abdomen and thorax are usually asymptomatic'''
** '''Metastases to the'''
**** '''Brain and bone are symptomatic in most cases''' (98% and 90%, respectively). These lesions become symptomatic quickly.
*** '''Abdomen and thorax are usually asymptomatic'''
** '''Early diagnosis of local and contralateral kidney recurrence (incidence <2%) is useful, since the majority can be cured with treatment'''
*** '''Brain and bone are symptomatic in most cases''' (98% and 90%, respectively). These lesions become symptomatic quickly.
* '''Surveillance'''
* '''Early diagnosis of local and contralateral kidney recurrence (incidence <2%) is useful, since the majority can be cured with treatment'''
** '''Risk-stratified'''
 
*** '''2021 AUA Guidelines (4):'''
==== Investigations ====
***# '''Low-risk: pT1 and Grade 1/2'''
* '''History and Physical Exam'''
***# '''Intermediate-risk: pT1 and Grade 3/4, or pT2 any Grade'''
** History
***# '''High-risk: pT3 any Grade'''
***Signs and Symptoms
***# '''Very high-risk: pT4 or pN1, or sarcomatoid/rhabdoid dedifferentiation, or macroscopic positive margin'''
****Associated with disease recurrence/progression: weight loss, night sweats, shortness of breath, pleuritic chest pain, hemoptysis, epistaxis, dermatologic involvement, musculoskeletal pain, weakness, or focal neurological deficits
**** '''If final microscopic surgical margins are positive for cancer, the risk category should be considered at least one level higher''', and increased clinical vigilance should be exercised.
** Physical exam
*** '''2018 CUA Guidelines (4):'''
*** Abdomen/abdominal wall
***# '''Low-risk: pT1'''
****Masses
***# '''Intermediate-risk: pT2'''
*** Lymphadenopathy
***# '''High-risk: pT3-4'''
****Supraclavicular
***# '''Very high-risk: N+'''
****Axillary
** '''Investigations'''
****Groin
*** '''History and physical exam'''
*** Lower extremity edema
**** Signs and symptoms of disease recurrence/progression: weight loss, night sweats, shortness of breath, pleuritic chest pain, hemoptysis, epistaxis, dermatologic involvement, musculoskeletal pain, weakness, or focal neurological deficits
****Might suggest recurrence with IVC involvement
**** Physical exam should assess for
* '''Laboratory'''
***** Masses in the abdomen/abdominal wall
** '''2021 AUA (2):'''
***** Lymphadenopathy (supraclavicular, axiallary, groin)
**# '''<span style="color:#ff0000">Serum creatinine, eGFR'''
***** Lower extremity edema that might suggest recurrence with IVC involvement
**# '''<span style="color:#ff0000">Urinalysis'''
*** '''Laboratory'''
*** '''Other laboratory evaluations (e.g., complete blood count, lactate dehydrogenase, liver function tests, alkaline phosphatase and calcium level) may be obtained at the discretion of the clinician or if advanced disease is suspected.'''
**** '''2018 CUA (4):'''
*** With significant nephron mass loss, hyperfiltration can occur resulting in glomerular damage, exacerbation of proteinuria and progressive sclerosis with further decline in GFR., Therefore, 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
****# '''Serum creatinine, eGFR'''
*** Patients found to have progressive renal insufficiency or proteinuria should be referred to nephrology
****# '''Serum chemistries'''
**'''2018 CUA (4):'''
****# '''CBC'''
**# '''Serum creatinine, eGFR'''
****# '''LFTs'''
**# '''Serum chemistries'''
**** '''2021 AUA (2):'''
**# '''CBC'''
****# '''Serum creatinine, eGFR'''
**# '''LFTs'''
****# '''Urinalysis'''
* '''Imaging'''
***** Other laboratory evaluations (e.g., complete blood count, lactate dehydrogenase, liver function tests, alkaline phosphatase and calcium level) may be obtained at the discretion of the clinician or if advanced disease is suspected.
** '''Regional'''
***** With significant nephron mass loss, hyperfiltration can occur resulting in glomerular damage, exacerbation of proteinuria and progressive sclerosis with further decline in GFR., Therefore, 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
*** '''Abdominal imaging'''
***** Patients found to have progressive renal insufficiency or proteinuria should be referred to nephrology
**** '''CT or MRI pre- and post-intravenous contrast preferred'''
*** '''Imaging'''
***** '''MRI''' has acceptable accuracy to detect musculoskeletal and lymph node metastases, but '''lower sensitivity to detect pulmonary metastases when compared to CT'''
**** '''Regional'''
** '''Distant'''
***** '''Abdominal imaging'''
*** '''Chest'''
****** '''CT or MRI pre- and post-intravenous contrast preferred'''
*** Bone scan
******* '''MRI''' has acceptable accuracy to detect musculoskeletal and lymph node metastases, but '''lower sensitivity to detect pulmonary metastases when compared to CT'''
**** Not indicated in routine follow-up of treated malignant renal mass
****** See schedule below
***** These metastases are usually symptomatic
**** '''Distant'''
**** Indications
***** '''Chest'''
***** 2021 AUA (3):
****** See schedule below
*****# Bone pain
***** Bone scan
*****# Elevated alkaline phosphatase
****** Not indicated in routine follow-up of treated malignant renal mass
*****# Radiographic findings suggestive of a bony neoplasm
******* These metastases are usually symptomatic
*** CT/MRI brain and/or spine
****** Indications
**** Not indicated in routine follow-up of treated malignant renal mass
******* 2021 AUA (3):
***** These metastases are usually symptomatic
*******# Bone pain
**** Indication (1):
*******# Elevated alkaline phosphatase
****# Acute neurological signs or symptoms
*******# Radiographic findings suggestive of a bony neoplasm
**** Modality
***** CT/MRI brain and/or spine
***** MRI is the most sensitive and specific imaging test for detection of metastatic neoplasms to the brain
****** Not indicated in routine follow-up of treated malignant renal mass
** Other
******* These metastases are usually symptomatic
*** Additional site-specific imaging can be ordered as warranted by clinical symptoms suggestive of recurrence or metastatic spread
****** Indication (1):
*** Positron emission tomography (PET) scan should not be obtained routinely but may be considered selectively.
******# Acute neurological signs or symptoms
**** '''Fluoride PET-CT is more sensitive at detecting RCC skeletal metastases than bone scintigraphy or CT'''.
****** Modality
**** Currently, PET-CT is not a standard exam for diagnosis, staging, or surveillance in RCC.
******* MRI is the most sensitive and specific imaging test for detection of metastatic neoplasms to the brain
 
**** Other
==== Risk Stratification ====
***** Additional site-specific imaging can be ordered as warranted by clinical symptoms suggestive of recurrence or metastatic spread
 
***** Positron emission tomography (PET) scan should not be obtained routinely but may be considered selectively.
===== AUA =====
****** '''Fluoride PET-CT is more sensitive at detecting RCC skeletal metastases than bone scintigraphy or CT'''.
* '''<span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/28479239/ 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer (4):]</span>'''
****** Currently, PET-CT is not a standard exam for diagnosis, staging, or surveillance in RCC.
*# '''<span style="color:#ff0000">Low-risk: pT1 and Grade 1/2'''
** '''Schedule'''
*# '''<span style="color:#ff0000">Intermediate-risk: pT1 and Grade 3/4, or pT2 any Grade'''
*** '''2021 AUA'''
*# '''<span style="color:#ff0000">High-risk: pT3 any Grade'''
**** '''See Table 1 from original 2021 AUA Guidelines'''
*# '''<span style="color:#ff0000">Very high-risk: pT4 or pN1, or sarcomatoid/rhabdoid dedifferentiation, or macroscopic positive margin'''
**** '''Imaging for at least 5 years:'''
** '''If final microscopic surgical margins are positive for cancer, the risk category should be considered at least one level higher''', and increased clinical vigilance should be exercised.
***** '''Abdominal'''
 
****** '''After 2 years, abdominal ultrasound (US) alternating with cross-sectional imaging may be considered in the low- and intermediate-risk groups at physician discretion.'''
===== CUA =====
****** '''After 5 years, informed/shared decision-making should dictate further abdominal imaging.'''
*'''2018 CUA Guidelines (4):'''
******* The option to use abdominal US instead of CT or MRI s intended to allow continuous monitoring after 5 years, while minimizing radiation exposure/cost in the LR and IR groups.
*# '''Low-risk: pT1'''
***** '''Chest'''
*# '''Intermediate-risk: pT2'''
****** '''Modality'''
*# '''High-risk: pT3-4'''
******* '''Chest x-ray low- and intermediate-risk groups'''
*# '''Very high-risk: N+'''
******* '''CT chest for high and very high-risk groups.'''
 
****** After 5 years, informed/shared decision-making discussion should dictate further chest imaging and chest x-ray may be utilized instead of chest CT for high and very high-risk groups.
==== Schedule ====
*** '''2018 CUA'''
 
**** '''See Table 1 from Original Guideline for Surveillance Schedule'''
===== AUA =====
**** '''If patient is symptomatic or has an abnormal blood test, earlier radiological investigations may be indicated'''
* <span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/28479239/ '''2021 AUA Guidelines on Renal Mass and Localized Renal Cancer''']</span>
**** '''Low-risk (pT1)'''
** '''<span style="color:#ff0000">See [https://www.auanet.org/documents/Guidelines/PDF/RCC-Follow-Up-Algorithm.pdf Table 1] from Original 2021 AUA Guidelines'''
***** '''Abdominal imaging (CT/MRI/US) is recommended at 24 and 60 months'''
***'''<span style="color:#ff0000">If low-risk, abdominal and chest imaging at 12, 24, 48 and 60 months'''
****** US is less sensitive than CT, however, its use is justifiable and cost-effective in patients with a minimal risk of abdominal recurrence and lower BMI
*** '''<span style="color:#ff0000">If intermediate-risk, abdominal and chest imaging at 6, 12, 24, 36, 48 and 60 months'''
***** '''Follow-up is the same for PN for lesions <4 cm,''' since local recurrence rates in this population are similar to RN
** '''Imaging for at least 5 years'''
****** '''Postoperative CT abdomen at 3–12 months is optional for patients treated with PN to evaluate the residual baseline renal appearance'''
*** '''Abdominal'''
***** '''Routine imaging beyond 5 years is optional and can be risk-adapted'''
**** '''After 2 years, abdominal ultrasound (US) alternating with cross-sectional imaging may be considered in the low- and intermediate-risk groups at physician discretion.'''
**** '''Intermediate-risk (pT2)'''
**** '''After 5 years, informed/shared decision-making should dictate further abdominal imaging.'''
***** '''Abdominal imaging (CT/MRI/US) recommended at 12, 24, 36, and 60 months'''
***** The option to use abdominal US instead of CT or MRI s intended to allow continuous monitoring after 5 years, while minimizing radiation exposure/cost in the LR and IR groups.
***** '''Routine imaging beyond 5 years is at the discretion of the treating physician'''
*** '''Chest'''
**** '''High-risk (pT3-4)'''
**** '''Modality'''
***** '''Abdominal CT or MRI is recommended every 6 months for 2 years, then at 36 and 60 months, then every 2 years'''
***** '''Chest x-ray low- and intermediate-risk groups'''
**** '''Very high-risk (N+)'''
***** '''CT chest for high and very high-risk groups.'''
***** '''Abdominal CT or MRI is recommended at 3 and 6 months, then every 6 months for 3 years, then yearly'''
**** After 5 years, informed/shared decision-making discussion should dictate further chest imaging and chest x-ray may be utilized instead of chest CT for high and very high-risk groups.
**** '''Imaging'''
 
***** '''Abdomen'''
===== CUA =====
****** '''CT abdomen/pelvis recommended,''' particularly in cases of tumour-associated symptoms
*'''2018 CUA'''
******* '''Abdominal US may be performed for lower-risk patients (pT1 and pT2)'''
** '''See Table 1 from Original Guideline for Surveillance Schedule'''
***** '''Chest'''
** '''If patient is symptomatic or has an abnormal blood test, earlier radiological investigations may be indicated'''
****** '''Modality'''
** '''Low-risk (pT1)'''
******* '''CXR recommended'''
*** '''Abdominal imaging (CT/MRI/US) is recommended at 24 and 60 months'''
******* '''CT chest in higher-risk patients''' due to the higher sensitivity of this test compared to CXR
**** US is less sensitive than CT, however, its use is justifiable and cost-effective in patients with a minimal risk of abdominal recurrence and lower BMI
******** Can consider alternating CT chest with CXR
*** '''Follow-up is the same for PN for lesions <4 cm,''' since local recurrence rates in this population are similar to RN
* '''Follow-up after ablation'''
**** '''Postoperative CT abdomen at 3–12 months is optional for patients treated with PN to evaluate the residual baseline renal appearance'''
** '''Patients who have undergone ablation should be followed with contrast-enhanced imaging (MRI or CT)''' to assess for residual enhancing disease and post-procedure complications.
*** '''Routine imaging beyond 5 years is optional and can be risk-adapted'''
*** '''Ultrasound should not be used for post-ablation surveillance'''
** '''Intermediate-risk (pT2)'''
** '''Schedule'''
*** '''Abdominal imaging (CT/MRI/US) recommended at 12, 24, 36, and 60 months'''
*** '''2021 AUA'''
*** '''Routine imaging beyond 5 years is at the discretion of the treating physician'''
**** '''If biopsy confirmed malignancy or was non-diagnostic, pre- and post-contrast cross-sectional abdominal imaging should be done within 6 months after TA.'''
** '''High-risk (pT3-4)'''
**** '''Subsequent follow-up should be according to the intermediate-risk recommendations (see Table 1 from original guidelines)'''
*** '''Abdominal CT or MRI is recommended every 6 months for 2 years, then at 36 and 60 months, then every 2 years'''
*** '''2018 CUA'''
** '''Very high-risk (N+)'''
**** '''Surveillance is similar to low-risk except for abdominal imaging (CT or MRI) at 3, 6, and 12 months, then annually thereafter for up to 5 years.'''
*** '''Abdominal CT or MRI is recommended at 3 and 6 months, then every 6 months for 3 years, then yearly'''
***** '''CXR is recommended annually during follow-up'''
** '''Imaging'''
**** If pre-treatment biopsy demonstrated oncocytoma and imaging post-ablation shows treatment success, routine imaging beyond one year is not recommended
*** '''Abdomen'''
* '''Follow-up after surgical treatment of benign renal mass'''
**** '''CT abdomen/pelvis recommended,''' particularly in cases of tumour-associated symptoms
** 2021 AUA:
***** '''Abdominal US may be performed for lower-risk patients (pT1 and pT2)'''
*** Should undergo at least one postoperative visit to assess patient recovery and laboratory testing to assess renal function.
*** '''Chest'''
*** Further surveillance for adverse sequelae of treatment, such as progressive decline in renal function, may also be required selectively.
**** '''Modality'''
** Patients who have only had a biopsy without definitive management, may carry a small risk of a missed malignancy and should be considered for surveillance.
***** '''CXR recommended'''
***** '''CT chest in higher-risk patients''' due to the higher sensitivity of this test compared to CXR
****** Can consider alternating CT chest with CXR
 
=== Follow-up after ablation ===
* '''Patients who have undergone ablation should be followed with contrast-enhanced imaging (MRI or CT)''' to assess for residual enhancing disease and post-procedure complications.
** '''Ultrasound should not be used for post-ablation surveillance'''
* '''Schedule'''
** '''2021 AUA'''
*** '''If biopsy confirmed malignancy or was non-diagnostic, pre- and post-contrast cross-sectional abdominal imaging should be done within 6 months after TA.'''
*** '''Subsequent follow-up should be according to the intermediate-risk recommendations (see Table 1 from original guidelines)'''
** '''2018 CUA'''
*** '''Surveillance is similar to low-risk except for abdominal imaging (CT or MRI) at 3, 6, and 12 months, then annually thereafter for up to 5 years.'''
**** '''CXR is recommended annually during follow-up'''
*** If pre-treatment biopsy demonstrated oncocytoma and imaging post-ablation shows treatment success, routine imaging beyond one year is not recommended
 
=== Follow-up after Surgery for Benign Mass ===
* 2021 AUA:
** Should undergo at least one postoperative visit to assess patient recovery and laboratory testing to assess renal function.
** Further surveillance for adverse sequelae of treatment, such as progressive decline in renal function, may also be required selectively.
* Patients who have only had a biopsy without definitive management, may carry a small risk of a missed malignancy and should be considered for surveillance.


== Local Recurrence after Radical Nephrectomy or Nephron-Sparing Surgery ==
== Local Recurrence after Radical Nephrectomy or Nephron-Sparing Surgery ==