Editing Management of Localized and Locally Advanced Disease (section)

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

=== Established Treatment Options for Localized Prostate Cancer ===

==== <span style="color:#ff0000">Options (4):</span> ====
# '''<span style="color:#ff0000">Active surveillance (AS)/expectant management</span>'''
# '''<span style="color:#ff0000">Thermal ablation (TA)</span>'''
# '''<span style="color:#ff0000">Partial nephrectomy (PN)</span>'''
# '''<span style="color:#ff0000">Radical nephrectomy (RN)</span>'''

==== Patient counseling ====
* Review the most common and serious urologic and non-urologic morbidities of each treatment pathway.
* 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 at baseline because of the shared risk factors with RCC and CKD, such as hypertension.
** '''Predictive factors for post-operative development of CKD or progression of pre-existing CKD (8):'''
**# '''Older age'''
**# '''Diabetes'''
**# '''Hypertension'''
**# '''Male sex'''
**# '''Obesity'''
**# '''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 ===

==== Advantages/Disadvantages ====
*'''Advantage'''
*# '''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'''
*# '''Patient anxiety'''
*# '''Oncologic risks'''
*## '''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.

==== Indications ====

===== 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">Absolute (1):</span>'''
**# '''<span style="color:#ff0000">Risk of intervention/competing risks of death outweighs the potential benefits of intervention</span>'''
** '''<span style="color:#ff0000">Relative (9):</span>'''
*** '''<span style="color:#ff0000">Tumour factors (2)</span>'''
**# '''<span style="color:#ff0000">Solid renal mass < 2cm</span>'''
**# '''<span style="color:#ff0000">Complex but predominantly cystic renal masses</span>'''
*** '''<span style="color:#ff0000">Patient factors (7)</span>'''
**# '''<span style="color:#ff0000">Elderly</span>'''
**# '''<span style="color:#ff0000">Life expectancy < 5 years</span>'''
**# '''<span style="color:#ff0000">High calculated comorbidities</span>'''
**# '''<span style="color:#ff0000">Excessive perioperative risk</span>'''
**# '''<span style="color:#ff0000">Poor functional status</span>'''
**# '''<span style="color:#ff0000">Marginal renal function (≥CKD3b)</span>'''
**# '''<span style="color:#ff0000">Patient preference</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.
**#* 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.
**#** In this setting, renal mass biopsy (if the mass is predominantly solid) is encouraged for additional risk stratification.
**#** If the patient continues to prefer AS, close clinical and cross-sectional imaging surveillance with periodic reassessment and counseling should be recommended.

===== NCCN =====
*'''<span style="color:#ff0000">2024 NCCN</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">In select patients with clinical stage T1b tumors (partial nephrectomy or radical nephrectomy are primary treatment options while active surveillance and ablative techniques are for select patients)</span>'''

===== CUA =====

* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932428/ '''2022 CUA Guidelines on Management of Small Renal Masses''']
** '''<span style="color:#ff0000">Preferred strategy for patients with a suspected renal malignancy measuring <2 cm in diameter'''
** '''<span style="color:#ff0000">Suggested as management option for patients with a suspected renal malignancy measuring 2–4 cm in diameter'''
*** '''Definitive treatment (partial nephrectomy or percutaneous thermal ablation) are also management options for patients with a suspected renal malignancy measuring 2–4 cm in diameter'''
**For patients with a SRM suspicious for renal malignancy AND significant comorbidities and/or limited life expectancy, observation (or watchful waiting) is recommended as the preferred strategy for patients 

===== EAU =====

* [https://uroweb.org/guidelines/renal-cell-carcinoma/chapter/disease-management 2024 EAU Guidelines on Renal Cell Carcinoma]
** Offer active surveillance (AS) or tumour ablation (TA) to frail and/or comorbid patients with small renal masses.

==== Contraindications ====
* '''In general, AS is not appropriate'''
** '''Larger (>3-4 cm), poorly marginated, or nonhomogeneous solid renal lesions'''
** '''Biopsy indicates a potentially aggressive RCC, except in patients with limited life expectancy'''
* '''AS is also not advisable in younger, otherwise healthy, patients with small, solid tumors that have radiographic characteristics consistent with RCC'''

==== Indications for intervention (treatment or AS intensity) ====

===== AUA =====
* '''<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">Tumour size >3cm</span>'''
*# '''<span style="color:#ff0000">Growth kinetics (>5mm/year)</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>'''
*# '''<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)

===== CUA =====
*'''<span style="color:#ff0000">2022 CUA (4)</span>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932428/]'''
*#'''<span style="color:#ff0000">Growth of tumor to >4 cm'''
*#'''<span style="color:#ff0000">Consecutive growth rate >0.5 cm/year'''
*#'''<span style="color:#ff0000">Progression to metastases'''
*#'''<span style="color:#ff0000">Patient’s choice'''

==== <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) ===

* '''Appropriate in patients in whom treatment poses an unacceptably higher risk than surveillance'''
* Yearly abdominal US including images of the retroperitoneal and intraperitoneal organs can be performed to screen for stage progression which may trigger systemic therapy in the appropriately selected patient

=== Thermal ablation (TA) ===

==== <span style="color:#ff0000">Options (2):</span> ====
# '''<span style="color:#ff0000">Radiofrequency ablation (RFA)</span>''' 
#'''<span style="color:#ff0000">Cryoablation</span>'''
#*'''Experience with renal cryosurgery predates that of RFA and has been more extensive'''
#* 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'''
*#* 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
*# '''Comparable cancer-specific and overall survival outcomes to partial nephrectomy, in select patients'''
* '''<span style="color:#ff0000">Disadvantage</span>'''
*# '''<span style="color:#ff0000">Risk of local recurrence after primary treatment is higher with TA</span>''' (3-10% cryoablation and 5-20% RFA) '''<span style="color:#ff0000">than partial</span>''' (0-3%) '''<span style="color:#ff0000">or radical nephrectomy</span>''' (0%)
*#* '''<span style="color:#ff0000">Local recurrence after TA can be salvaged with repeat TA.</span>'''
*#** '''<span style="color:#ff0000">Patients should be informed of higher risk of requiring secondary procedure</span>''', compared to partial nephrectomy
*#** '''<span style="color:#ff0000">Allowing for second treatment, risk of local recurrence of TA not significantly different than partial nephrectomy.</span>'''
*#* Observational study comparing partial nephrectomy to TA
*#** Design: retrospective cohort study
*#** Population: 1424 cT1a patients managed with partial nephrectomy or TA
*#** Results:
*#*** 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.
*#** [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.

==== <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>'''
*** 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.
***PN seems preferred over TA for cT1a: "PN should be prioritized in the management of patients with clinical T1a renal mass".

==== Contraindications ====
* '''Absolute'''
** '''Inaccessible tumour'''
** Large tumour
* '''Relative'''
** Completely intrarenal lesions or those immediately adjacent to the sinus or hilum are more difficult to treat effectively by TA

==== Technology ====
* '''RFA'''
** Utilizes high frequency alternating current (460-500 kHz) to induce ion agitation and frictional heating in adjacent tissue
*** Can be achieved through 2 types of radiofrequency generator systems:
***# Temperature-based system: drives the current to reach a target temperature
***# Impedance-based systems: continue ablation until a predetermined impedance level is reached.
* '''Cryoablation'''
** Generates lethal temperatures below -20 to -40 °C, resulting in coagulative tissue necrosis
** '''Volume of lethal temperature generated during cryoablation is regulated by (4):'''
**# '''Duration of freezing'''
**# '''Number of freeze cycles'''
**#* '''<span style="color:#ff0000">Double freeze results in larger volumes of renal tissue necrosis, compared to single freeze</span>'''
**# '''Size and number of cryoprobes'''
**# '''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
*** 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>'''
*'''Both radiofrequency ablation and cryoablation may be offered as options[https://pubmed.ncbi.nlm.nih.gov/28479239/]'''
*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

==== Technique ====
* TA for cystic lesions requires further investigation.
* '''<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/]'''
* Percutaneous approach is preferred over a surgical approach whenever feasible to minimize morbidity.
** 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 ====
* '''Cryoablation:'''
*# '''Renal fracture'''
*#* Higher risk when treating tumours >3cm
*# '''Hemorrhage'''
*# '''Adjacent organ injury'''
*# '''Ileus'''
*# '''Wound infection'''
* '''RFA (uncommon):'''
*# '''Acute renal failure'''
*# '''Stricture of the ureteropelvic junction'''
*# '''Necrotizing pancreatitis'''
*# '''Lumbar radiculopathy'''

==== 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.
* '''<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>'''
*** '''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>'''
* 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.

==== Recurrence following treatment ====
* '''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">Findings suggestive of local recurrence (5):</span>'''
*# '''<span style="color:#ff0000">Enhancement within the tumor bed beyond 6 months</span>'''
*# '''<span style="color:#ff0000">Progressive increase in size of an ablated neoplasm</span>'''
*# '''<span style="color:#ff0000">New nodularity in or around the treated zone</span>'''
*# '''<span style="color:#ff0000">Failure of the treated lesion to regress over time</span>'''
*# '''<span style="color:#ff0000">Satellite or port site lesions</span>'''
* '''<span style="color:#ff0000">Most local recurrences can be salvaged with repeat ablation</span>'''
** Some patients with progressive disease eventually require conventional surgery.
*** 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) ===

==== Advantages/Disadvantages ====
*'''<span style="color:#ff0000">Advantage (1):</span>'''
*# '''<span style="color:#ff0000">Preserved renal function compared to RN</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>'''
*#* A small proportion of patients to additional treatments (e.g. ureteral stents, abdominal drains, embolization of pseudoaneurysm).
*# '''<span style="color:#ff0000">Potential for hyperfiltration renal injury</span>'''
*#* Patients who undergo nephron-sparing surgery for RCC may be left with a relatively small amount of renal tissue and are at risk for development of long-term renal functional impairment from hyperfiltration renal injury
*#** '''<span style="color:#ff0000">Proteinuria is the initial manifestation</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>'''

==== Indications ====

===== 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">Absolute (3):</span>'''
**# '''<span style="color:#ff0000">Anatomic or functionally solitary kidney</span>'''
**# '''<span style="color:#ff0000">Bilateral tumors</span>'''
**# '''<span style="color:#ff0000">Known familial RCC syndrome</span>'''
** '''<span style="color:#ff0000">Relative (4):</span>'''
**# '''<span style="color:#ff0000">cT1a renal masses (preferred over TA and RN)</span>''', not managed with active surveillance
**# '''<span style="color:#ff0000">Pre-existing CKD</span>'''
**# '''<span style="color:#ff0000">Pre-existing proteinuria</span>'''
**# '''<span style="color:#ff0000">Young age</span>'''
**# '''<span style="color:#ff0000">Multifocal masses</span>'''
**# '''<span style="color:#ff0000">Comorbidities that are likely to impact future renal function, including (4):</span>'''
**## '''<span style="color:#ff0000">Moderate to severe hypertension</span>'''
**## '''<span style="color:#ff0000">Diabetes mellitus</span>'''
**## '''<span style="color:#ff0000">Recurrent urolithiasis</span>'''
**## '''<span style="color:#ff0000">Morbid obesity</span>'''

==== Approach ====
* Can be done via open/laparoscopic/robotic approach
** Pure or robot-assisted laparoscopic PN should be done by experienced surgeons
*A minimally invasive approach should be considered when it would not compromise oncologic, functional, and perioperative outcomes.[https://pubmed.ncbi.nlm.nih.gov/28479239/]
*See [[Open Kidney Surgery|Open Kidney Surgery Chapter Notes]]
*See [[Robotic Partial Nephrectomy|Robotic Partial Nephrectomy Chapter Notes]]

==== Technique ====
* '''Renal function can be optimized by (2):'''
*#'''Optimizing nephron mass preservation'''
*##'''<span style="color:#ff0000">The number of preserved nephrons is the primary factor determining renal function after PN</span>'''
*#'''Avoiding prolonged ischemia'''
*##'''<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
*'''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.'''
** Traditional PN is sharp excision with intentional removal of a modest rim of normal adjacent parenchyma
**Tumor enucleation refers to 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:[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) ===

==== Advantages/Disadvantages ====
*'''Advantages'''
*# '''Favorable perioperative outcomes compared to PN'''
*#* May reflect the high proportion of RN performed via the laparoscopic approach
*# '''Oncologic efficacy'''
* '''Disadvantage'''
** '''Associated with the greatest decrease in GFR''' and highest risk of de novo CKD stage 3 or higher.
*** 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

==== <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
* In observational studies, RN has been associated with increased CKD, worse overall survival, and cancer-specific survival compared to PN. The association with worse cancer-specific survival raises concerns about selection bias since PN should not theoretically be a more effective oncologic intervention than RN
* '''<span style="color:#ff00ff">EORTC 30904</span>'''
** '''Population: 541 patients with tumours <5cm suspicious for RCC (and normal contralateral kidney)'''
** '''Randomized to RN vs. PN'''
** '''Primary outcome: OS'''
** '''Secondary outcomes: CSS, cardiovascular events, renal function outcomes'''
** '''Results:'''
*** '''RN significantly improved OS'''
*** '''No difference in CSS (only 2% of patients died of cancer)'''
*** '''Cardiovascular deaths were less common in the RN group'''
*** '''RN favorable in terms of lower perioperative morbidity, while PN provided better renal functional outcomes'''
*** '''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
**[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.
** 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 primarily resulting from surgical removal of nephrons typically do not need further surgery, and might stabilize
* Despite the above, the following recommendations are made:
** '''<span style="color:#ff0000">PN is preferred over RN for small renal masses (T1a, <4.0 cm) whenever feasible</span>''' when intervention is indicated, because PN minimizes the risk of CKD or CKD progression and is associated with favorable oncologic outcomes, including excellent local control and RN represents gross overtreatment for most such lesions, which tend to have limited biologic potential
** Larger renal tumors (clinical stages T1b and T2) have increased oncologic potential and have often already replaced a substantial portion of the parenchyma, leaving less to be saved by PN. In the setting of a normal contralateral kidney, the relative merits of PN versus RN can be debated in this population.