Editing Management of Localized and Locally Advanced Disease (section)

=== 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