Editing Renal Mass and Localized Renal Cancer (2021)

'''See [https://pubmed.ncbi.nlm.nih.gov/34115547/ Original Guidelines]'''

* Guidelines are relevant with literature up to October 2020
* Guideline focuses primarily on the evaluation and management of clinically localized sporadic renal masses suspicious for RCC in adults, including solid enhancing renal tumors and Bosniak 3 and 4 cystic renal masses.

== Diagnosis and Evaluation ==

=== Required ===
* '''<span style="color:#ff0000">History and physical</span>'''
* '''<span style="color:#ff0000">Imaging:</span>'''
** '''<span style="color:#ff0000">Regional: multiphase, cross-sectional abdominal imaging</span>'''
*** '''in ALL patients with a solid or complex cystic renal mass''' i.e. ultrasound alone is inadequate imaging of a solid or complex cystic renal mass
** '''<span style="color:#ff0000">Distant: chest x-ray</span>''' in patients with suspected renal malignancy
*** Not indicated in patients with suspected or confirmed benign renal masses
*** <span style="color:#ff0000">'''Indications for CT chest (3):'''</span>
***# <span style="color:#ff0000">'''Pulmonary symptoms'''</span>
***# <span style="color:#ff0000">'''Abnormal CXR'''</span>
***# <span style="color:#ff0000">'''High-risk disease, defined by (5):'''</span>
***##<span style="color:#ff0000">'''Presence of thrombi'''</span>
***##<span style="color:#ff0000">'''Presumed adenopathy'''</span>
***##<span style="color:#ff0000">'''Larger tumor size'''</span>
***##<span style="color:#ff0000">'''Infiltrative appearance'''</span>
***##<span style="color:#ff0000">'''Extensive tumor necrosis'''</span>
* '''<span style="color:#ff0000">Labs (3):</span>'''
*# '''<span style="color:#ff0000">CBC</span>'''
*# '''<span style="color:#ff0000">Urinalysis (including assessment of proteinuria)</span>'''
*# '''<span style="color:#ff0000">Comprehensive metabolic panel (electrolytes, liver function tests, assessment of GFR)</span>'''
*#; '''<span style="color:#ff0000">GFR and degree of proteinuria should be used assign CKD stage''' in patients with a solid or Bosniak 3/4 complex cystic renal mass, as this will influence management</span>
* '''<span style="color:#ff0000">Other</span>'''
**'''<span style="color:#ff0000">Referral for genetic counseling, if indicated</span>'''
*** '''<span style="color:#ff0000">Indications for genetic counseling (5):</span>'''
***# '''<span style="color:#ff0000">Age ≤ 46 years with renal malignancy</span>'''
***# '''<span style="color:#ff0000">Multifocal or bilateral renal masses</span>'''
***# '''<span style="color:#ff0000">Family history (first-or second-degree relative) with a history of renal malignancy</span>'''
***# '''<span style="color:#ff0000">Personal or family history suggests a familial RCC syndrome (even if kidney cancer has not been observed)</span>'''
***# '''<span style="color:#ff0000">Pathology demonstrates histologic findings suggestive of such a familial RCC syndrome</span>'''
***#* Hybrid oncocytic/chromophobe tumors are suggestive of BHD
** '''<span style="color:#ff0000">Referral to nephrology, if indicated</span>'''
*** '''<span style="color:#ff0000">Indications for referral to nephrology in a patient with a renal mass undergoing intervention (4):</span>'''
***# '''<span style="color:#ff0000">Estimated GFR < 45 mL/min/1.73m2</span>'''
***# '''<span style="color:#ff0000">Confirmed proteinuria</span>'''
***# '''<span style="color:#ff0000">Diabetics with pre-existing CKD</span>'''
***# '''<span style="color:#ff0000">When eGFR is expected to be <30 mL/min/1.73m2 after intervention</span>'''

=== Optional ===
* '''<span style="color:#ff0000">Renal mass biopsy</span>'''
** Generally safe with low risk of significant complications (bleeding) and no reported cases of tumor seeding using contemporary techniques.
** A diagnosis of malignancy or renal cell carcinoma on renal mass biopsy is highly reliable.
*** Pooled sensitivity: 96.7%
*** Pooled positive predictive value: 98.8%
*** Pooled specificity: 94.4%
** '''Potential limitations of RMB include (4):'''
**# '''A benign biopsy must be distinguished from a non-diagnostic biopsy (renal parenchyma or connective tissues) result.'''
**#* Non-diagnostic rate of renal mass biopsy is approximately 14%, which can be substantially reduced with repeat biopsy
**# '''A benign biopsy may not always correlate with benign histology.'''
**#* Pooled negative predictive value: 80.8%
**#*Due to the imperfect nature of renal mass biopsy, patients with benign renal mass biopsy may warrant follow-up.
**# '''Grade concordance from biopsy to surgically resected tissue is imperfect.'''
**# '''Oncocytic neoplasms may represent a diagnostic dilemma.'''
** '''<span style="color:#ff0000">Indications</span>'''
***'''<span style="color:#ff0000">Consider biopsy when a mass is suspected to be hematologic, metastatic, inflammatory, or infectious.</span>'''
*** '''<span style="color:#ff0000">Should be obtained if it will influence management</span>'''
**** '''<span style="color:#ff0000">NOT required for (2):</span>'''
****# '''<span style="color:#ff0000">Young or healthy patients who are unwilling to accept the uncertainties associated with RMB</span>'''
****# '''<span style="color:#ff0000">Older or frail patients who will be managed conservatively independent of RMB findings</span>'''
***'''<span style="color:#ff0000">Biopsy or aspiration of cystic renal masses is generally not recommended, due to (2):</span>'''
***#'''<span style="color:#ff0000">Concerns regarding tumor spillage</span>'''
***#'''<span style="color:#ff0000">High likelihood of obtaining a non-informative result due to sampling error</span>'''
**For biopsy of solid renal mass, multiple core biopsies should be obtained and are preferred over fine needle aspiration.

== Management ==

=== Counseling ===
* Discuss malignant potential based on imaging characteristics such as tumor size/complexity, histology (if available), etc.
** Low risk of mortality secondary to cT1a tumors should be described
* Discuss potential effect of intervention on risk of chronic kidney disease (CKD), dialysis, and survival.

=== Options ===
# '''Nephrectomy''' (partial vs. radical)
# '''Thermal ablation''' (radiofrequency vs. cryoablation)
# '''Active surveillance'''

==== Nephrectomy ====
*'''<span style="color:#ff0000">Partial nephrectomy</span>'''
** '''<span style="color:#ff0000">Indications</span>''' (when intervention is necessary for solid or Bosniak 3/4 complex cystic renal mass)
*** '''<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 (6):</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>'''
** Surgical considerations
*** Renal function can be optimized by (2):
***# Optimizing nephron mass preservation
***# Avoiding prolonged ischemia
*** Negative surgical margins should be prioritized
**** Extent of normal parenchyma removed should consider the clinical situation and tumor characteristics, including growth pattern, and interface with normal tissue.
***** '''To optimize parenchymal mass preservation, tumor enucleation should be considered in patients with:'''
*****# '''Familial RCC syndromes'''
*****#* '''Aggressive RCC syndromes, such as HLRCC, should be best managed with wide margin PN or RN.'''
*****# '''Multifocal disease'''
*****# '''Severe CKD'''
*'''<span style="color:#ff0000">Radical nephrectomy</span>'''
** '''<span style="color:#ff0000">Indication (1)</span>''' (when intervention is necessary for solid or Bosniak 3/4 complex cystic renal mass):
**# '''<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>'''
**#* '''<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.
*'''<span style="color:#ff0000">Lymphadenectomy'''
** '''<span style="color:#ff0000">Indications (1):</span>'''
**#'''<span style="color:#ff0000">Clinically concerning regional lymphadenopathy (for staging purposes)</span>'''
*'''<span style="color:#ff0000">Adrenalectomy</span>'''
** '''<span style="color:#ff0000">Indications</span>'''
***'''<span style="color:#ff0000">Absolute (1):</span>'''
***# '''<span style="color:#ff0000">If preoperative imaging or intraoperative inspection suggests metastasis or adrenal enlargement</span>'''
***#* One exception is when patient has a well-characterized adenoma, which may not mandate surgical excision
*** '''<span style="color:#ff0000">Relative (1):</span>'''
***# '''<span style="color:#ff0000">Locally advanced features are identified preoperatively or during exploration and the gland is in close proximity to the tumour</span>'''
***#* 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.
*Approach
** A minimally invasive approach should be considered when it would not compromise oncologic, functional, and perioperative outcomes.
*'''Other considerations'''
** Adjacent renal parenchyma in the nephrectomy specimen should be evaluated for possible intrinsic renal disease, particularly for patients with CKD or risk factors for developing CKD.
** '''Consider referral to medical oncology when there is concern for (2):'''
**# '''Metastasis'''
**# '''Incompletely resected disease'''

==== Thermal ablation (TA) ====
* '''<span style="color:#ff0000">Indications</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.
* Approach
**Percutaneous is preferred over surgical approach, whenever feasible, to minimize morbidity.
* Modality
** Both radiofrequency ablation and cryoablation may be offered as options
* '''Other considerations'''
**'''Biopsy should be performed prior to (preferred) or at the time of ablation''' to provide pathologic diagnosis and guide subsequent surveillance.

==== Active surveillance (AS) ====
* '''<span style="color:#ff0000">Indications'''
** '''<span style="color:#ff0000">Absolute (1):'''
**# '''<span style="color:#ff0000">Risk of intervention/competing risks of death outweighs the potential benefits of intervention'''
** '''<span style="color:#ff0000">Relative (9):'''
*** '''<span style="color:#ff0000">Tumour factors (2)'''
***# '''<span style="color:#ff0000">Solid renal mass < 2cm'''
***#*'''<span style="color:#ff0000">In patients with familial RCC syndromes, tumours can be observed if <3 cm as the risk of metastases remains low in this setting</span>'''
***#** '''<span style="color:#ff0000">HLRCC and succinate dehydrogenase deficiency RCC are the exception as tumors in these syndromes are often very aggressive.</span>'''
***# '''<span style="color:#ff0000">Complex but predominantly cystic renal masses'''
*** '''<span style="color:#ff0000">Patient factors (7)'''
***# '''<span style="color:#ff0000">Elderly'''
***# '''<span style="color:#ff0000">Life expectancy < 5 years'''
***# '''<span style="color:#ff0000">High calculated comorbidities'''
***# '''<span style="color:#ff0000">Excessive perioperative risk'''
***# '''<span style="color:#ff0000">Poor functional status'''
***# '''<span style="color:#ff0000">Marginal renal function (≥CKD3b)'''
***# '''<span style="color:#ff0000">Patient preference'''
***#* 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.
***#** 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.
* '''<span style="color:#ff0000">In patients undergoing AS, periodic clinical surveillance and/or imaging is recommended in asymptomatic patients</span>'''
** '''Frequency and intensity are tailored to patient-risk,''' based on tumour size, tumor complexity, infiltrative appearance and median growth
***'''Patients with no prior imaging should have surveillance imaging initially every 3 to 6 months'''
*** Preferred modality is not well established, but initial imaging should preferably consist of contrast-enhanced cross-sectional imaging.
*** '''Chest x-ray is warranted annually or if intervention triggers are encountered or symptoms arise.'''
* '''<span style="color:#ff0000">Indications for "intervention" (treatment or increased AS intensity) (5):</span>[https://www.auanet.org/documents/Guidelines/PDF/RCC-Active-Surveillance-Algorithm.pdf §]:'''
*# '''<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)

== Follow-up ==

=== Counseling ===
* Discuss the implications of stage, grade, and histology including the risks of recurrence and possible sequelae of treatment.

=== Treated malignant renal masses ===

==== Investigations ====

*'''History and physical exam'''
* '''Laboratory (2):'''
*# '''Serum creatinine, eGFR'''
*# '''Urinalysis'''
** 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.
** 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
** Patients found to have progressive renal insufficiency or proteinuria should be referred to nephrology
* '''Imaging'''
** '''Regional'''
*** '''Abdominal imaging'''
**** '''CT or MRI pre- and post-intravenous contrast preferred'''
**** See schedule below
** '''Distant'''
*** '''Chest'''
**** See schedule below
*** Bone scan
**** Not indicated in routine follow-up of treated malignant renal mass
**** Indications (3):
****# Bone pain
****# Elevated alkaline phosphatase
****# Radiographic findings suggestive of a bony neoplasm
*** CT/MRI brain and/or spine
**** Not indicated in routine follow-up of treated malignant renal mass
**** Indication (1):
****# Acute neurological signs or symptoms
** Other
*** 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.
** '''Patients with findings suggesting a new renal primary or local recurrence of renal malignancy should undergo metastatic evaluation including chest and abdominal imaging.'''

==== Follow-up schedule ====

===== Nephrectomy =====
* '''<span style="color:#ff0000">Risk-stratified into (4):'''
*# '''<span style="color:#ff0000">Low-risk: pT1 and Grade 1/2'''
*# '''<span style="color:#ff0000">Intermediate-risk: pT1 and Grade 3/4, or pT2 any Grade'''
*# '''<span style="color:#ff0000">High-risk: pT3 any Grade'''
*# '''<span style="color:#ff0000">Very high-risk: pT4 or pN1, or sarcomatoid/rhabdoid dedifferentiation, or macroscopic positive margin'''
** '''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.
* '''<span style="color:#ff0000">Follow-up based on risk stratification'''
** '''<span style="color:#ff0000">See [https://www.auanet.org/documents/Guidelines/PDF/RCC-Follow-Up-Algorithm.pdf Table 1] from original guidelines'''
***'''<span style="color:#ff0000">If low-risk, abdominal and chest imaging at 12, 24, 48 and 60 months'''
***'''<span style="color:#ff0000">If intermediate-risk, abdominal and chest imaging at 6, 12, 24, 36, 48 and 60 months'''
* '''Imaging:'''
** '''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.'''
*** '''After 5 years, informed/shared decision-making should dictate further abdominal imaging.'''
** '''Chest'''
*** '''Modality'''
**** '''Chest x-ray low- and intermediate-risk groups'''
**** '''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.'''

===== Thermal ablation =====
* '''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 [https://www.auanet.org/documents/Guidelines/PDF/RCC-Follow-Up-Algorithm.pdf Table 1] from original guidelines)'''

==== Management of recurrence ====
* Patients with findings suggestive of metastatic renal malignancy should be evaluated to define the extent of disease and referred to medical oncology.
* Surgical resection or ablative therapies may be considered in select patients with isolated (ipsilateral kidney and/or retroperitoneum) or oligo-metastatic disease.

=== Pathologically-proven benign renal masses ===
* Occasional clinical and laboratory evaluation for sequelae of treatment; most do not require routine periodic imaging.

== References ==

* Campbell, Steven C., et al. "Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-Up: AUA Guideline Part I." ''The Journal of urology'' (2021): 10-1097.