Kidney Cancer: Diagnosis and Evaluation: Difference between revisions

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[[Category:Kidney Cancer]]
[[Category:Kidney Cancer]]
'''See [[Renal Mass and Localized Renal Cancer (2021)|2021 AUA Renal Mass and Localized RCC Guideline Notes]]'''


'''Includes 2013 CUA Guidelines on Genetic Screening for Hereditary Renal Cell Cancers and parts from 2014 CUA Surgical Management of Renal Cell Carcinoma Consensus Statement and 2021 AUA Renal Mass and Localized RCC Guidelines'''
'''Includes 2013 CUA Guidelines on Genetic Screening for Hereditary Renal Cell Cancers and parts from 2014 CUA Surgical Management of Renal Cell Carcinoma Consensus Statement and 2021 AUA Renal Mass and Localized RCC Guidelines'''
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**'''<span style="color:#ff0000">History and physical exam</span>'''
**'''<span style="color:#ff0000">History and physical exam</span>'''
** '''<span style="color:#ff0000">Labs:</span>'''
** '''<span style="color:#ff0000">Labs:</span>'''
*** '''<span style="color:#ff0000">CUA: CBC, Cr, AST/ALT (markers of liver dysfunction), ALP, corrected calcium (markers of bone dysfunction)</span>'''
*** '''<span style="color:#ff0000">AUA (5):</span>'''
**** '''<span style="color:#ff0000">Urine cytology in central tumours</span>'''
**** '''Markers of prognosis in advanced disease (Motzer/Heng criteria, see Advanced Kidney Cancer Chapter Notes)'''
*** '''<span style="color:#ff0000">AUA:</span>'''
***# '''<span style="color:#ff0000">CBC</span>'''
***# '''<span style="color:#ff0000">CBC</span>'''
***# '''<span style="color:#ff0000">Urinalysis (including assessment of proteinuria)</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">Serum electrolytes</span>'''
***#'''<span style="color:#ff0000">Liver function tests</span>'''
***#'''<span style="color:#ff0000">Assessment of GFR</span>'''
***'''<span style="color:#ff0000">CUA: CBC, Cr, AST/ALT (markers of liver dysfunction), ALP, corrected calcium (markers of bone dysfunction)</span>'''
**** '''<span style="color:#ff0000">Urine cytology in central tumours</span>'''
**** '''Markers of prognosis in advanced disease (Motzer/Heng criteria, see [[Metastatic Kidney Cancer|Advanced Kidney Cancer Chapter Notes]])'''
** '''<span style="color:#ff0000">Imaging:</span>'''
** '''<span style="color:#ff0000">Imaging:</span>'''
*** '''<span style="color:#ff0000">Primary tumour</span>'''
*** '''<span style="color:#ff0000">Primary tumour</span>'''
**** '''<span style="color:#ff0000">CUA:</span>'''
**** '''<span style="color:#ff0000">AUA:</span>'''
***** '''<span style="color:#ff0000">Multiphase CT or MRI</span>'''
****'''<span style="color:#ff0000">CUA:</span>'''
***** '''<span style="color:#ff0000">Triphasic CT abdomen/pelvis</span>'''
***** '''<span style="color:#ff0000">Triphasic CT abdomen/pelvis</span>'''
****** '''MRI if CT contraindicated''' (pregnant/allergy/CKD)
****** '''MRI if CT contraindicated''' (pregnant/allergy/CKD)
****** '''If thrombus present, consider doppler US/MRI to stage IVC involvement'''
****** '''If thrombus present, consider doppler US/MRI to stage IVC involvement'''
*** '''<span style="color:#ff0000">Metastasis:</span>'''
**** '''<span style="color:#ff0000">AUA:</span>'''
**** '''<span style="color:#ff0000">AUA:</span>'''
***** '''<span style="color:#ff0000">Multiphase CT or MRI</span>'''
***** '''<span style="color:#ff0000">CXR</span>'''
*** '''<span style="color:#ff0000">Metastasis:</span>'''
****** '''<span style="color:#ff0000">Indications for CT chest (3):</span>'''
**** '''<span style="color:#ff0000">CUA:</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">CUA:</span>'''
***** '''<span style="color:#ff0000">CXR, consider CT chest if ≥stage T2</span>'''
***** '''<span style="color:#ff0000">CXR, consider CT chest if ≥stage T2</span>'''
***** '''Bone scan, if clinically indicated or elevated alkaline phosphatase and serum calcium'''
***** '''Bone scan, if clinically indicated or elevated alkaline phosphatase and serum calcium'''
***** '''Brain CT or MRI if large volume metastatic disease'''
***** '''Brain CT or MRI if large volume metastatic disease'''
**** '''<span style="color:#ff0000">AUA:</span>'''
***** '''<span style="color:#ff0000">CXR</span>'''
****** '''Indications for CT chest (3)§:'''
******# '''Pulmonary symptoms'''
******# '''Abnormal CXR'''
******# '''High-risk disease'''
** '''<span style="color:#ff0000">Other:</span>'''
** '''<span style="color:#ff0000">Other:</span>'''
*** '''<span style="color:#ff0000">Renal mass biopsy</span>'''
*** '''<span style="color:#ff0000">Renal mass biopsy</span>'''
*** '''<span style="color:#ff0000">Genetic counseling</span>'''
*** '''<span style="color:#ff0000">Genetic counseling, if indicated</span>'''
***'''<span style="color:#ff0000">Referral to nephrology, if indicated</span>'''


== History and Physical exam ==
== History and Physical Exam ==


* '''History'''
=== History ===
** '''Recall risk factors for RCC''': smoking, hypertension, obesity, familial syndromes, CKD
* '''<span style="color:#ff0000">Risk factors for RCC</span>''': smoking, hypertension, obesity, familial syndromes, CKD
** '''Most (>50%) of renal masses are diagnosed incidentally during an evaluation for unrelated signs or symptoms.'''
*'''<span style="color:#ff0000">Family history</span>'''
*'''<span style="color:#ff0000">Symptoms</span>'''
**'''<span style="color:#ff0000">Most (>50%) of renal masses are diagnosed incidentally</span> during an evaluation for unrelated signs or symptoms.'''
*** '''Many remain asymptomatic and nonpalpable until they are locally advanced'''
*** '''Many remain asymptomatic and nonpalpable until they are locally advanced'''
**** Flank pain is usually due to hemorrhage and clot obstruction, but can also occur with locally advanced or invasive disease.
**** Flank pain is usually due to hemorrhage and clot obstruction, but can also occur with locally advanced or invasive disease.
*** The “classic triad” of symptoms associated with a malignant renal mass was hematuria, flank pain and abdominal mass
*** The “classic triad” of symptoms associated with a malignant renal mass was hematuria, flank pain and abdominal mass
****<5% of patients in contemporary series present with these symptoms
****<5% of patients in contemporary series present with these symptoms
** '''Locally advanced RCC usually presents with pain''', generally from invasion of the posterior abdominal wall, nerve roots, or paraspinous muscles.
*** '''<span style="color:#ff0000">Symptoms of advanced disease:</span>'''
** '''Symptoms of advanced disease include flank pain, gross hematuria, constitutional symptoms such as weight loss, fever, and night sweats'''
****'''<span style="color:#ff0000">Flank pain</span>'''
** New onset coughing or other respiratory issues may suggest pulmonary metastases
*****Locally advanced RCC usually presents with pain, generally from invasion of the posterior abdominal wall, nerve roots, or paraspinous muscles.
** New neurologic symptoms may suggest cerebral metastases
****'''<span style="color:#ff0000">Gross hematuria</span>'''
** '''Spontaneous perirenal hemorrhage is an uncommon presentation of RCC in which the underlying mass may be obscured. Repeat CT a few months later can provide a definitive diagnosis.'''
****'''<span style="color:#ff0000">Constitutional symptoms such as weight loss, fever, and night sweats</span>'''
* '''Physical examination'''
*** New onset coughing or other respiratory issues may suggest pulmonary metastases
** Limited role in clinically localized disease but may reveal
*** New neurologic symptoms may suggest cerebral metastases
*** Unsuspected adenopathy, varicocele
* '''Spontaneous perirenal hemorrhage is an uncommon presentation of RCC in which the underlying mass may be obscured. Repeat CT a few months later can provide a definitive diagnosis.'''
*** Medical conditions that influence management decisions including body habitus, prior abdominal scars, stigmata of CKD, etc.
 
*** Findings suggestive of familial RCC syndrome, such as dermatologic lesions
=== Physical Examination ===
** Blood pressure and performance status should be assessed
* '''<span style="color:#ff0000">General'''
** Neurologic exam should be performed if there is any suggestion of cerebral or spinal metastases
**'''<span style="color:#ff0000">Blood pressure'''
** '''Findings suggestive of advanced disease (5):'''
**'''<span style="color:#ff0000">Performance status'''
**# '''Palpable abdominal mass'''
**'''<span style="color:#ff0000">Body habitus'''
**# '''Nonreducing varicocele'''
**'''<span style="color:#ff0000">Dermatologic lesions</span>,''' which may suggest a familial RCC syndrome
**# '''Right-sided varicocele'''
*'''<span style="color:#ff0000">Lymphadenopathy'''
**# '''Bilateral lower extremity edema resulting from venous involvement'''
**'''<span style="color:#ff0000">Cervical/supraclavicular'''
**# '''Palpable cervical lymphadenopathy'''
**'''<span style="color:#ff0000">Axillary'''
* '''Paraneoplastic syndromes in RCC'''
**'''<span style="color:#ff0000">Groin'''
** '''Found in 10-20% of patients with metastatic RCC (NEW-HALF-CAP):'''
*'''<span style="color:#ff0000">Abdomen'''
**# '''Neuropathy''' (3%)
**'''<span style="color:#ff0000">Prior abdominal scars'''
**# '''Elevated ESR''' '''(56%, most common)'''
*'''<span style="color:#ff0000">Genitals'''
**# '''Weight loss''' (34%)
**'''<span style="color:#ff0000">Scrotum'''
**# '''Hypertension''' (38%)
***'''<span style="color:#ff0000">Varicocele'''
**#* Can be due to elevated renin production by tumour, compression of renal artery, or AV fistula in tumour
* '''<span style="color:#ff0000">Extremities'''
**# '''Anemia''' (36%)
**<span style="color:#ff0000">'''Lower extremity edema'''
**# '''Elevated LFTs''' (14%)
*'''<span style="color:#ff0000">Neurologic exam'''
**#* Due to nonmetastatic hepatic dysfunction, also known as Stauffer syndrome
**Should be performed if there is any suggestion of cerebral or spinal metastases
**# '''Fever''' (17%)
* Limited role in clinically localized disease
**# '''HyperCalcemia''' (5%)
*'''<span style="color:#ff0000">Physical exam findings suggestive of advanced disease (5):</span>'''
**#* Can be due to (2):
*# '''<span style="color:#ff0000">Palpable abdominal mass</span>'''
**#*# Paraneoplastic phenomena (production of PTH-related protein)
*# '''<span style="color:#ff0000">Nonreducing varicocele</span>'''
**#*# Osteolytic metastatic involvement of the bone
*# '''<span style="color:#ff0000">Right-sided varicocele</span>'''
**#* '''Signs and symptoms include nausea, anorexia, fatigue, and decreased deep tendon reflexes'''
*# '''<span style="color:#ff0000">Bilateral lower extremity edema resulting from venous involvement</span>'''
**#* '''Management includes vigorous hydration followed by diuresis with furosemide and the selective use of bisphosphonates (if adequate renal function),''' corticosteroids or calcitonin
*# '''<span style="color:#ff0000">Palpable cervical lymphadenopathy</span>'''
**# '''Amyloidosis''' (2%)
 
**# '''Polycythemia''' (4%)
=== Paraneoplastic syndromes in RCC ===
** '''Management'''
* '''Found in 10-20% of patients with metastatic RCC (<span style="color:#0000ff">NEW-HALF-CAP</span>):'''
*** '''Treatment of paraneoplastic syndromes has required surgical excision or systemic therapy''' and, except for hypercalcemia, medical therapies have not proved helpful.
*# '''<span style="color:#0000ff">N</span><span style="color:#ff0000">europathy</span>''' (3%)
*# '''<span style="color:#0000ff">E</span><span style="color:#ff0000">levated ESR </span>(56%, most common)'''
*# '''<span style="color:#0000ff">W</span><span style="color:#ff0000">eight loss</span>''' (34%)
*# '''<span style="color:#0000ff">H</span><span style="color:#ff0000">ypertension</span>''' (38%)
*#* Can be due to elevated renin production by tumour, compression of renal artery, or AV fistula in tumour
*# '''<span style="color:#0000ff">A</span><span style="color:#ff0000">nemia</span>''' (36%)
*# '''<span style="color:#ff0000">Elevated </span><span style="color:#0000ff">L</span><span style="color:#ff0000">FTs''' (14%)
*#* Due to nonmetastatic hepatic dysfunction, also known as Stauffer syndrome
*# '''<span style="color:#0000ff">F</span><span style="color:#ff0000">ever</span>''' (17%)
*# '''<span style="color:#ff0000">Hyper</span><span style="color:#0000ff">C<span style="color:#ff0000">alcemia</span>''' (5%)
*#* Can be due to (2):
*#*# Paraneoplastic phenomena (production of PTH-related protein)
*#*# Osteolytic metastatic involvement of the bone
*#* '''Signs and symptoms include nausea, anorexia, fatigue, and decreased deep tendon reflexes'''
*#* '''Management includes vigorous hydration followed by diuresis with furosemide and the selective use of bisphosphonates (if adequate renal function),''' corticosteroids or calcitonin
*# '''<span style="color:#0000ff">A</span><span style="color:#ff0000">myloidosis</span>''' (2%)
*# '''<span style="color:#0000ff">P</span><span style="color:#ff0000">olycythemia</span>''' (4%)
* '''Management'''
** '''Treatment of paraneoplastic syndromes has required surgical excision or systemic therapy''' and, except for hypercalcemia, medical therapies have not proved helpful.


== Labs ==
== Labs ==


* There are no biomarkers or routine laboratory tests used to diagnose renal malignancies.
* There are no biomarkers or routine laboratory tests used to diagnose renal malignancies.
* '''Recommended laboratory investigations in a patient with suspected RCC:'''
** '''2014 CUA Surgical Management of Renal Cell Carcinoma Consensus Statement (4):'''
**# '''CBC'''
**# '''Cr'''
**# '''Markers of liver dysfunction (transaminases)'''
**# '''Markers of bone dysfunction (ALP and corrected calcium)'''
** '''2021 AUA:'''
**# '''CBC'''
**# '''Urinalysis (including assessment of proteinuria)'''
**# '''Comprehensive metabolic panel (electrolytes, liver function tests, assessment of GFR)'''
*** CBC should be considered prior to any intervention
*** Urinalysis with dipstick and microscopic evaluation should be obtained to assess for proteinuria, hematuria, pyuria or signs of other genitourinary maladies.
**** Presence of proteinuria is an important prognostic indicator and can be detected by standard urine dipstick.
***** Patients with a positive dipstick test (1+ or greater) should undergo confirmation by a quantitative measurement (protein-to-creatinine ratio or albumin-to-creatinine ratio), as part of a focused medical workup for renal dysfunction.
**** Microscopic hematuria should also be further assessed to rule out a co-existing urinary tract conditions
*** The comprehensive metabolic panel should be reviewed for electrolyte abnormalities and hepatic functional parameters.
**** Abnormalities in hepatic function may prompt further workup to exclude co-existing hepatic disease or metastases which may impact management or overall prognosis
**** Elevated ALP and/or bone pain should prompt investigation of potential bone metastases
*** '''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
**** Proper classification of CKD is outlined in the Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines, which takes into account (3):
****# GFR (CKD-EPI GFR equation)
****# Proteinuria
****# Etiology of CKD
**** '''<span style="color:#ff0000">Indications for referral to nephrology in a patient with a renal mass (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>'''


=== Recommended laboratory investigations in a patient with suspected RCC ===
==== AUA ====
*'''[https://pubmed.ncbi.nlm.nih.gov/28479239/ 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer]'''
*#'''<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>'''
** CBC should be considered prior to any intervention
** Urinalysis with dipstick and microscopic evaluation should be obtained to assess for proteinuria, hematuria, pyuria or signs of other genitourinary maladies.
*** Presence of proteinuria is an important prognostic indicator and can be detected by standard urine dipstick.
**** Patients with a positive dipstick test (1+ or greater) should undergo confirmation by a quantitative measurement (protein-to-creatinine ratio or albumin-to-creatinine ratio), as part of a focused medical workup for renal dysfunction.
*** Microscopic hematuria should also be further assessed to rule out a co-existing urinary tract conditions
** The comprehensive metabolic panel should be reviewed for electrolyte abnormalities and hepatic functional parameters.
*** Abnormalities in hepatic function may prompt further workup to exclude co-existing hepatic disease or metastases which may impact management or overall prognosis
*** Elevated ALP and/or bone pain should prompt investigation of potential bone metastases
** '''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'''
*** Proper classification of CKD is outlined in the Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines, which takes into account (3):
***# GFR (CKD-EPI GFR equation)
***# Proteinuria
***# Etiology of CKD
*** '''<span style="color:#ff0000">Indications for referral to nephrology in a patient with a renal mass (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>'''
==== CUA ====
*'''2014 CUA Surgical Management of Renal Cell Carcinoma Consensus Statement (4):'''
*# '''CBC'''
*# '''Cr'''
*# '''Markers of liver dysfunction (transaminases)'''
*# '''Markers of bone dysfunction (ALP and corrected calcium)'''
== Imaging ==
== Imaging ==


=== Primary ===
=== Primary ===


* '''<span style="color:#ff0000">Radiologic classification of renal masses</span>''' (see CW Box 57-2):
* '''<span style="color:#ff0000">Radiologic classification of renal masses</span>'''
** '''<span style="color:#ff0000">Cystic</span>'''
** '''<span style="color:#ff0000">Cystic</span>'''
*** '''<span style="color:#ff0000">Simple vs. Complex</span>'''
*** '''<span style="color:#ff0000">Simple vs. Complex</span>'''
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*'''Goals of imaging are to evaluate (4):'''
*'''Goals of imaging are to evaluate (4):'''
*# '''Renal mass characteristics'''
*# '''Renal mass characteristics'''
*#* Tumor complexity
*#* Tumor size
*#**Size is inversely correlated with risk of malignancy
*#***Proportion of surgically resected masses found to be benign[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734327/]
*#****<2cm: 25%
*#****<4cm: 19%
*#*Tumor complexity
*#* Degree of contrast enhancement
*#* Degree of contrast enhancement
*#* Presence or absence of fat
*#* Presence or absence of fat
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==== CT ====
==== CT ====
* '''IV contrast'''
 
** '''Contraindications (2):'''
* '''Contrast-enhanced CT is the modality of choice in evaluating cystic renal masses.[https://pubmed.ncbi.nlm.nih.gov/31900669/]'''
**# '''Severe allergy'''
**'''MRI is used when CT is contraindicated''' (e.g., patients with allergy to iodinated contrast agent) or as a problem-solving modality for equivocal findings. MRI can show some septa that are less apparent at CT and demonstrate definitive enhancement in those cysts that show only equivocal enhancement at CT. As a consequence, renal cysts can be placed in a higher Bosniak category with MRI than with CT'''[https://pubmed.ncbi.nlm.nih.gov/31900669/]'''
**# '''Severe chronic kidney disease'''
 
*** '''Non-contrast CT, MRI and US (with Doppler) can be used to characterize renal masses in patients who cannot receive intravenous contrast'''
===== IV contrast =====
** '''Contrast-induced nephropathy'''
 
*** '''Due to intrarenal vasoconstriction and tubular necrosis'''
*'''<span style="color:#ff0000">Contraindications (2):'''
*** '''Risk factors'''
*# '''<span style="color:#ff0000">Severe allergy'''
***# '''Diabetes mellitus'''
*# '''<span style="color:#ff0000">Severe chronic kidney disease'''
***# '''Advanced age'''
** '''<span style="color:#ff0000">Patients with GFR <45 ml/min/1.73m2 should receive contrast with caution</span>'''
***# '''Congestive heart failure'''
*** '''Patients with acute kidney injury or GFR < 30 mL/min/1.73m2 who are not undergoing renal replacement therapy should receive intravenous normal saline prophylaxis prior to receiving iodinated contrast media[https://pubmed.ncbi.nlm.nih.gov/34115547/ §].'''
***# '''Hypertension'''
*** '''Patients with GFR 30-44 mL/min/1.73m2 may be considered for intravenous fluid prophylaxis per individual physician discretion based on the patient’s risk factor for renal injury[https://pubmed.ncbi.nlm.nih.gov/34115547/ §].'''
***# '''Dehydration'''
**** '''MRI with second generation gadolinium-based intravenous contrast is now a safer option in many patients with severe CKD'''
***# '''Diuretic use'''
**'''In patients who cannot receive intravenous contrast, MRI, non-contrast CT, and US (with Doppler) can be used to characterize renal masses'''  
***# '''Low hematocrit'''
*'''<span style="color:#ff0000">Contrast-induced nephropathy'''
***# '''Ventricular ejection fraction < 40%'''
** '''Due to intrarenal vasoconstriction and tubular necrosis'''
***# '''Concomitant exposure to chemotherapy, aminoglycoside or nonsteroidal anti-inflammatory agents'''
** '''<span style="color:#ff0000">Risk factors'''
***# '''Hyperuricemia'''
**# '''<span style="color:#ff0000">Diabetes mellitus'''
***# '''Diseases that affect renal hemodynamics, such as end-stage liver disease and nephrotic syndrome'''
**# '''<span style="color:#ff0000">Advanced age'''
***# '''Patients with a diagnosis of a paraproteinemia syndrome/disease (e.g., multiple myeloma), history of a kidney transplant, renal tumor, renal surgery, or single kidney may also be at higher risk'''
**# '''<span style="color:#ff0000">Congestive heart failure'''
**** '''The patients at highest risk for developing CIN are those with both diabetes and pre-existing renal insufficiency.'''
**# '''<span style="color:#ff0000">Hypertension'''
*** '''Metformin'''
**# '''<span style="color:#ff0000">Dehydration'''
**** '''Patients with type 2 diabetes mellitus receiving metformin may have an accumulation of the drug after administering intravascular radiologic contrast medium (IRCM), resulting in biguanide lactic acidosis'''
**# '''<span style="color:#ff0000">Diuretic use'''
**** '''Biguanide lactic acidosis'''
**# '''<span style="color:#ff0000">Low hematocrit'''
***** Symptoms of include vomiting, diarrhea, and somnolence
**# '''<span style="color:#ff0000">Ventricular ejection fraction < 40%'''
***** Fatal in ≈50% of cases
**# '''<span style="color:#ff0000">Concomitant exposure to chemotherapy, aminoglycoside or nonsteroidal anti-inflammatory agents'''
***** '''Rare in patients with normal renal function (no defined threshold but some studies suggest <60).'''
**# '''<span style="color:#ff0000">Hyperuricemia'''
****** '''In patients with normal renal function and no known comorbidities there is no need to discontinue metformin before IRCM use, nor is there a need to check creatinine following the imaging study.'''
**# '''Diseases that affect renal hemodynamics, such as end-stage liver disease and nephrotic syndrome'''
****** '''In patients with renal insufficiency metformin should be discontinued the day of the study and withheld for 48 hours.''' Post-procedure creatinine should be measured at 48 hours and metformin started once kidney function is normal.
**# '''Patients with a diagnosis of a paraproteinemia syndrome/disease (e.g., multiple myeloma), history of a kidney transplant, renal tumor, renal surgery, or single kidney may also be at higher risk'''
***** It is not necessary to discontinue metformin before gadolinium-enhanced MRI studies when the amount of gadolinium administered is in the usual dosage range of 0.1 to 0.3 mmol per kilogram of body weight.
*** '''The patients at highest risk for developing CIN are those with both diabetes and pre-existing renal insufficiency.'''
**** Prevention of CIN is of great concern and has been a subject of many different studies. Hydration is the major preventative action against CIN. Periprocedural IV hydration with 0.9% saline at 100 mL/hr 12 hours before to 12 hours after has been shown to decrease the incidence of CIN after IV contrast use
** '''<span style="color:#ff0000">Metformin'''
** '''Patients with GFR <45 ml/min/1.73m2 should receive contrast with caution'''
*** '''Patients with type 2 diabetes mellitus receiving metformin may have an accumulation of the drug after administering intravascular radiologic contrast medium (IRCM), resulting in biguanide lactic acidosis'''
*** '''Patients with acute kidney injury or GFR < 30 mL/min/1.73m2 who are not undergoing renal replacement therapy should receive intravenous normal saline prophylaxis prior to receiving iodinated contrast media§.'''
*** '''Biguanide lactic acidosis'''
*** '''Patients with GFR 30-44 mL/min/1.73m2 may be considered for intravenous fluid prophylaxis per individual physician discretion based on the patient’s risk factor for renal injury§.'''
**** Symptoms of include vomiting, diarrhea, and somnolence
**** MRI with second generation gadolinium-based intravenous contrast is now a safer option in many patients with severe CKD
**** Fatal in ≈50% of cases
* '''Enhancement'''
**** '''Rare in patients with normal renal function (no defined threshold but some studies suggest <60).'''
** <span style="color:#ff0000">Hounsfield units (HU) are a standardized quantitative measurement of x-ray attenuation</span>[https://pubmed.ncbi.nlm.nih.gov/29362150/]
***** '''In patients with normal renal function and no known comorbidities there is no need to discontinue metformin before IRCM use, nor is there a need to check creatinine following the imaging study.'''
***** '''<span style="color:#ff0000">In patients with renal insufficiency metformin should be discontinued the day of the study and withheld for 48 hours. Post-procedure creatinine should be measured at 48 hours and metformin started once kidney function is normal.'''
**** It is not necessary to discontinue metformin before gadolinium-enhanced MRI studies when the amount of gadolinium administered is in the usual dosage range of 0.1 to 0.3 mmol per kilogram of body weight.
*** Prevention of CIN is of great concern and has been a subject of many different studies. Hydration is the major preventative action against CIN. Periprocedural IV hydration with 0.9% saline at 100 mL/hr 12 hours before to 12 hours after has been shown to decrease the incidence of CIN after IV contrast use
 
===== Findings =====
 
*'''<span style="color:#ff0000">Enhancement'''
** <span style="color:#ff0000">'''Hounsfield units (HU) are a standardized quantitative measurement of x-ray attenuation'''</span>[https://pubmed.ncbi.nlm.nih.gov/29362150/]
**'''If homogenous lesion and HU on non-contrast CT is[https://pubmed.ncbi.nlm.nih.gov/29362150/]'''
**'''If homogenous lesion and HU on non-contrast CT is[https://pubmed.ncbi.nlm.nih.gov/29362150/]'''
***'''<20, then simple cyst'''
***'''<span style="color:#ff0000"><20, then simple cyst'''
***'''>70, then hemorrhagic/proteinaceous cysts'''
***'''>70, then hemorrhagic/proteinaceous cysts'''
***'''20-70, then considered indeterminate and warrants further evaluation'''
***'''20-70, then considered indeterminate and warrants further evaluation'''
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***'''<10, then no enhancement'''
***'''<10, then no enhancement'''
***'''10-20, then indeterminate enhancement'''
***'''10-20, then indeterminate enhancement'''
**'''<span style="color:#ff0000">Any solid renal mass that enhances >15 Hounsfield units and does not exhibit fat density should be considered a renal cell carcinoma (RCC) until proven otherwise</span>'''
**'''<span style="color:#ff0000">Differential diagnosis of an enhancing renal mass on CT scan[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5258153/]</span>'''
*** '''Clear cell enhances more than papillary and chromophobe RCC'''
***'''<span style="color:#ff0000">Hyperdense cyst</span>'''
**** Emerging data suggests that clear cell RCC may be distinguished from the papillary subtype (papillary RCC is often hypo-enhancing). However, both malignant and benign masses can display heterogeneous avid contrast enhancement patterns and no definitive conclusion can be drawn regarding biological potential based on enhancement pattern alone
****'''Hyperdense cysts are benign lesions that contain old, degenerated, or clotted blood and have increased CT attenuation (>20 HU)'''
** '''Hyperdense cysts are benign lesions that contain old, degenerated, or clotted blood and have increased CT attenuation (>20 HU)'''
***'''<span style="color:#ff0000">Renal cell carcinoma</span>'''
** '''Solid masses that have substantial areas of negative CT attenuation (<-20 HU) indicative of fat are diagnostic of AML'''
****'''<span style="color:#ff0000">Any solid renal mass that enhances >15 Hounsfield units and does not exhibit fat density should be considered a renal cell carcinoma (RCC) until proven otherwise</span>'''
***** '''Clear cell enhances more than papillary and chromophobe RCC'''
****** Emerging data suggests that clear cell RCC may be distinguished from the papillary subtype (papillary RCC is often hypo-enhancing). However, both malignant and benign masses can display heterogeneous avid contrast enhancement patterns and no definitive conclusion can be drawn regarding biological potential based on enhancement pattern alone
** '''<span style="color:#ff0000">Solid masses that have substantial areas of negative CT attenuation (<-20 HU) indicative of fat are diagnostic of AML'''
*** '''≈5-10% of AML’s are fat poor'''
*** '''≈5-10% of AML’s are fat poor'''
*** '''In rare instances RCC may demonstrate fat''' density on imaging and even pathologically, '''but this is the exception rather than the rule'''
*** '''In rare instances RCC may demonstrate fat''' density on imaging and even pathologically, '''but this is the exception rather than the rule'''
Line 240: Line 290:
** In this setting the fat is thought to be a reactive process related to tumor necrosis.
** In this setting the fat is thought to be a reactive process related to tumor necrosis.
** Calcification is virtually never seen in association with AML.
** Calcification is virtually never seen in association with AML.
* '''Contrast-enhanced CT is the modality of choice in evaluating cystic renal masses.[https://pubmed.ncbi.nlm.nih.gov/31900669/]'''
**MRI is used when CT is contraindicated (e.g., patients with allergy to iodinated contrast agent) or as a problem-solving modality for equivocal findings. MRI can show some septa that are less apparent at CT and demonstrate definitive enhancement in those cysts that show only equivocal enhancement at CT. As a consequence, renal cysts can be placed in a higher Bosniak category with MRI than with CT'''[https://pubmed.ncbi.nlm.nih.gov/31900669/]'''
*'''Lymphadenopathy'''
*'''Lymphadenopathy'''
** '''Enlarged hilar or retroperitoneal lymph nodes (≥2 cm) on CT almost always harbor malignancy, but this should be confirmed by surgical exploration or percutaneous biopsy if the patient is not a surgical candidate.'''
** '''Enlarged hilar or retroperitoneal lymph nodes (≥2 cm) on CT almost always harbor malignancy, but this should be confirmed by surgical exploration or percutaneous biopsy if the patient is not a surgical candidate.'''
** '''Many smaller nodes prove to be inflammatory rather than neoplastic and should not preclude surgical therapy'''
** '''Many smaller nodes prove to be inflammatory rather than neoplastic and should not preclude surgical therapy'''
*
{| class="wikitable"
|+Left, endophytic, renal mass on contrast-enhanced CT scan in a 45-year old male. Radical nephrectomy pathology demonstrated pT2a, clear cell renal cell carcinoma
![[File:Kidney CT Mass Axial.png|frameless|592x592px]]
![[File:Kidney CT Mass Sagittal.png|none|thumb|655x655px]]
|-
|Axial view
|Sagittal view
|}


==== MRI ====
==== MRI ====
Line 289: Line 347:
*# '''(L)ocation relative to the polar line'''
*# '''(L)ocation relative to the polar line'''
** All components except for the (A) descriptor are scored on a 1, 2, or 3-point scale.
** All components except for the (A) descriptor are scored on a 1, 2, or 3-point scale.
* '''Range 1-12, lower number more amenable to partial nephrectomy:'''
* '''Range 4-12, lower number more amenable to partial nephrectomy:'''
** More [https://pubmed.ncbi.nlm.nih.gov/19616235/ details] on RENAL nephrometery score
** More [https://pubmed.ncbi.nlm.nih.gov/19616235/ details] on RENAL nephrometery score


=== Metastasis ===
=== Metastasis Staging ===


* '''Chest x-ray'''
* '''Chest x-ray''' in patients with suspected renal malignancy
** '''Chest is most common site of visceral metastasis'''
** Not indicated in patients with suspected or confirmed benign renal masses
** '''Indications for CT chest (3)§:'''
**'''Chest is most common site of visceral metastasis'''
**# '''Pulmonary symptoms'''
** <span style="color:#ff0000">'''Indications for CT chest (3):[https://pubmed.ncbi.nlm.nih.gov/28479239/]'''</span>
**# '''Abnormal CXR'''
**#<span style="color:#ff0000">'''Pulmonary symptoms'''</span>
**# '''High-risk disease''' (presence of thrombi, presumed adenopathy, larger tumor size, infiltrative appearance, or extensive tumor necrosis)
**#<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>
* Bone scan
* Bone scan
** Should be reserved primarily for patients with bone pain or elevated alkaline phosphatase
** Should be reserved primarily for patients with bone pain or elevated alkaline phosphatase
Line 319: Line 383:
* '''Renal mass biopsy (RMB) has a mean diagnostic rate of 86% (14% non-diagnostic rate).''' '''Histology concordance is good''' (73-98%), '''Fuhrman grade concordance is not robust''' (32-70%)
* '''Renal mass biopsy (RMB) has a mean diagnostic rate of 86% (14% non-diagnostic rate).''' '''Histology concordance is good''' (73-98%), '''Fuhrman grade concordance is not robust''' (32-70%)
** A diagnosis of malignancy or RCC on RMB is highly reliable
** A diagnosis of malignancy or RCC on RMB is highly reliable
** '''A benign biopsy must be distinguished from a non-diagnostic biopsy (renal parenchyma or connective tissues).'''
***Pooled sensitivity: 96.7%
*** '''In the case of a non-diagnostic initial biopsy, it may be expected that a diagnosis can be made with repeat biopsy''', and that the rate of malignancy remains high
***Pooled positive predictive value: 98.8%
*** Indeterminate initial biopsy should not be taken as reassurance regarding the malignant potential of the mass
***Pooled specificity: 94.4%
** A benign biopsy may not always correlate with benign histology
* '''Potential limitations of RMB include (4):'''
*** A concurrent focus of cancer may have been mised
*#'''A benign biopsy must be distinguished from a non-diagnostic biopsy (renal parenchyma or connective tissues) result.'''
** Oncocytic neoplasms may prove to be benign oncocytoma or an eosinophilic variant of one of the many subtypes of RCC (e.g. chromophone)
*#*Non-diagnostic rate of renal mass biopsy is approximately 14%, which can be substantially reduced with repeat biopsy
** '''Biopsy or aspiration of cystic renal masses is generally not advised,''' unless there is a targetable solid component, due to concerns regarding tumor spillage and a high likelihood of obtaining a non-informative result due to sampling error
*#'''A benign biopsy may not always correlate with benign histology.'''*#*Pooled negative predictive value: 80.8%
* May be performed under CT or US guidance
*#*Due to the imperfect nature of renal mass biopsy, patients with benign renal mass biopsy may warrant follow-up.
* '''Multiple core biopsies are preferred over fine needle aspiration'''
*# '''Grade concordance from biopsy to surgically resected tissue is imperfect.'''
** At least 2-3 cores being obtained with a 16-18 gauge needle to optimize diagnostic yield
*#'''Oncocytic neoplasms may represent a diagnostic dilemma.'''
* '''Risk of complications is low with the most common being (5):'''
* '''Indications'''
*# '''Renal hematoma''' (4.9%)
*# '''Clinically significant pain''' (1.2%)
*# '''Gross hematuria''' (1.0%)
*# '''Pneumothorax''' (0.6%)
*# '''Hemorrhage requiring transfusion''' (0.4%)
** '''No reported cases of tumor seeding using contemporary techniques'''§
* '''Guideline recommendations'''
** '''CUA'''
** '''CUA'''
*** '''Renal biopsy has reasonable accuracy for assessment of tumor histology and should be considered for patients in whom the results might change management'''
*** '''Renal biopsy has reasonable accuracy for assessment of tumor histology and should be considered for patients in whom the results might change management'''
** '''AUA'''
** '''AUA'''
**[https://pubmed.ncbi.nlm.nih.gov/28479239/ '''2021 AUA Guidelines on Renal Mass and Localized Renal Cancer''']
*** Currently has an adjunctive role in the diagnosis and risk stratification of patients with renal masses suspicious for RCC
*** Currently has an adjunctive role in the diagnosis and risk stratification of patients with renal masses suspicious for RCC
*** '''Should be considered when a mass is suspected to be metastatic, hematologic, inflammatory, or infectious'''
*** '''<span style="color:#ff0000">Consider biopsy when a mass is suspected to be hematologic, metastatic, inflammatory, or infectious.</span>'''
**** See Kidney Cancer: Non-Renal Cell Carcinoma Renal Malignancies Chapter Notes
**** See Kidney Cancer: Non-Renal Cell Carcinoma Renal Malignancies Chapter Notes
**** If metastatic cancer is confirmed, systemic treatment is typically prioritized.
**** If metastatic cancer is confirmed, systemic treatment is typically prioritized.
**** Index of suspicion for a non-neoplastic process, such as renal sarcoidosis, abscess, or focal pyelonephritis, should be increased in patients presenting with signs and symptoms consistent with an infectious or inflammatory condition or those with a prior history of recurrent infections or autoimmune disease
**** Index of suspicion for a non-neoplastic process, such as renal sarcoidosis, abscess, or focal pyelonephritis, should be increased in patients presenting with signs and symptoms consistent with an infectious or inflammatory condition or those with a prior history of recurrent infections or autoimmune disease
*** '''In the setting of a solid renal mass, RMB is not required for:'''
*** '''<span style="color:#ff0000">Should be obtained if it will influence management</span>'''
***# '''Young or healthy patients who are unwilling to accept the uncertainties associated with RMB'''
****'''<span style="color:#ff0000">NOT required for (2):</span>'''
***# '''Older or frail patients who will be managed conservatively independent of RMB findings'''
****#'''<span style="color:#ff0000">Young or healthy patients who are unwilling to accept the uncertainties associated with RMB</span>'''
* PET scanning coupled with administration of radioactively labeled anti–CA-IX monoclonal antibody has been reported as an alternative to RMB
****#'''<span style="color:#ff0000">Older or frail patients who will be managed conservatively independent of RMB findings</span>'''
** '''Contraindications'''
***'''<span style="color:#ff0000">Biopsy or aspiration of cystic renal masses is generally not recommended, unless there is a targetable solid component, due to (2):[https://pubmed.ncbi.nlm.nih.gov/28479239/]</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>'''
*'''Technique'''
**May be performed under CT or US guidance
** '''Multiple core biopsies are preferred over fine needle aspiration[https://pubmed.ncbi.nlm.nih.gov/28479239/]'''
*** At least 2-3 cores being obtained with a 16-18 gauge needle to optimize diagnostic yield
* '''Complications'''
**'''Risk of complications is low with the most common being (5):'''
**# '''Renal hematoma''' (4.9%)
**# '''Clinically significant pain''' (1.2%)
**# '''Gross hematuria''' (1.0%)
**# '''Pneumothorax''' (0.6%)
**# '''Hemorrhage requiring transfusion''' (0.4%)
*** '''No reported cases of tumor seeding using contemporary techniques'''§
*PET scanning coupled with administration of radioactively labeled anti–CA-IX monoclonal antibody has been reported as an alternative to RMB


=== Genetic counseling ===
=== Genetic counseling ===
Line 357: Line 431:


==== Indications ====
==== Indications ====
* '''AUA (5):'''
 
*# '''Age ≤ 46 years with renal malignancy'''
===== AUA =====
*# '''Multifocal or bilateral renal masses'''
*[https://pubmed.ncbi.nlm.nih.gov/28479239/ '''2021 AUA Guidelines on Renal Mass and Localized Renal Cancer'''] '''<span style="color:#ff0000">(5):</span>'''
*# '''Family history (first-or second-degree relative) with a history of renal malignancy'''
*#'''<span style="color:#ff0000">Age ≤ 46 years with renal malignancy</span>'''
*# '''Personal or family history suggests a familial RCC syndrome (even if kidney cancer has not been observed)'''
*#'''<span style="color:#ff0000">Multifocal or bilateral renal masses</span>'''
*# '''Pathology demonstrates histologic findings suggestive of such a familial RCC syndrome'''
*# '''<span style="color:#ff0000">Family history (first-or second-degree relative) with a history of renal malignancy</span>'''
* '''CUA (2013 CUA Guidelines on Genetic Screening for Hereditary Renal Cell Cancers)'''
*#'''<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'''
 
===== CUA =====
*'''2013 CUA Guidelines on Genetic Screening for Hereditary Renal Cell Cancers'''
*# '''Any renal tumour (benign or malignant) AND any one of the following:'''
*# '''Any renal tumour (benign or malignant) AND any one of the following:'''
*## '''Bilaterality or multifocality'''
*## '''Bilaterality or multifocality'''
Line 386: Line 465:
*## '''Tuberous sclerosis'''
*## '''Tuberous sclerosis'''


== Stage at Diagnosis ==
*United States (SEER)[https://seer.cancer.gov/statistics-network/explorer/application.html?site=71&data_type=1&graph_type=2&compareBy=sex&chk_sex_3=3&chk_sex_2=2&rate_type=2&race=1&age_range=1&stage=101&advopt_precision=1&advopt_show_ci=on&hdn_view=0&advopt_show_apc=on&advopt_display=2]
** Localized: 68%
**Regional: 14%
**Distant: 13%
**Unstaged: 5%
== Questions ==
== Questions ==


Line 426: Line 511:
## Pneumothorax
## Pneumothorax


== Next Chapter: Management of Localized and Locally Advanced Disease ==
== Next Chapter: [[Management of Localized and Locally Advanced Disease]] ==


== References ==
== References ==
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* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 57
* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 57
* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 2
* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 2
*Campbell, Steven, et al. "Renal mass and localized renal cancer: AUA guideline." ''The Journal of urology'' 198.3 (2017): 520-529.

Latest revision as of 06:34, 19 April 2024


See 2021 AUA Renal Mass and Localized RCC Guideline Notes

Includes 2013 CUA Guidelines on Genetic Screening for Hereditary Renal Cell Cancers and parts from 2014 CUA Surgical Management of Renal Cell Carcinoma Consensus Statement and 2021 AUA Renal Mass and Localized RCC Guidelines

UrologySchool.com Summary[edit | edit source]

  • Diagnosis and Evaluation in a patients with suspected renal cell carcinoma
    • History and physical exam
    • Labs:
      • AUA (5):
        1. CBC
        2. Urinalysis (including assessment of proteinuria)
        3. Serum electrolytes
        4. Liver function tests
        5. Assessment of GFR
      • CUA: CBC, Cr, AST/ALT (markers of liver dysfunction), ALP, corrected calcium (markers of bone dysfunction)
    • Imaging:
      • Primary tumour
        • AUA:
          • Multiphase CT or MRI
        • CUA:
          • Triphasic CT abdomen/pelvis
            • MRI if CT contraindicated (pregnant/allergy/CKD)
            • If thrombus present, consider doppler US/MRI to stage IVC involvement
      • Metastasis:
        • AUA:
          • CXR
            • Indications for CT chest (3):
              1. Pulmonary symptoms
              2. Abnormal CXR
              3. High-risk disease, defined by (5):
                1. Presence of thrombi
                2. Presumed adenopathy
                3. Larger tumor size
                4. Infiltrative appearance
                5. Extensive tumor necrosis
        • CUA:
          • CXR, consider CT chest if ≥stage T2
          • Bone scan, if clinically indicated or elevated alkaline phosphatase and serum calcium
          • Brain CT or MRI if large volume metastatic disease
    • Other:
      • Renal mass biopsy
      • Genetic counseling, if indicated
      • Referral to nephrology, if indicated

History and Physical Exam[edit | edit source]

History[edit | edit source]

  • Risk factors for RCC: smoking, hypertension, obesity, familial syndromes, CKD
  • Family history
  • Symptoms
    • Most (>50%) of renal masses are diagnosed incidentally during an evaluation for unrelated signs or symptoms.
      • Many remain asymptomatic and nonpalpable until they are locally advanced
        • Flank pain is usually due to hemorrhage and clot obstruction, but can also occur with locally advanced or invasive disease.
      • The “classic triad” of symptoms associated with a malignant renal mass was hematuria, flank pain and abdominal mass
        • <5% of patients in contemporary series present with these symptoms
      • Symptoms of advanced disease:
        • Flank pain
          • Locally advanced RCC usually presents with pain, generally from invasion of the posterior abdominal wall, nerve roots, or paraspinous muscles.
        • Gross hematuria
        • Constitutional symptoms such as weight loss, fever, and night sweats
      • New onset coughing or other respiratory issues may suggest pulmonary metastases
      • New neurologic symptoms may suggest cerebral metastases
  • Spontaneous perirenal hemorrhage is an uncommon presentation of RCC in which the underlying mass may be obscured. Repeat CT a few months later can provide a definitive diagnosis.

Physical Examination[edit | edit source]

  • General
    • Blood pressure
    • Performance status
    • Body habitus
    • Dermatologic lesions, which may suggest a familial RCC syndrome
  • Lymphadenopathy
    • Cervical/supraclavicular
    • Axillary
    • Groin
  • Abdomen
    • Prior abdominal scars
  • Genitals
    • Scrotum
      • Varicocele
  • Extremities
    • Lower extremity edema
  • Neurologic exam
    • Should be performed if there is any suggestion of cerebral or spinal metastases
  • Limited role in clinically localized disease
  • Physical exam findings suggestive of advanced disease (5):
    1. Palpable abdominal mass
    2. Nonreducing varicocele
    3. Right-sided varicocele
    4. Bilateral lower extremity edema resulting from venous involvement
    5. Palpable cervical lymphadenopathy

Paraneoplastic syndromes in RCC[edit | edit source]

  • Found in 10-20% of patients with metastatic RCC (NEW-HALF-CAP):
    1. Neuropathy (3%)
    2. Elevated ESR (56%, most common)
    3. Weight loss (34%)
    4. Hypertension (38%)
      • Can be due to elevated renin production by tumour, compression of renal artery, or AV fistula in tumour
    5. Anemia (36%)
    6. Elevated LFTs (14%)
      • Due to nonmetastatic hepatic dysfunction, also known as Stauffer syndrome
    7. Fever (17%)
    8. HyperCalcemia (5%)
      • Can be due to (2):
        1. Paraneoplastic phenomena (production of PTH-related protein)
        2. Osteolytic metastatic involvement of the bone
      • Signs and symptoms include nausea, anorexia, fatigue, and decreased deep tendon reflexes
      • Management includes vigorous hydration followed by diuresis with furosemide and the selective use of bisphosphonates (if adequate renal function), corticosteroids or calcitonin
    9. Amyloidosis (2%)
    10. Polycythemia (4%)
  • Management
    • Treatment of paraneoplastic syndromes has required surgical excision or systemic therapy and, except for hypercalcemia, medical therapies have not proved helpful.

Labs[edit | edit source]

  • There are no biomarkers or routine laboratory tests used to diagnose renal malignancies.

Recommended laboratory investigations in a patient with suspected RCC[edit | edit source]

AUA[edit | edit source]

  • 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer
    1. CBC
    2. Urinalysis (including assessment of proteinuria)
    3. Comprehensive metabolic panel (electrolytes, liver function tests, assessment of GFR)
    • CBC should be considered prior to any intervention
    • Urinalysis with dipstick and microscopic evaluation should be obtained to assess for proteinuria, hematuria, pyuria or signs of other genitourinary maladies.
      • Presence of proteinuria is an important prognostic indicator and can be detected by standard urine dipstick.
        • Patients with a positive dipstick test (1+ or greater) should undergo confirmation by a quantitative measurement (protein-to-creatinine ratio or albumin-to-creatinine ratio), as part of a focused medical workup for renal dysfunction.
      • Microscopic hematuria should also be further assessed to rule out a co-existing urinary tract conditions
    • The comprehensive metabolic panel should be reviewed for electrolyte abnormalities and hepatic functional parameters.
      • Abnormalities in hepatic function may prompt further workup to exclude co-existing hepatic disease or metastases which may impact management or overall prognosis
      • Elevated ALP and/or bone pain should prompt investigation of potential bone metastases
    • 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
      • Proper classification of CKD is outlined in the Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines, which takes into account (3):
        1. GFR (CKD-EPI GFR equation)
        2. Proteinuria
        3. Etiology of CKD
      • Indications for referral to nephrology in a patient with a renal mass (4):
      1. Estimated GFR < 45 mL/min/1.73m2
      2. Confirmed proteinuria
      3. Diabetics with pre-existing CKD
      4. When eGFR is expected to be <30 mL/min/1.73m2 after intervention

CUA[edit | edit source]

  • 2014 CUA Surgical Management of Renal Cell Carcinoma Consensus Statement (4):
    1. CBC
    2. Cr
    3. Markers of liver dysfunction (transaminases)
    4. Markers of bone dysfunction (ALP and corrected calcium)

Imaging[edit | edit source]

Primary[edit | edit source]

  • Radiologic classification of renal masses
    • Cystic
    • Solid
      • Differential diagnosis for radiographically detected solid renal mass:
        1. RCC
        2. Oncocytoma
        3. Angiomyolipoma
        4. Urothelial carcinoma
        5. Metastasis
        6. Abscess
        7. Infarct
        8. Vascular malformation
        9. Renal pseudotumor
        • The diagnosis of most of these lesions can be established on the basis of clinical presentation and radiographic features, occasionally combined with endourologic studies or renal mass biopsy. However, with the exception of fat-containing AML, it is often not possible to reliably distinguish RCC from benign renal neoplasms, including oncocytoma and fat-poor AML, with current diagnostic techniques.
      • Differential Diagnoses of Infiltrative Masses in the Kidney (7):
        1. Lymphoma
        2. High-grade urothelial carcinoma
        3. Sarcomatoid differentiation (chromophobe is the most prone one to have this)
        4. Collecting duct carcinoma
        5. Renal medullary carcinoma
        6. Xanthogranulomatous pyelonephritis (XGP)
        7. Metastasis (occasionally)
  • Goals of imaging are to evaluate (4):
    1. Renal mass characteristics
      • Tumor size
        • Size is inversely correlated with risk of malignancy
          • Proportion of surgically resected masses found to be benign[1]
            • <2cm: 25%
            • <4cm: 19%
      • Tumor complexity
      • Degree of contrast enhancement
      • Presence or absence of fat
      • Involvement of or juxtaposition to the renal hilum, vein, or collecting system
    2. Contralateral kidney
    3. Regional lymphadenopathy
    4. Adrenal involvement
      1. Findings suggestive of ipsilateral adrenal involvement (3):
        1. Enlarged or indistinct adrenal gland on imaging
        2. Extensive malignant replacement of the kidney
        3. Palpably abnormal adrenal gland

Modalities[edit | edit source]

Options[edit | edit source]

  1. Ultrasound
  2. CT
  3. MRI
  4. Other
    1. Contrast-enhanced US
    2. PET-CT
  • None of the current imaging modalities can reliably distinguish between benign and malignant tumors or between indolent and aggressive tumor biology

US[edit | edit source]

  • Strict US criteria for a simple cyst (3):
    1. Smooth cyst wall
    2. Round or oval shape without internal echoes
    3. Through-transmission with strong acoustic shadows posteriorly
  • Acute focal pyelonephritis (lobar nephronia) is hypoechoic
  • Angiomyolipomas are usually echogenic
  • RCCs and intrarenal abscesses have variable echogenicity
  • Angiomyolipomas demonstrate a speed-propagation artifact
    • Speed of sound in the fat is significantly slower than that in the soft tissue, due to the presence of fat in the tumor
  • A renal mass that is not clearly a simple cyst by strict US criteria should be evaluated further with CT

CT[edit | edit source]

  • Contrast-enhanced CT is the modality of choice in evaluating cystic renal masses.[2]
    • MRI is used when CT is contraindicated (e.g., patients with allergy to iodinated contrast agent) or as a problem-solving modality for equivocal findings. MRI can show some septa that are less apparent at CT and demonstrate definitive enhancement in those cysts that show only equivocal enhancement at CT. As a consequence, renal cysts can be placed in a higher Bosniak category with MRI than with CT[3]
IV contrast[edit | edit source]
  • Contraindications (2):
    1. Severe allergy
    2. Severe chronic kidney disease
    • Patients with GFR <45 ml/min/1.73m2 should receive contrast with caution
      • Patients with acute kidney injury or GFR < 30 mL/min/1.73m2 who are not undergoing renal replacement therapy should receive intravenous normal saline prophylaxis prior to receiving iodinated contrast media§.
      • Patients with GFR 30-44 mL/min/1.73m2 may be considered for intravenous fluid prophylaxis per individual physician discretion based on the patient’s risk factor for renal injury§.
        • MRI with second generation gadolinium-based intravenous contrast is now a safer option in many patients with severe CKD
    • In patients who cannot receive intravenous contrast, MRI, non-contrast CT, and US (with Doppler) can be used to characterize renal masses
  • Contrast-induced nephropathy
    • Due to intrarenal vasoconstriction and tubular necrosis
    • Risk factors
      1. Diabetes mellitus
      2. Advanced age
      3. Congestive heart failure
      4. Hypertension
      5. Dehydration
      6. Diuretic use
      7. Low hematocrit
      8. Ventricular ejection fraction < 40%
      9. Concomitant exposure to chemotherapy, aminoglycoside or nonsteroidal anti-inflammatory agents
      10. Hyperuricemia
      11. Diseases that affect renal hemodynamics, such as end-stage liver disease and nephrotic syndrome
      12. Patients with a diagnosis of a paraproteinemia syndrome/disease (e.g., multiple myeloma), history of a kidney transplant, renal tumor, renal surgery, or single kidney may also be at higher risk
      • The patients at highest risk for developing CIN are those with both diabetes and pre-existing renal insufficiency.
    • Metformin
      • Patients with type 2 diabetes mellitus receiving metformin may have an accumulation of the drug after administering intravascular radiologic contrast medium (IRCM), resulting in biguanide lactic acidosis
      • Biguanide lactic acidosis
        • Symptoms of include vomiting, diarrhea, and somnolence
        • Fatal in ≈50% of cases
        • Rare in patients with normal renal function (no defined threshold but some studies suggest <60).
          • In patients with normal renal function and no known comorbidities there is no need to discontinue metformin before IRCM use, nor is there a need to check creatinine following the imaging study.
          • In patients with renal insufficiency metformin should be discontinued the day of the study and withheld for 48 hours. Post-procedure creatinine should be measured at 48 hours and metformin started once kidney function is normal.
        • It is not necessary to discontinue metformin before gadolinium-enhanced MRI studies when the amount of gadolinium administered is in the usual dosage range of 0.1 to 0.3 mmol per kilogram of body weight.
      • Prevention of CIN is of great concern and has been a subject of many different studies. Hydration is the major preventative action against CIN. Periprocedural IV hydration with 0.9% saline at 100 mL/hr 12 hours before to 12 hours after has been shown to decrease the incidence of CIN after IV contrast use
Findings[edit | edit source]
  • Enhancement
    • Hounsfield units (HU) are a standardized quantitative measurement of x-ray attenuation[4]
    • If homogenous lesion and HU on non-contrast CT is[5]
      • <20, then simple cyst
      • >70, then hemorrhagic/proteinaceous cysts
      • 20-70, then considered indeterminate and warrants further evaluation
    • On contrast-enhanced CT, if change in HU (compared to non-contrast)[6]
      • >20, then considered enhancing
      • <10, then no enhancement
      • 10-20, then indeterminate enhancement
    • Differential diagnosis of an enhancing renal mass on CT scan[7]
      • Hyperdense cyst
        • Hyperdense cysts are benign lesions that contain old, degenerated, or clotted blood and have increased CT attenuation (>20 HU)
      • Renal cell carcinoma
        • Any solid renal mass that enhances >15 Hounsfield units and does not exhibit fat density should be considered a renal cell carcinoma (RCC) until proven otherwise
          • Clear cell enhances more than papillary and chromophobe RCC
            • Emerging data suggests that clear cell RCC may be distinguished from the papillary subtype (papillary RCC is often hypo-enhancing). However, both malignant and benign masses can display heterogeneous avid contrast enhancement patterns and no definitive conclusion can be drawn regarding biological potential based on enhancement pattern alone
    • Solid masses that have substantial areas of negative CT attenuation (<-20 HU) indicative of fat are diagnostic of AML
      • ≈5-10% of AML’s are fat poor
      • In rare instances RCC may demonstrate fat density on imaging and even pathologically, but this is the exception rather than the rule
  • Tumors with calcification associated with fat are uncommon but are almost always malignant RCC.
    • In this setting the fat is thought to be a reactive process related to tumor necrosis.
    • Calcification is virtually never seen in association with AML.
  • Lymphadenopathy
    • Enlarged hilar or retroperitoneal lymph nodes (≥2 cm) on CT almost always harbor malignancy, but this should be confirmed by surgical exploration or percutaneous biopsy if the patient is not a surgical candidate.
    • Many smaller nodes prove to be inflammatory rather than neoplastic and should not preclude surgical therapy
Left, endophytic, renal mass on contrast-enhanced CT scan in a 45-year old male. Radical nephrectomy pathology demonstrated pT2a, clear cell renal cell carcinoma
Axial view Sagittal view

MRI[edit | edit source]

  • Alternate standard to CT
    • Similar sensitivity and specificity to CT
      • Sensitivity: 88% (interquartile range [IQR] 81%-94%) CT vs. 87.5% (IQR 75.25%-100%) MRI
      • Specificity: 75% (IQR 51%-90%) CT vs. 89% (IQR 75%-96%) MRI
      • Vogel, Christina, et al. "Imaging in suspected renal-cell carcinoma: systematic review." Clinical genitourinary cancer 17.2 (2019): e345-e355.
    • Considered comparable to CT in characterizing indeterminate renal masses by the American College of Radiology[8]
    • CT may be better for smaller lesions
    • Most useful in patients in whom contrast is contraindicated because of severe allergy or severe CKD
    • Gadolinium contrast can be given to patients with GFR < 30 mL/min/1.73m2[9]
    • Nephrogenic systemic fibrosis (NSF)
      • Fibrosing dermopathy associated with soft tissue deposition and accumulation of gadolinium
      • Potentially serious complication of gadolinium contrast
      • Very rare
        • More common with group I gadolinium based contrast agents
          • Incidence <0.07% in patients with CKD 4 and 5 with group II agents
          • Group II gadolinium based contrast agents are considered safe for any level of eGFR
            • Renal function does not need be screened prior to receiving group II gadolinium based contrast agents
      • Prevention in patients with ESRD: perform hemodialysis after the MRI scan.
  • Image Sequences
    • Lesions in upper pole and lower pole may be skipped when scrolling through axial slices, always look at coronal images
    • T2WI
      • Most useful for anatomic assessment of renal masses
      • Usually two T2 sequences, one with fat suppression and one without
      • Renal vessels will be dark
    • Diffusion weighted imaging
      • Sequences with higher b-value more likely useful
  • Enhancement > 20% is suspicious for RCC
  • For a fat-containing tumor, a T2-weighted image with fat suppression is most likely to identify macroscopic fat and confirm the diagnosis of an angiomyolipoma (AML).
  • Best study for evaluation of invasion into adjacent structures
    • Large tumours may indent and compress adjacent liver parenchyma but seldom actually grow by direct extension into the liver; obliteration of the fat plane between the tumour and adjacent organs (e.g. the liver) on CT can be a misleading finding and should prompt further imaging with MRI. In reality, surgical exploration is often required to make an absolute differentiation.

Contrast-enhanced US using microbubbles[edit | edit source]

  • May play an important role in the future for characterizing renal masses in select patients in whom other forms of intravenous contrast are contraindicated.

RENAL nephrometery score[edit | edit source]

  • Based on the 5 most reproducible features that characterize the anatomy of a solid renal mass
    1. (R)adius (maximal tumor size)
    2. (E)xophytic/endophytic
    3. (N)earness of the deepest portion of the tumor to the collecting system or renal sinus
    4. (A)nterior (a)/posterior (p) descriptor
    5. (L)ocation relative to the polar line
    • All components except for the (A) descriptor are scored on a 1, 2, or 3-point scale.
  • Range 4-12, lower number more amenable to partial nephrectomy:
    • More details on RENAL nephrometery score

Metastasis Staging[edit | edit source]

  • Chest x-ray in patients with suspected renal malignancy
    • Not indicated in patients with suspected or confirmed benign renal masses
    • Chest is most common site of visceral metastasis
    • Indications for CT chest (3):[10]
      1. Pulmonary symptoms
      2. Abnormal CXR
      3. High-risk disease, defined by (5):
        1. Presence of thrombi
        2. Presumed adenopathy
        3. Larger tumor size
        4. Infiltrative appearance
        5. Extensive tumor necrosis
  • Bone scan
    • Should be reserved primarily for patients with bone pain or elevated alkaline phosphatase
  • Brain imaging for those with neurologic symptoms
  • Positron emission tomography (PET)
    • Has been investigated for patients with high risk of metastatic RCC, with most studies showing good specificity but suboptimal sensitivity.
    • Currently, PET scan has no role in the routine evaluation or staging of RCC.

Other investigations[edit | edit source]

Renal mass biopsy[edit | edit source]

  • ≈20-30% of clinically localized solid, enhancing, clinical T1 renal masses are benign
    • The smaller the tumour size, the more likely to be benign.
      • Risk of malignancy increases 30%/cm increase in tumour size
    • Young to middle-age women, in particular, are more likely to have benign pathology, as high as 40% in some series.
      • Some benign renal masses, such as cystic nephroma and atypical AML, may be influenced by the hormonal milieu and are thus more common in women
    • Most benign clinical T1 renal masses are oncocytomas or atypical AMLs.
  • Renal mass biopsy (RMB) has a mean diagnostic rate of 86% (14% non-diagnostic rate). Histology concordance is good (73-98%), Fuhrman grade concordance is not robust (32-70%)
    • A diagnosis of malignancy or RCC on RMB is highly reliable
      • Pooled sensitivity: 96.7%
      • Pooled positive predictive value: 98.8%
      • Pooled specificity: 94.4%
  • Potential limitations of RMB include (4):
    1. 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
    2. 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.
    3. Grade concordance from biopsy to surgically resected tissue is imperfect.
    4. Oncocytic neoplasms may represent a diagnostic dilemma.
  • Indications
    • CUA
      • Renal biopsy has reasonable accuracy for assessment of tumor histology and should be considered for patients in whom the results might change management
    • AUA
    • 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer
      • Currently has an adjunctive role in the diagnosis and risk stratification of patients with renal masses suspicious for RCC
      • Consider biopsy when a mass is suspected to be hematologic, metastatic, inflammatory, or infectious.
        • See Kidney Cancer: Non-Renal Cell Carcinoma Renal Malignancies Chapter Notes
        • If metastatic cancer is confirmed, systemic treatment is typically prioritized.
        • Index of suspicion for a non-neoplastic process, such as renal sarcoidosis, abscess, or focal pyelonephritis, should be increased in patients presenting with signs and symptoms consistent with an infectious or inflammatory condition or those with a prior history of recurrent infections or autoimmune disease
      • Should be obtained if it will influence management
        • NOT required for (2):
          1. Young or healthy patients who are unwilling to accept the uncertainties associated with RMB
          2. Older or frail patients who will be managed conservatively independent of RMB findings
    • Contraindications
      • Biopsy or aspiration of cystic renal masses is generally not recommended, unless there is a targetable solid component, due to (2):[11]***#Concerns regarding tumor spillage
        1. High likelihood of obtaining a non-informative result due to sampling error
  • Technique
    • May be performed under CT or US guidance
    • Multiple core biopsies are preferred over fine needle aspiration[12]
      • At least 2-3 cores being obtained with a 16-18 gauge needle to optimize diagnostic yield
  • Complications
    • Risk of complications is low with the most common being (5):
      1. Renal hematoma (4.9%)
      2. Clinically significant pain (1.2%)
      3. Gross hematuria (1.0%)
      4. Pneumothorax (0.6%)
      5. Hemorrhage requiring transfusion (0.4%)
      • No reported cases of tumor seeding using contemporary techniques§
  • PET scanning coupled with administration of radioactively labeled anti–CA-IX monoclonal antibody has been reported as an alternative to RMB

Genetic counseling[edit | edit source]

  • Benefits (2):
    1. May allow for more intensive evaluation of the patient for RCC and associated manifestations
    2. Identification of blood relatives that may be at syndromic risk

Indications[edit | edit source]

AUA[edit | edit source]
  • 2021 AUA Guidelines on Renal Mass and Localized Renal Cancer (5):
    1. Age ≤ 46 years with renal malignancy
    2. Multifocal or bilateral renal masses
    3. Family history (first-or second-degree relative) with a history of renal malignancy
    4. Personal or family history suggests a familial RCC syndrome (even if kidney cancer has not been observed)
    5. Pathology demonstrates histologic findings suggestive of such a familial RCC syndrome
      • Hybrid oncocytic/chromophobe tumors are suggestive of BHD
CUA[edit | edit source]
  • 2013 CUA Guidelines on Genetic Screening for Hereditary Renal Cell Cancers
    1. Any renal tumour (benign or malignant) AND any one of the following:
      1. Bilaterality or multifocality
      2. Age of onset ≤45
      3. 1st or 2nd degree relative with any renal tumour
      4. Stigmata of RCC syndrome (8)
        1. History of pneumothorax* (*or 1st degree relative with same) (found in BHDS)
        2. Pulmonary lymphangiomyomatosis* (TSC)
        3. Childhood seizure disorder* (TSC)
        4. Skin leiomyomas* (HLRCC)
        5. Skin fibrofolliculomas/ trichodisomas* (BHDS)
        6. Pheochromocytoma/ paraganglioma* (VHL)
        7. Hemangioblastoma of the retina, brainstem, cerebellum or spinal cord* (VHL)
        8. Early onset of multiple uterine fibroids (<30 years of age)* (HLRCC)
    2. Non-ccRCC with unusual associated features (e.g., chromophobe, oncocytic or hybrid tumours)
    3. Patients, with or without RCC, who report a family member (any) with any one of the following:
      1. Von Hippel-Lindau syndrome
      2. Hereditary papillary renal cell cancer
      3. Hereditary leiomyomatosis and renal cell cancer
      4. Birt-Hogg-Dubé syndrome
      5. Hereditary paraganglioma/ pheochromocytoma
      6. Tuberous sclerosis

Stage at Diagnosis[edit | edit source]

  • United States (SEER)[13]
    • Localized: 68%
    • Regional: 14%
    • Distant: 13%
    • Unstaged: 5%

Questions[edit | edit source]

  1. What is the differential diagnosis for a solid mass on imaging?
  2. What are the recommended investigations in patients with suspected RCC?
  3. What are the paraneoplastic syndromes associated with RCC?
  4. What findings are suggestive of ipsilateral adrenal involvement
  5. What are potential complications related to renal mass biopsy?

Answers[edit | edit source]

  1. What is the differential diagnosis for a solid mass on imaging?
    • Malignant: RCC, urothelial carcinoma, sarcoma, lymphoma, metastasis
    • Benign: oncocytoma, abscess, infarct, vascular malformation, renal pseudotumour
  2. What are the recommended investigations in patients with suspected RCC?
    • History and physical
    • Laboratory investigations: CBC, Cr, LFTs, calcium
    • Imaging: Triphasic CT abdo/pelvis, CXR or CT chest
  3. What are the paraneoplastic syndromes associated with RCC?
    1. Neuropathy
    2. Elevated ESR
    3. Weight loss
    4. Hypertension
    5. Anemia
    6. LFTs elevated
    7. Fever
    8. Hypercalcemia
    9. Amyloidosis
    10. Polychythemia
  4. What findings are suggestive of ipsilateral adrenal involvement
    1. Enlarged or indistinct adrenal gland on imaging
    2. Extensive malignant replacement of kidney
    3. Palpably abnormal adrenal gland
  5. What are potential complications related to renal mass biopsy?
    1. Bleeding
      1. Renal hematoma
      2. Gross hematuria
      3. Hemorrhage requiring transfusions
    2. Pain
    3. Pneumothorax

Next Chapter: Management of Localized and Locally Advanced Disease[edit | edit source]

References[edit | edit source]

  • Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 57
  • Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 2
  • Campbell, Steven, et al. "Renal mass and localized renal cancer: AUA guideline." The Journal of urology 198.3 (2017): 520-529.