Renal Mass and Localized Renal Cancer (2021)

See 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

• History and physical
• Imaging:
  • Regional: multiphase, cross-sectional abdominal imaging
    • 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
  • Distant: chest x-ray in patients with suspected renal malignancy
    • Not indicated in patients with suspected or confirmed benign renal masses
    • 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
• Labs (3):
  1. CBC
  2. Urinalysis (including assessment of proteinuria)
  3. Comprehensive metabolic panel (electrolytes, liver function tests, assessment of GFR)

     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

• Other
  • Referral for genetic counseling, if indicated
    • Indications for genetic counseling (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
  • Referral to nephrology, if indicated
    • Indications for referral to nephrology in a patient with a renal mass undergoing intervention (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

Optional

• Renal mass biopsy
  • 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):
    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
    • Consider biopsy when a mass is suspected to be hematologic, metastatic, inflammatory, or infectious.
    • 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
    • Biopsy or aspiration of cystic renal masses is generally not recommended, due to (2):
      1. Concerns regarding tumor spillage
      2. High likelihood of obtaining a non-informative result due to sampling error
  • 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

1. Nephrectomy (partial vs. radical)
2. Thermal ablation (radiofrequency vs. cryoablation)
3. Active surveillance

Nephrectomy

• Partial nephrectomy
  • Indications (when intervention is necessary for solid or Bosniak 3/4 complex cystic renal mass)
    • Absolute (3):
      1. Anatomic or functionally solitary kidney
      2. Bilateral tumors
      3. Known familial RCC syndrome
    • Relative (6):
      1. cT1a renal masses (preferred over TA and RN), not managed with active surveillance
      2. Pre-existing CKD
      3. Pre-existing proteinuria
      4. Young age
      5. Multifocal masses
      6. Comorbidities that are likely to impact future renal function, including (4):
         1. Moderate to severe hypertension
         2. Diabetes mellitus
         3. Recurrent urolithiasis
         4. Morbid obesity
  • Surgical considerations
    • Renal function can be optimized by (2):
      1. Optimizing nephron mass preservation
      2. 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:
          1. Familial RCC syndromes
             • Aggressive RCC syndromes, such as HLRCC, should be best managed with wide margin PN or RN.
          2. Multifocal disease
          3. Severe CKD
• Radical nephrectomy
  • Indication (1) (when intervention is necessary for solid or Bosniak 3/4 complex cystic renal mass):
    1. If ALL criteria are met (3):
       1. High tumor complexity and PN would be challenging even in experienced hands
       2. No pre-existing CKD or proteinuria
       3. Normal contralateral kidney and new baseline eGFR will likely be > 45 mL/min/1.73m2 even if RN is performed
       • If ALL are not met, PN should be considered unless there are overriding concerns about the safety or oncologic efficacy of PN.
• Lymphadenectomy
  • Indications (1):
    1. Clinically concerning regional lymphadenopathy (for staging purposes)
• Adrenalectomy
  • Indications
    • Absolute (1):
      1. If preoperative imaging or intraoperative inspection suggests metastasis or adrenal enlargement
         • One exception is when patient has a well-characterized adenoma, which may not mandate surgical excision
    • Relative (1):
      1. Locally advanced features are identified preoperatively or during exploration and the gland is in close proximity to the tumour
         • Adrenal may be spared in this setting if the contralateral adrenal gland is absent and the ipsilateral gland demonstrates normal morphology and no malignant involvement.
• 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):
    1. Metastasis
    2. Incompletely resected disease

Thermal ablation (TA)

• Indications
  • Alternative approach for management of cT1a solid renal masses <3cm
  • 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)

• Indications
  • Absolute (1):
    1. Risk of intervention/competing risks of death outweighs the potential benefits of intervention
  • Relative (9):
    • Tumour factors (2)
      1. Solid renal mass < 2cm
         • In patients with familial RCC syndromes, tumours can be observed if <3 cm as the risk of metastases remains low in this setting
           • HLRCC and succinate dehydrogenase deficiency RCC are the exception as tumors in these syndromes are often very aggressive.
      2. Complex but predominantly cystic renal masses
    • Patient factors (7)
      1. Elderly
      2. Life expectancy < 5 years
      3. High calculated comorbidities
      4. Excessive perioperative risk
      5. Poor functional status
      6. Marginal renal function (≥CKD3b)
      7. 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.
• In patients undergoing AS, periodic clinical surveillance and/or imaging is recommended in asymptomatic patients
  • 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.
• Indications for "intervention" (treatment or increased AS intensity) (5):§:
  1. Tumour size >3cm
  2. Growth kinetics (>5mm/year)
     • Caution if different imaging modalities are used due to normal variations in maximal tumor diameter and volume calculations; interreader variability may also be significant.
  3. Stage progression
  4. Clinical changes in patient/tumour factors (e.g. infiltrative on imaging, suspicion of advanced T stage)
  5. Additional biopsy results (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):
  1. Serum creatinine, eGFR
  2. 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):
        1. Bone pain
        2. Elevated alkaline phosphatase
        3. 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):
        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

• Risk-stratified into (4):
  1. Low-risk: pT1 and Grade 1/2
  2. Intermediate-risk: pT1 and Grade 3/4, or pT2 any Grade
  3. High-risk: pT3 any Grade
  4. 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.
• Follow-up based on risk stratification
  • See Table 1 from original guidelines
    • If low-risk, abdominal and chest imaging at 12, 24, 48 and 60 months
    • 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 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.