What is the management approach for renal cell carcinoma?

Management Approach for Renal Cell Carcinoma

The management of renal cell carcinoma requires a stage-specific approach, with surgical intervention being the cornerstone for localized disease and systemic therapy with targeted agents or immunotherapy for advanced or metastatic disease. 1

Diagnosis and Staging

• Laboratory examinations including serum creatinine, hemoglobin, leukocyte and platelet counts, lymphocyte to neutrophil ratio, lactate dehydrogenase, CRP, and serum-corrected calcium tests should be performed to confirm suspicion of RCC 1
• Contrast-enhanced chest, abdominal, and pelvic CT are recommended for accurate staging 1
• Renal tumor core biopsy is recommended before ablative therapies and in patients with metastatic disease before starting systemic treatment 1
• The UICC TNM 8 staging system should be used for proper classification 1

Management of Localized Disease

T1 Tumors (<7 cm)

• Partial nephrectomy (PN) is recommended as the first-line approach to preserve renal function 1, 2
• Laparoscopic radical nephrectomy (RN) is recommended if PN is not feasible 1
• For patients with compromised renal function or bilateral tumors, PN is recommended regardless of tumor size 1

Small Renal Masses

• Radiofrequency ablation (RFA), microwave ablation (MWA), or cryoablation (CA) are options for:
  • Small cortical tumors ≤3 cm
  • Frail patients
  • High surgical risk
  • Solitary kidney
  • Compromised renal function
  • Hereditary RCC or bilateral tumors 1, 2
• Active surveillance can be considered for elderly patients with significant comorbidities and solid renal tumors <40 mm 1

T2 Tumors (>7 cm)

• Laparoscopic radical nephrectomy is the preferred option 1

T3 and T4 Tumors (Locally Advanced)

• Open radical nephrectomy is the standard of care, although laparoscopic approach can be considered in select cases 1

Management of Advanced/Metastatic Disease

Cytoreductive Nephrectomy

• Cytoreductive nephrectomy (CN) is recommended in patients with good performance status 1
• CN should be avoided in intermediate and poor-risk patients with asymptomatic primary tumors when systemic treatment is required 1

First-Line Systemic Therapy

• For good and intermediate-risk patients:

  • VEGF-targeted agents and tyrosine kinase inhibitors (TKIs) are recommended options 1
  • Immune checkpoint inhibitor (ICI) in combination with a VEGFR TKI is recommended 2
  • Tivozanib is approved for good-risk patients 1

• For intermediate or poor-risk disease:

  • Combination treatment with either two immune checkpoint inhibitors or an ICI with a VEGFR TKI is recommended 2
  • Ipilimumab plus nivolumab is a preferred option 1, 2

Second-Line Systemic Therapy

• After VEGFR TKI monotherapy: nivolumab or cabozantinib 1
• After combination immunotherapy: VEGFR TKI monotherapy 1
• After VEGFR TKI with an immune checkpoint inhibitor: an alternative VEGFR TKI as a single agent 1

Management of Metastatic Sites

Low-Volume Metastatic Disease

• Definitive metastasis-directed therapies including surgical resection (metastasectomy), ablative measures, or radiotherapy may be offered 1

Bone Metastases

• Bone-directed radiation for symptomatic lesions 1
• Bone resorption inhibitor (bisphosphonate or RANKL inhibitor) when there is clinical concern for fracture or skeletal-related events 1
• Cabozantinib-containing regimens may be preferred for systemic treatment 1

Brain Metastases

• Brain-directed local therapy with radiation therapy and/or surgery 1
• For symptomatic relief, corticosteroids can provide temporary relief 1
• Whole brain radiation therapy (WBRT) between 20-30 Gy in 4-10 fractions for symptom control 1
• For single unresectable brain metastasis in good-prognosis patients, stereotactic radiosurgery (SRS) with or without WBRT should be considered 1
• Immune checkpoint inhibitor-based combination therapy is preferred for first-line systemic treatment 1

Sarcomatoid Features

• Immune checkpoint inhibitor-based combination first-line treatment (ipilimumab plus nivolumab, or alternatively, an immune checkpoint inhibitor plus a TKI) 1

Special Considerations

• For patients on immunotherapy who experience limited disease progression (e.g., one site of progression), local therapy (radiation, thermal ablation, excision) may be offered, and immunotherapy may be continued 1
• Risk stratification using validated prognostic models such as MSKCC or IMDC criteria should guide treatment decisions 2
• Enrollment in clinical trials should be considered, especially for patients with non-clear cell histology 2

Common Pitfalls to Avoid

• Failing to risk-stratify patients with metastatic disease before selecting therapy 2
• Using high-dose IL-2 outside of experienced high-volume centers 2
• Neglecting the role of local therapies in oligometastatic disease 1
• Overlooking the potential benefit of continuing immunotherapy after limited progression when local therapy can be applied 1