What are the treatment options for a patient diagnosed with Renal Cell Carcinoma (RCC)?

Treatment Options for Renal Cell Carcinoma

The treatment of RCC is determined by disease stage: for localized disease (T1 tumors <7 cm), partial nephrectomy is the recommended first-line treatment; for metastatic disease, combination immunotherapy with nivolumab plus ipilimumab is recommended for intermediate- and poor-risk patients, while VEGF-targeted agents or immunotherapy/TKI combinations are options for good-risk patients. 1

Localized/Locoregional Disease Management

T1 Tumors (<7 cm)

• Partial nephrectomy (PN) is the preferred surgical approach for organ-confined T1 tumors, preserving renal function while achieving equivalent oncologic outcomes to radical nephrectomy 1
• Laparoscopic radical nephrectomy is recommended if partial nephrectomy is not technically feasible 1
• For patients with compromised renal function, solitary kidney, or bilateral tumors, partial nephrectomy is recommended regardless of tumor size 1

Alternative Approaches for Small Tumors

• Ablative therapies (radiofrequency ablation, microwave ablation, or cryoablation) are options for small cortical tumors ≤3 cm in frail patients, those with high surgical risk, solitary kidney, compromised renal function, or hereditary RCC 1
• Renal biopsy is recommended before ablative treatments to confirm malignancy and histologic subtype 1
• Active surveillance is appropriate for elderly patients (≥75 years) with significant comorbidities or short life expectancy and solid renal tumors <40 mm, with biopsy recommended for patient selection 1

T2-T4 Tumors (Larger and Locally Advanced)

• For T2 tumors >7 cm, laparoscopic radical nephrectomy is the preferred option 1
• For T3 and T4 tumors (locally advanced), open radical nephrectomy remains the standard of care, although laparoscopic approach can be considered in select cases 1
• Routine adrenalectomy and extensive lymph node dissection are not recommended unless imaging shows evidence of involvement 1

Advanced/Metastatic Disease Management

Surgical Considerations

• Cytoreductive nephrectomy is recommended in patients with good performance status and large primary tumors, except in intermediate- and poor-risk patients with asymptomatic primary tumors when immediate medical treatment is required 1
• Metastasectomy should be considered for select patients with solitary or easily accessible metastases, particularly with long disease-free intervals 1, 2

First-Line Systemic Treatment

For Intermediate- and Poor-Risk Patients:

• Nivolumab plus ipilimumab combination is the recommended first-line treatment (Level I, A evidence; ESMO-MCBS score: 3) 1, 3
• Cabozantinib monotherapy is approved for intermediate-risk (ESMO-MCBS score: 3) and poor-risk groups (ESMO-MCBS score: 3) 1

For Good- and Intermediate-Risk Patients:

• VEGF-targeted agents and tyrosine kinase inhibitors (TKIs) are recommended options 1
• Sunitinib 50 mg orally once daily on a 4-weeks-on/2-weeks-off schedule is FDA-approved for advanced RCC 4
• Tivozanib is EMA-approved specifically for good-risk patients 1
• Immunotherapy/TKI combinations (pembrolizumab, nivolumab, or avelumab with axitinib, lenvatinib, or cabozantinib) are approved regardless of prognostic group 5

Second-Line Systemic Treatment

• Following TKI failure, nivolumab (Level I, A; ESMO-MCBS score: 5) or cabozantinib (Level I, A; ESMO-MCBS score: 3) is recommended 1, 3
• Lenvatinib plus everolimus combination is FDA- and EMA-approved following TKIs (ESMO-MCBS score: 4) and after nivolumab/ipilimumab combination 1
• In patients already treated with two TKIs, either nivolumab or cabozantinib is recommended 1
• If these drugs are unavailable, everolimus or axitinib can be used 1

Radiation Therapy for Metastatic Disease

• Radiotherapy is effective for palliation of symptomatic metastatic disease or prevention of progression in critical sites such as bone or brain (Level I, A) 1
• Image-guided techniques such as VMAT or SBRT are needed to deliver high doses 1
• For brain metastases, corticosteroids provide temporary symptom relief; WBRT 20-30 Gy in 4-10 fractions is recommended for symptom control 1
• For good-prognosis patients with single unresectable brain metastasis, stereotactic radiosurgery (SRS) with or without WBRT should be considered 1, 2

Adjuvant Treatment

• Sunitinib 50 mg orally once daily on a 4-weeks-on/2-weeks-off schedule for nine 6-week cycles is FDA-approved for adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy 4
• There is no other recommended adjuvant treatment outside clinical trials for localized disease 1

Important Caveats and Pitfalls

Patient Selection

• Nivolumab/ipilimumab is NOT recommended for good-risk patients in the first-line setting 1
• Performance status is critical: cytoreductive nephrectomy should not be performed in patients with poor performance status 1
• High-dose IL-2 should be discussed with appropriate mRCC patients who have undergone nephrectomy and have good performance status, though its role remains limited 1

Diagnostic Considerations

• Renal biopsy is mandatory before starting systemic treatment in metastatic disease without prior histological confirmation 1, 2
• Most clinical trial data applies to clear cell histology; treatment efficacy in non-clear cell subtypes is less established 1, 5

Monitoring

• Sunitinib requires hepatic function monitoring due to risk of severe or fatal hepatotoxicity 4
• For high-risk patients post-surgery, CT scans of thorax and abdomen every 3-6 months for the first 2 years are recommended 1
• For metastatic RCC patients during systemic therapy, 2-4 month follow-up with CT scan is advised 1