What are the treatment options for renal cancer?

Treatment Options for Renal Cancer

For localized renal cell carcinoma (RCC), partial nephrectomy is the preferred surgical approach for all T1 tumors (≤7 cm), while radical nephrectomy remains standard for larger or locally advanced disease, and systemic therapy with targeted agents or immunotherapy combinations is indicated for metastatic disease. 1

Localized Disease (T1-T2)

Small Renal Masses (T1a: ≤4 cm)

• Partial nephrectomy is the treatment of choice if negative surgical margins can be obtained with acceptable morbidity risk 1
• Laparoscopic or robotic approaches are acceptable alternatives to open surgery, with equivalent cancer-free survival rates 1
• Ablative therapies (radiofrequency ablation or cryoablation) are appropriate options for patients >70 years old, those with high surgical risk, solitary kidney, compromised renal function, hereditary RCC, or multiple bilateral tumors 1
• Active surveillance is a reasonable option for patients ≥75 years with significant comorbidities and solid renal tumors <4 cm 1

Larger Localized Tumors (T1b-T2: 4-7 cm and >7 cm)

• Partial nephrectomy remains preferred for T1b tumors (4-7 cm) when technically feasible, as it preserves renal function without compromising oncologic outcomes 1
• Laparoscopic radical nephrectomy is the preferred option for organ-confined RCC when partial nephrectomy is not feasible 1
• Radical nephrectomy should not be used when nephron-sparing surgery can be achieved, as radical nephrectomy increases risks of chronic kidney disease, cardiovascular morbidity, and mortality 1

Key Surgical Principles

• Routine adrenalectomy is NOT recommended unless CT imaging shows abnormal-appearing adrenal glands or the tumor involves the upper pole 1
• Routine lymph node dissection is NOT required for all radical nephrectomies unless there are palpable or CT-detected enlarged lymph nodes 1
• Lymph node dissection provides prognostic information but is not therapeutic, as virtually all patients with nodal involvement relapse with distant metastases 1

Locally Advanced Disease (T3-T4)

Surgical Management

• Open radical nephrectomy remains the standard of care for locally advanced RCC, though laparoscopic approach can be considered in select cases 1, 2
• The surgical goal is to obtain negative margins 1, 2
• For tumors with venous thrombus (common in T3 disease), surgical resection of the thrombus should be considered, though the approach depends on thrombus level and is associated with high complication risk 1, 2

Adjuvant Therapy

• Currently, there is no universally recommended adjuvant treatment following surgery for locally advanced disease 1, 2
• The S-TRAC trial showed improved disease-free survival with adjuvant sunitinib but no overall survival benefit 1
• The European Medicines Agency has not approved adjuvant VEGFR-targeted therapy due to imbalanced risk-benefit profile 2
• Enrollment in clinical trials should be encouraged for patients with high-risk disease 1, 2
• Neoadjuvant approaches are experimental and should NOT be used outside clinical trials 1, 2

Metastatic Disease

Role of Cytoreductive Nephrectomy

• Cytoreductive nephrectomy is recommended for patients with good performance status, large primary tumors, and limited volumes of metastatic disease 1, 2
• Cytoreductive nephrectomy is also indicated for symptomatic primary lesions 1
• Cytoreductive nephrectomy is NOT recommended in patients with poor performance status 1

Metastasectomy and Local Therapies

• Complete metastasectomy should be considered for selected patients with solitary or oligometastatic disease, metachronous disease with disease-free interval >2 years, good performance status, and absence of progression on systemic therapy 1
• Local treatment strategies including stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and conventional radiotherapy can be considered after multidisciplinary review 1
• No systemic treatment is recommended after complete metastasectomy 1

First-Line Systemic Therapy

For Clear Cell RCC with Good/Intermediate Prognosis:

• Nivolumab plus ipilimumab is a first-line option for intermediate or poor risk advanced RCC 3
• Nivolumab plus cabozantinib is a first-line option for advanced RCC 3
• Sunitinib (50 mg orally once daily for 4 weeks of each 6-week cycle) is approved for advanced RCC 4
• Pazopanib has demonstrated non-inferiority to sunitinib 1
• Bevacizumab combined with interferon-alpha is an option 1
• All three VEGF-targeted options (sunitinib, pazopanib, bevacizumab+IFN) have level I, A evidence 1

For Poor Prognosis Patients:

• Nivolumab plus ipilimumab is indicated for intermediate or poor risk advanced RCC 3
• Temsirolimus has level II, A evidence as the only drug with level I evidence specifically in poor prognosis patients 1

Second-Line Systemic Therapy

• After cytokine therapy: Sorafenib, pazopanib, or axitinib are active options 1
• After first-line VEGF-targeted therapy: Both axitinib and everolimus are active, with significantly improved progression-free survival 1

Third-Line and Beyond

• In patients treated with two TKIs: Everolimus is recommended 1
• In patients previously treated with VEGF-targeted therapy and mTOR inhibitor: Sorafenib has shown activity 1
• Enrollment in clinical trials is recommended when possible 1

Important Caveats and Pitfalls

Surgical Considerations

• Avoid radical nephrectomy when partial nephrectomy is feasible, as radical nephrectomy increases risk of chronic kidney disease and cardiovascular events 1
• Partial nephrectomy provides equivalent cancer-specific survival to radical nephrectomy for T1 tumors with better preservation of renal function 5, 6
• Cancer-specific survival after partial nephrectomy is 88.2% at 5 years and 73% at 10 years 5

Systemic Therapy Monitoring

• Sunitinib requires hepatotoxicity monitoring: Monitor liver function tests at baseline, during each cycle, and as clinically indicated; interrupt for Grade 3 hepatotoxicity and discontinue for Grade 4 4
• Monitor for cardiovascular events including myocardial ischemia, heart failure, and decreased left ventricular ejection fraction with sunitinib 4
• Monitor blood pressure as hypertension is common with VEGF-targeted agents; interrupt for Grade 3 hypertension 4

Risk Stratification

• T3 clear cell RCC is high risk with 5-year metastasis-free survival of approximately 31.2% for patients with SSIGN score ≥6 1, 2
• Risk factors include nuclear grade 3-4, tumor size ≥10 cm, and histological tumor necrosis 1, 2