What are the treatment options for renal cancer based on the stage of the disease?

Treatment Options for Renal Cancer Based on Stage

The treatment of renal cell carcinoma should be guided primarily by tumor stage, with surgical options for localized disease and systemic therapy for advanced disease, prioritizing approaches that maximize survival and quality of life. 1

Stage I Disease

• For stage IA renal masses (≤4 cm), partial nephrectomy is the preferred surgical approach to preserve renal function while maintaining equivalent oncological outcomes to radical nephrectomy 2
• Partial nephrectomy is particularly important for patients with small unilateral tumors, uninephric patients, those with renal insufficiency, bilateral renal masses, or familial RCC 2
• Both open and laparoscopic approaches to partial nephrectomy can be considered, depending on tumor size, location, and surgeon expertise 2
• Alternative options for selected patients with stage IA RCC include active surveillance (particularly for elderly patients or those with significant comorbidities) and thermal ablation techniques 2
• For stage IB tumors (4-7 cm), either radical or partial nephrectomy (whenever feasible) is the standard of care 2, 1
• The 5-year survival rate for stage I renal cell carcinoma is approximately 95% 1, 3

Stage II and III Disease

• Radical nephrectomy is the standard of care for patients with stage II and III renal tumors 2
• For T3 tumors (extending into major veins or perinephric tissues), radical nephrectomy is the preferred treatment, especially if the tumor extends into the inferior vena cava 2, 4
• Resection of a caval or atrial thrombus often requires the assistance of cardiovascular surgeons and may involve veno-venous or cardiopulmonary bypass techniques 2
• Surgery for caval or atrial tumor thrombus should be performed by experienced teams, as treatment-related mortality may reach 10% 2
• Systematic adrenalectomy is not recommended when abdominal CT shows no evidence of adrenal invasion 4
• Extensive lymph node dissection is not routinely recommended unless there is clinical evidence of lymph node involvement 4
• The 5-year survival rate for stage II is approximately 88% and for stage III approximately 59% 1

Stage IV (Advanced/Metastatic) Disease

• For patients with stage IV disease who have poor-risk features, clear cell histology, and high-volume distant metastases, systemic therapy is the preferred initial treatment option rather than cytoreductive nephrectomy 2
• This recommendation is based on the CARMENA trial, which showed sunitinib alone was noninferior to sunitinib after nephrectomy in intermediate and poor-risk patients 2
• Cytoreductive nephrectomy may still be considered in patients with excellent performance status and small-volume distant metastases 2
• For intermediate or poor-risk advanced clear cell RCC, nivolumab plus ipilimumab is recommended as first-line therapy 1, 5
• For good and intermediate-risk patients, VEGF-targeted agents and tyrosine kinase inhibitors (TKIs) are recommended as first-line therapy options 1, 6
• The 5-year survival rate for stage IV renal cell carcinoma is approximately 12-20% 2, 1

Post-Surgical Management

• After surgical excision, 20-30% of patients with localized tumors experience relapse, with lung being the most common site of distant recurrence (50-60% of patients) 2
• The median time to relapse after surgery is 1-2 years, with most relapses occurring within 3 years 2
• Adjuvant treatment after nephrectomy currently has no established role in patients who have undergone a complete resection of their tumor 2, 4
• Observation remains standard care after nephrectomy, and eligible patients should be offered enrollment in randomized clinical trials 2
• Follow-up for patients with completely resected disease includes abdominal and chest CT scans obtained approximately 4-6 months after surgery and then as clinically indicated 2

Important Considerations and Pitfalls

• Histologic diagnosis of RCC is crucial for therapy selection, with clear cell RCC being the most common subtype (70-80% of cases) 2, 3
• Risk stratification using models like the MSKCC or IMDC criteria is essential for guiding treatment selection, particularly for advanced disease 2
• Attempting to downsize venous tumor thrombi with systemic targeted therapy before surgery is not recommended 4
• Neoadjuvant approaches are still experimental and should not be proposed outside of clinical trials 4
• The improved prognosis in renal cancer depends on earlier detection and refinement of therapeutic methods 7, 3