What are the treatment options for kidney cancer?

Treatment Options for Kidney Cancer

For localized kidney cancer (Stage I-III), nephron-sparing partial nephrectomy is the preferred treatment for tumors ≤7 cm, while radical nephrectomy is indicated for larger tumors; for metastatic disease, first-line systemic therapy with immune checkpoint inhibitor combinations (nivolumab/ipilimumab or pembrolizumab/axitinib) is preferred for intermediate/poor-risk patients, while cytoreductive nephrectomy should be avoided in this population. 1

Localized Disease (Stage I-III)

Stage I Tumors (≤7 cm)

• Partial nephrectomy is the first-line treatment for T1 tumors (<7 cm), preserving renal function with equivalent oncologic outcomes to radical nephrectomy and achieving 5-year survival rates of approximately 95% 1, 2
• Open, laparoscopic, or robotic surgical approaches provide comparable outcomes in experienced hands 1, 3
• Warm ischemia time should ideally be kept under 30 minutes to preserve renal function 1, 3

Alternative Options for Small Tumors

• Ablative techniques (cryoablation, radiofrequency ablation) can be considered for selected patients with clinical stage T1 lesions, particularly those with high surgical risk, though these carry higher local recurrence rates than conventional surgery 1
• Active surveillance is appropriate for elderly patients with significant comorbidities or solid renal tumors <40 mm, with renal biopsy recommended to confirm malignancy 1, 4

Stage II-III Tumors (>7 cm or Locally Advanced)

• Radical nephrectomy is the preferred option for T2 tumors (>7 cm), achieving 5-year survival rates of approximately 88% 1, 2
• For T3-T4 tumors, radical nephrectomy plus adrenalectomy (if involved) is recommended, with 5-year survival rates of approximately 59% 2
• Regional lymph node dissection is recommended for patients with adenopathy on preoperative imaging or palpable adenopathy at surgery 1

Metastatic Disease (Stage IV)

Initial Management Strategy

Systemic therapy is now the preferred initial treatment for patients with intermediate- or poor-risk features and high-volume metastases, rather than upfront cytoreductive nephrectomy 1, 4

This recommendation is based on the CARMENA trial showing superior outcomes with sunitinib alone versus nephrectomy followed by sunitinib in this population (median OS 18.4 vs 13.9 months) 1

Cytoreductive Nephrectomy - Limited Role

Cytoreductive nephrectomy may still be considered for highly selected patients who have:

• Excellent performance status (ECOG PS <2) 1
• Small-volume distant metastases 1
• No brain metastases 1
• Good-risk features 1, 4

First-Line Systemic Therapy for Clear Cell RCC

Preferred Regimens (All Risk Groups):

• Axitinib plus pembrolizumab (Category 1, preferred) - FDA-approved based on KEYNOTE-426 trial showing superior ORR and PFS compared to sunitinib 1
• Nivolumab plus ipilimumab - particularly preferred for intermediate- and poor-risk patients, achieving tumor response rates of 42-71% with median OS of 46-56 months 1, 5
• Nivolumab plus cabozantinib - FDA-approved for first-line treatment of advanced RCC 5

Other Recommended Regimens:

• Pazopanib (Category 1) 1
• Sunitinib (Category 1) - 50 mg orally once daily for 4 weeks of each 6-week cycle 1, 6
• Bevacizumab plus interferon-α (Category 1) 1

Risk Stratification Guides Treatment Selection

Use IMDC criteria (more relevant than MSKCC in modern practice) to stratify patients: 1

• Favorable risk: 0 prognostic factors
• Intermediate risk: 1-2 prognostic factors
• Poor risk: ≥3 prognostic factors

IMDC factors include: interval from diagnosis to treatment <1 year, Karnofsky performance status <80%, hemoglobin below lower limit of normal, corrected calcium above upper limit of normal, neutrophil count above upper limit of normal, platelet count above upper limit of normal 1

Non-Clear Cell Histology

Preferred options include: 1

• Everolimus
• Lenvatinib plus everolimus
• Nivolumab
• Pazopanib
• Temsirolimus (Category 1 for poor-prognosis patients)

Management of Oligometastatic Disease

For patients with resectable primary RCC and synchronous oligometastatic disease: 1

• Surgical metastasectomy for amenable sites (lung, bone, brain)
• Stereotactic body radiation therapy (SBRT) as alternative to surgery 1
• Ablative techniques for patients not candidates for metastasectomy 1

Site-Specific Metastatic Management

Brain metastases: 1

• Corticosteroids for temporary symptom relief
• Whole brain radiation therapy (20-30 Gy in 4-10 fractions) for symptom control
• Stereotactic radiosurgery (SRS) with or without WBRT for single unresectable metastasis in good-prognosis patients
• Immune checkpoint inhibitor-based combination therapy preferred for first-line systemic treatment 4

Bone metastases: 1

• Radiation therapy for symptomatic lesions
• Bisphosphonates or RANK ligand inhibitors for prevention of skeletal-related events
• Cabozantinib-containing regimens may be preferred for systemic treatment 4

Critical Pitfalls to Avoid

• Do not perform cytoreductive nephrectomy in intermediate/poor-risk patients with asymptomatic primary tumors and high-volume metastases who require immediate systemic therapy 1, 4
• Do not use ablative techniques without understanding their higher local recurrence rates compared to surgery 1
• Do not delay tissue sampling in patients with surgically unresectable tumors - histology confirmation is essential to guide systemic therapy 1
• Monitor for hepatotoxicity with sunitinib - fatal liver failure has been observed; check liver function tests at baseline and during each cycle 6
• Monitor cardiovascular function with VEGF-targeted agents - myocardial infarction, heart failure, and decreased LVEF can occur 6