What are the treatment options for a patient diagnosed with renal cancer?

Treatment Options for Renal Cancer

For localized renal cell carcinoma, partial nephrectomy is the definitive first-line treatment for tumors <7 cm, preserving renal function while achieving equivalent cancer-free survival to radical nephrectomy. 1

Localized Disease (Stages I-III)

Small Renal Masses (T1a: ≤4 cm)

• Partial nephrectomy (nephron-sparing surgery) is the gold standard, offering >94% 5-year cancer-specific survival while preserving renal function and reducing cardiovascular morbidity compared to radical nephrectomy 1, 2
• Laparoscopic or robotic approaches achieve equivalent oncologic outcomes to open surgery with reduced morbidity 1
• Thermal ablation (radiofrequency, microwave, or cryoablation) is appropriate for tumors ≤3 cm in frail patients, those with high surgical risk, compromised renal function, solitary kidney, or hereditary RCC 1
• Renal biopsy must be performed before ablation to confirm malignancy and histologic subtype 1, 3
• Active surveillance is recommended for elderly patients with significant comorbidities, short life expectancy, and solid tumors <40 mm, with biopsy to confirm diagnosis 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, with no tumor size limitation in patients with compromised renal function or bilateral disease 1
• Laparoscopic radical nephrectomy is the preferred option for T2 tumors >7 cm when nephron-sparing surgery is not feasible 1
• Radical nephrectomy includes perifascial resection of kidney, perirenal fat, and regional lymph nodes 1

Locally Advanced Disease (T3-T4)

• Open radical nephrectomy is standard of care, though laparoscopic approach can be considered in selected cases 1
• Radical nephrectomy is preferred when tumor extends into the inferior vena cava, with approximately 50% achieving long-term survival 1
• Lymph node dissection is recommended for palpable or CT-detected enlarged nodes and provides prognostic information, though it is not therapeutic 1
• Ipsilateral adrenalectomy should be considered only for large upper-pole tumors or abnormal-appearing adrenal glands on imaging 1

Metastatic/Advanced Disease (Stage IV)

Cytoreductive Nephrectomy

• Cytoreductive nephrectomy is recommended in patients with good performance status before systemic therapy 1
• Do not perform cytoreductive nephrectomy in intermediate- and poor-risk patients with asymptomatic primary tumors requiring immediate systemic therapy 1, 4

First-Line Systemic Therapy by Risk Group

Good and Intermediate-Risk Patients:

• VEGF-targeted tyrosine kinase inhibitors (sunitinib, tivozanib) or bevacizumab plus interferon-α are recommended options, achieving tumor response rates of 42-71% and median overall survival of 46-56 months 1, 5, 2
• Sunitinib 50 mg orally once daily on a 4-weeks-on/2-weeks-off schedule is FDA-approved for advanced RCC 5

Intermediate and Poor-Risk Patients:

• Nivolumab plus ipilimumab combination immunotherapy is the recommended first-line treatment, but not for good-risk patients 1
• Cabozantinib is EMA-approved for intermediate and poor-risk groups 1
• Temsirolimus should be proposed to poor-risk patients according to MSKCC classification 1

Second-Line Systemic Therapy

• Following TKI failure, nivolumab or cabozantinib is recommended 1
• Lenvatinib plus everolimus is FDA/EMA-approved following TKI failure and after nivolumab/ipilimumab combination 1
• For patients already treated with two TKIs, either nivolumab or cabozantinib is recommended 1

Metastasectomy and Local Therapies

• Metastasectomy may be considered for patients with solitary metastasis 1
• Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy should be considered for good-prognosis patients with single unresectable brain metastasis 1
• Image-guided radiotherapy (VMAT or SBRT) enables high-dose delivery for unresectable local disease 1

Palliative Radiotherapy

• Radiotherapy is effective for palliation of symptomatic bone or brain metastases and prevention of progression in critical sites 1, 4
• For brain metastases, corticosteroids provide temporary symptom relief, and whole-brain radiotherapy 20-30 Gy in 4-10 fractions is recommended 1, 4
• For spinal cord compression, surgery followed by postoperative radiotherapy improves survival and maintains ambulation compared to radiation alone 1

Critical Diagnostic Requirements

• Contrast-enhanced CT of chest, abdomen, and pelvis is essential for accurate staging 1, 3, 4
• Laboratory evaluation must include CBC, comprehensive metabolic panel (calcium, LDH, creatinine), coagulation profile, and urinalysis 1
• Core needle biopsy is mandatory before ablative therapies and systemic treatment in metastatic disease to confirm histology 1, 3
• Abdominal MRI evaluates inferior vena cava involvement or serves as alternative when contrast CT is contraindicated 1, 3

Common Pitfalls to Avoid

• Never perform radical nephrectomy when nephron-sparing surgery is achievable, as radical nephrectomy increases risk of chronic kidney disease and cardiovascular mortality 1
• In elderly patients, calculate creatinine clearance using Cockcroft-Gault or MDRD equations rather than relying on serum creatinine alone, as renal function declines 1% per year after age 30-40 4
• Do not routinely perform bone scan or brain imaging unless patient has elevated alkaline phosphatase, bone pain, or neurological symptoms 1
• FDG-PET is not recommended for routine RCC diagnosis 3
• Lymph node dissection provides prognostic but not therapeutic benefit, as virtually all node-positive patients relapse with distant metastases 1