What are the treatment options for Renal Cell Carcinoma (RCC)?

Treatment Options for Renal Cell Carcinoma (RCC)

The treatment of renal cell carcinoma should be tailored according to disease stage, with surgery being the standard of care for localized disease, while advanced or metastatic RCC requires a combination of surgical and systemic approaches including targeted therapies and immunotherapy. 1

Localized Disease Management

Surgical Options

• Partial nephrectomy is recommended for all T1 tumors (<7 cm) if negative margins can be obtained and morbidity risk is acceptable 1
• Laparoscopic radical nephrectomy is preferred for organ-confined RCC (T1-T2N0M0) when partial nephrectomy is not feasible 1
• Open radical nephrectomy remains the standard of care for locally advanced RCC (T3 and T4) 1
• Routine adrenalectomy and extensive lymph node dissection are not recommended when imaging shows no evidence of involvement 1

Alternative Approaches

• Ablative treatments (radiofrequency ablation, cryotherapy) are alternatives for elderly patients with small cortical tumors (≤3 cm), hereditary RCC, or multiple bilateral tumors 1
• Active surveillance can be considered for patients ≥75 years with significant comorbidities and solid renal tumors <4 cm 1

Adjuvant Therapy

• Currently, there is no universally recommended adjuvant treatment, though clinical trials are ongoing 1
• Patients with localized disease should be encouraged to participate in clinical trials 1

Metastatic Disease Management

Surgical Interventions

• Cytoreductive nephrectomy is recommended for patients with good performance status and large primary tumors or symptomatic primary lesions 1
• Metastasectomy may benefit select patients with solitary or easily accessible pulmonary metastases, solitary resectable intra-abdominal metastases, or those with a long disease-free interval after nephrectomy 1

Systemic Therapy for Clear Cell RCC (most common subtype)

First-line Treatment

• For good and intermediate risk patients:

  • Sunitinib (50 mg daily, 4 weeks on/2 weeks off) 1, 2
  • Pazopanib 1
  • Bevacizumab combined with interferon-alpha 1
  • Immune checkpoint inhibitor (ICI) combinations including ipilimumab-nivolumab, axitinib-pembrolizumab, cabozantinib-nivolumab, and lenvatinib-pembrolizumab for patients with sarcomatoid histology 1

• For poor risk patients:

  • Temsirolimus is the only drug with level 1 evidence of activity 1
  • ICI-based therapies are preferred for sarcomatoid histology 1

Second-line Treatment

• After VEGF pathway inhibitors:

  • Everolimus 1
  • Sorafenib 1
  • Belzutifan for previously treated patients 1

• After cytokines:

  • Axitinib 1
  • Sunitinib 1
  • Sorafenib 1

Systemic Therapy for Non-Clear Cell RCC

Papillary RCC

• Cabozantinib is the preferred first-line monotherapy 1
• Alternative options include sunitinib, pembrolizumab, or combination therapies like lenvatinib-pembrolizumab and cabozantinib-nivolumab 1

Other Non-Clear Cell Subtypes

• Clinical trial enrollment is recommended 1
• For chromophobe RCC: sunitinib, pazopanib, lenvatinib-everolimus, or everolimus 1
• For collecting duct carcinomas: cisplatin-based chemotherapy 1
• For sarcomatoid histology: ICI-based therapies 1

Supportive Care

• Radiotherapy for palliation, especially for symptomatic bone metastases 1
• Stereotactic radiotherapy for brain metastases 1
• Zoledronic acid or denosumab can be considered for patients with bone metastases 1

Follow-up Recommendations

Localized Disease

• Risk-based follow-up approach with imaging for 2 years after nephrectomy 1
• For high-risk disease: CT scans of thorax and abdomen every 3-6 months for the first 2 years 1
• For low-risk disease: annual CT scans are likely sufficient 1
• Continuation of follow-up for up to 5 years can be considered 1

Advanced/Metastatic Disease

• CT scans every 2-4 months during systemic therapy to assess response 1
• Clinical judgment in addition to radiological assessment is required when determining treatment modifications 1

Common Pitfalls and Caveats

• Not all patients with metastatic disease benefit from cytoreductive nephrectomy; careful patient selection is crucial 1
• Some RCCs have an indolent course; a period of observation before starting treatment should be considered for metastatic disease 1
• Response Evaluation Criteria in Solid Tumors (RECIST) alone should not dictate treatment interruption or modification 1
• The use of further PD-(L)1-targeted therapy after progression on first-line PD-1-targeted therapy is not recommended 1