What is the recommended treatment for a patient with pT3a clear cell renal cell carcinoma?

Treatment of pT3a Clear Cell Renal Cell Carcinoma

Open radical nephrectomy with the goal of obtaining negative margins is the standard of care for pT3a clear cell renal cell carcinoma. 1

Surgical Management

• Open radical nephrectomy remains the standard of care for locally advanced RCC (T3 and T4), although a laparoscopic approach can be considered in select cases 1, 2
• The primary goal of surgery should be to obtain negative margins to maximize oncological outcomes 1, 2
• Systematic adrenalectomy is not recommended when abdominal CT shows no evidence of adrenal invasion 1
• Extensive lymph node dissection is not routinely required unless there is clinical evidence of lymph node involvement 1, 3
• For tumors with venous thrombus (common in T3a disease), surgical intervention to remove the thrombus should be considered, with the approach depending on thrombus level 1, 2

Risk Assessment

• pT3a clear cell RCC is considered high risk with a 5-year metastasis-free survival of approximately 31.2% for patients with a SSIGN score ≥6 1, 2
• Risk factors that should be evaluated include:
  • Nuclear grade (grade 3-4 increases risk) 1, 2
  • Tumor size (≥10 cm increases risk) 1, 2
  • Histological tumor necrosis 1, 2

Adjuvant Therapy Considerations

• Currently, there is no universally recommended adjuvant treatment following surgery for localized disease 1
• Multiple adjuvant trials are ongoing, and inclusion of patients with localized disease into clinical trials should be encouraged 1
• Sunitinib is FDA-approved for adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy, though its use remains controversial 4
• The S-TRAC trial showed improved disease-free survival with adjuvant sunitinib, but without overall survival benefit 2
• The European Medicines Agency has not approved adjuvant therapy with VEGFR-targeted agents due to the imbalance between risk and clinical benefit 2

Special Considerations

• Neoadjuvant approaches are still experimental and should not be proposed outside of clinical trials 1, 2
• Attempting to downsize venous tumor thrombi with systemic targeted therapy before surgery is not recommended 1, 2
• In cases where metastatic disease is present at diagnosis, cytoreductive nephrectomy may still be considered in patients with good performance status and limited volume of metastatic disease 1
• For patients with solitary kidney or compromised renal function, partial nephrectomy may be considered even for pT3a disease, as recent evidence suggests comparable oncologic outcomes with better preservation of renal function 5

Follow-up Recommendations

• Patients with pT3a clear cell RCC should undergo intensified follow-up due to the high risk of recurrence 1
• For patients with positive surgical margins, follow-up should be particularly rigorous, especially in cases of upstaged pT3a disease 1

Systemic Treatment Options for Recurrent/Metastatic Disease

• If metastatic disease develops, first-line treatment options include:
  • For good or intermediate prognosis: VEGF-targeted therapies (sunitinib, pazopanib) or immunotherapy combinations 1, 6
  • Nivolumab plus ipilimumab has demonstrated improved overall survival in intermediate and poor-risk patients with metastatic RCC 6

By following this treatment algorithm, patients with pT3a clear cell renal cell carcinoma can receive optimal care that balances oncologic control with preservation of renal function when possible.