Surgical extirpation is the primary treatment for localized renal cell carcinoma. Patients with a single kidney, bilateral lesions, or significant medical renal disease should be considered for partial nephrectomy. Patients harboring a small tumor with a normal contralateral kidney and good kidney function are also candidates for partial nephrectomy, while radical nephrectomy is indicated in patients with cancers larger than 7 cm and those in whom partial nephrectomy is not technically feasible. Radiofrequency and cryosurgical ablation are alternative options instead of surgery in select patients with tumors less than 3–4 cm with similar risk of metastatic progression but higher risk of local recurrence. Active surveillance is warranted in select patients (significant comorbidity, short life expectancy) and appears safe with low risk of 5-year systemic progression. Percutaneous biopsy can provide tumor histology and grade to help guide treatment decisions.
Cytotoxic chemotherapy has no role in the treatment of metastatic renal cell carcinoma. Historically, cytokine-based immunotherapies, such as interferon-alpha and interleukin-2, produced partial response rates of 15–20% and 15–35%, respectively (Table 39–2). Responders tended to have lower tumor burden, metastatic disease confined to the lung, and a high-performance status. Two randomized trials demonstrating a survival benefit of cytoreductive nephrectomy followed by systemic interferon-alpha compared with the use of systemic therapy alone led to the widespread adoption of cytoreductive nephrectomy. Patients most likely to benefit from cytoreduction were those with good performance status, lung only metastases, and good prognostic features.
The treatment of metastatic renal cell carcinoma has evolved rapidly over the last decade. Presently, management strategies are based on tumor histology and patient risk (favorable, intermediate, and poor). Several targeted medications, specifically VEGF, Raf-kinase, and mTOR inhibitors, are effective (40–60% response rates) in patients with advanced kidney cancer (Table 39–2). These oral agents, which include sunitinib, pazopanib, cabozantinib, axitinib, and sorafenib, are generally well tolerated and particularly active for clear cell carcinoma. The optimal timing and combination of these agents remain to be determined. Sunitinib is approved for adjuvant use after complete surgical resection in patients with adverse pathologic features. The mTOR inhibitors everolimus and temsirolimus are approved for use in patients with prior anti-VEGF therapy, as is the combination of lenvatinib and everolimus. Nivolumab is an approved anti-PD-1 immunotherapy for treating metastatic disease that has progressed despite antiangiogenic therapy. Nivolumab in combination with the anti-CTLA4 immunotherapy ipilimumab (objective response rate 42%, complete response rate 9%) and pembrolizumab in combination with the VEGF inhibitor axitinib (objective response rate 59%, complete response rate 5.8%) have proved superior to sunitinib in previously untreated intermediate- and poor-risk metastatic clear cell renal cell carcinoma and are considered the standard first-line treatment for this patient population (Table 39–2).
The utilization of cytoreductive nephrectomy in combination with contemporary agents has decreased in response to the results of CARMENA in which patients with intermediate and poor-risk clear cell renal carcinoma had similar survival following cytoreductive nephrectomy with or without sunitinib and adoption of combination immunotherapy regimens (nivolumab plus ipilimumab, pembrolizumab plus axitinib). Still, there remains a role for cytoreductive surgery in select patients with intermediate-risk disease.