Management of Renal Cell Carcinoma

Diagnosis and Staging

The European Association of Urology recommends laboratory examinations including serum creatinine, hemoglobin, leukocyte and platelet counts, lymphocyte to neutrophil ratio, lactate dehydrogenase, CRP, and serum-corrected calcium tests to confirm suspicion of RCC 2
Contrast-enhanced chest, abdominal, and pelvic CT are recommended for accurate staging by the European Association of Urology 2
Renal tumor core biopsy is recommended before ablative therapies and in patients with metastatic disease before starting systemic treatment by the European Association of Urology 2
The UICC TNM 8 staging system should be used for proper classification by the European Association of Urology 2

Partial nephrectomy (PN) is recommended as the first-line approach to preserve renal function in patients with T1 tumors (<7 cm) by the European Association of Urology 2, 3
Laparoscopic radical nephrectomy (RN) is recommended if PN is not feasible by the European Association of Urology 2
For patients with compromised renal function or bilateral tumors, PN is recommended regardless of tumor size by the European Association of Urology 2

Cytoreductive nephrectomy (CN) is recommended in patients with good performance status by the European Association of Urology 2
CN should be avoided in intermediate and poor-risk patients with asymptomatic primary tumors when systemic treatment is required by the European Association of Urology 2, 4
VEGF-targeted agents and tyrosine kinase inhibitors (TKIs) are recommended options for good and intermediate-risk patients by the European Association of Urology 2
Immune checkpoint inhibitor (ICI) in combination with a VEGFR TKI is recommended for good and intermediate-risk patients by the European Society for Medical Oncology 3
Ipilimumab plus nivolumab is a preferred option for intermediate or poor-risk disease by the American Society of Clinical Oncology 4, 3

Definitive metastasis-directed therapies including surgical resection (metastasectomy), ablative measures, or radiotherapy may be offered for low-volume metastatic disease by the American Society of Clinical Oncology 5
Bone-directed radiation for symptomatic lesions is recommended by the American Society of Clinical Oncology 4, 6
Bone resorption inhibitor (bisphosphonate or RANKL inhibitor) when there is clinical concern for fracture or skeletal-related events is recommended by the American Society of Clinical Oncology 4, 6
Cabozantinib-containing regimens may be preferred for systemic treatment in patients with bone metastases by the American Society of Clinical Oncology 4, 6
Brain-directed local therapy with radiation therapy and/or surgery is recommended for brain metastases by the European Association of Urology 4, 6
Immune checkpoint inhibitor-based combination therapy is preferred for first-line systemic treatment in patients with brain metastases by the American Society of Clinical Oncology 4, 6
Immune checkpoint inhibitor-based combination first-line treatment (ipilimumab plus nivolumab, or alternatively, an immune checkpoint inhibitor plus a TKI) is recommended for patients with sarcomatoid features by the American Society of Clinical Oncology 4, 6

For patients on immunotherapy who experience limited disease progression (e.g., one site of progression), local therapy (radiation, thermal ablation, excision) may be offered, and immunotherapy may be continued by the American Society of Clinical Oncology 5
Risk stratification using validated prognostic models such as MSKCC or IMDC criteria should guide treatment decisions by the European Society for Medical Oncology 3