Diagnostic and Prognostic Markers for Renal Cell Carcinoma

Diagnostic Markers

PAX8 and CAIX are common markers recommended for the histological evaluation of clear cell renal cell carcinoma (ccRCC) 1
The diagnosis of metastatic ccRCC should ideally involve comparison of tissue acquired outside the primary disease site with the primary histology 1
Histological evaluation with these markers is particularly important when diagnostic material from the primary tumor is not available 1

The International Metastatic RCC Database Consortium (IMDC) system is the gold standard for risk assessment in metastatic disease, and includes six factors: Karnofsky performance status <80%, hemoglobin below the lower limit of normal, time from diagnosis to treatment <1 year, corrected calcium above the upper limit of normal, platelets above the upper limit of normal, and neutrophils above the upper limit of normal 3
The IMDC system is applicable in subsequent lines of therapy and in non-clear cell histology 3
PD-L1 has a negative prognostic role when elevated, although its predictive value remains controversial 3
Tumor expression of PD-L1 can identify patients who benefit from combination immunotherapy 3

Inhibitors of PD-1 in combination with VEGFR-targeted therapy or CTLA-4 inhibition have improved overall survival 7
Lenvatinib-pembrolizumab, axitinib-pembrolizumab, or cabozantinib-nivolumab are recommended for first-line treatment of advanced ccRCC, regardless of IMDC risk group 7
Ipilimumab-nivolumab is recommended as an equivalent therapeutic option for first-line treatment of intermediate and poor-risk IMDC disease 7

For patients with bone metastases, regimens containing cabozantinib may be preferred 6
Combination immunotherapy based on checkpoint inhibitors is preferred for first-line systemic treatment in patients with brain metastases 6
First-line treatment with combination immunotherapy (ipilimumab plus nivolumab, or alternatively, a checkpoint inhibitor plus a TKI) is recommended for patients with sarcomatoid features 6

Not performing biopsy of the renal mass before ablative treatments can lead to treatment of benign lesions, as up to 30% of T1a masses are benign 5
Discrepancies in PD-L1 expression between the primary tumor and metastases have been reported, limiting its utility as a biomarker 3
The radiographic diagnosis of metastatic ccRCC can be applied in selected circumstances, such as when a previous diagnosis of renal carcinoma has been established or when metastatic tissue is not easily accessible for biopsy 1