European Association of Urology Guidelines for Systemic Therapy in Metastatic Renal Cell Carcinoma: What is Recommended and Why?

Metastatic renal cell carcinoma (mRCC) is largely resistant to conventional chemotherapy, hormonal therapy, and cytokine therapy and is associated with a poor prognosis. The European Association of Urology (EAU) recently published updated guidelines, with specific recommendations for treating mRCC. The EAU recommendations were based on recent clinical study data, which demonstrated the superiority of newer targeted therapies over interferon-α (IFN-α). mRCC is a highly vascularised tumour, characterised in the majority of cases by over-production of angiogenic peptides such as vascular endothelial growth factor. The targeted therapies selectively inhibit proteins whose functions include the stimulation of angiogenesis; two of these therapies, sunitinib and sorafenib, are currently approved in the European Union for use in mRCC. Reflecting the improved options now available, the updated EAU guidelines recommend using sunitinib, an orally administered antiangiogenic drug that selectively targets several receptors whose ligands are up-regulated in RCC, as first-line therapy for mRCC in good- and intermediate-risk patients. This recommendation is based on compelling data from a phase 3 trial that demonstrated longer progression-free survival and greater objective response rates for untreated patients with mRCC receiving sunitinib than for those receiving IFN-α. Other recommendations include using sorafenib as second-line therapy for mRCC and considering temsirolimus as first-line therapy for poor-risk patients with mRCC. Clinical studies investigating these agents, both alone and in combination, are ongoing. We review the clinical studies that form the basis of the EAU guidelines to gain an insight into the rationale behind the updated recommendations.