[Current approaches to the first-line treatment of clear-cell renal cell carcinoma]

The medical treatment of renal cell carcinoma has been revolutionized in recent years, thanks to translation of our increasingly accurate knowledge on the molecular pathogenesis of this tumor, and of its clear cell histology in particular, into an accelerated drug development, and then into everyday's clinical practice. In this review, starting with the pathogenesis of clear cell renal cell carcinoma, we shall address the results of the clinical trials that led to the registration of seven targeted agents for this disease once orphan of active treatments, taking into account the different prognostic groups in which the patients suffering from it can be divided. Finally, we shall discuss the complex and controversial issue of the ideal timing to start a systemic treatment, a critical and still highly debated topic. All major international guidelines agree on the standard first line therapeutic options, which are represented by sunitinib, bevacizumab (associated with interferon-α) and pazopanib for patients with good or intermediate risk features, and temsirolimus for poor-risk patients. All these agents proved able to prolong progression-free survival within randomized phase III trials. The use of an observation period, before starting a systemic treatment, seems also reasonable, at least in the more indolent tumors and in patients with a better prognosis, even if the topic is still controversial. Finally, the individualization of therapy and the proper conduct of the same is essential for a successful outcome of the treatment.