[50 years of renal cell carcinoma]

In the past 50 years, many knowledge gaps regarding renal cell carcinoma (RCC) have been closed. A pathological tumour classification has been developed and different histological subtypes are known today. In clear cell RCC, the (mutated) von Hippel-Lindau gene located on chromosome 3 is highly important. Operative therapy of non-metastatic RCC has evolved from radical nephrectomy to less radical techniques including procedures sparing the adrenal gland as well as nephron-sparing surgery. Surgical procedures are increasingly performed using laparoscopic or robot-assisted approaches. Even less invasive techniques such as cryoablation, radiofrequency ablation or active surveillance are applied for small renal masses, if indicated. Metastatic RCC is most commonly treated by systemic therapy. Chemotherapy has no effect in RCC. For more than 20 years, cytokine therapy was the standard of care for metastatic RCC. Mutations of the von Hippel-Lindau gene associated with accumulation of hypoxia-inducible factor, followed by increased transcription of vascular endothelial growth factor, provided the scientific rationale for the successful use of tyrosine kinase inhibitors, mTOR inhibitors, and anti-VEGF antibodies introduced in 2006. The development of checkpoint inhibitors has changed the systemic treatment of RCC in yet another relevant manner.