Medical treatment of renal cancer: new horizons

Abstract

Renal cell carcinoma (RCC) makes up 2-3% of adult cancers. The introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors in the mid-2000s radically changed the management of RCC. These targeted treatments superseded immunotherapy with interleukin-2 and interferon. The pendulum now appears to be shifting back towards immunotherapy, with the evidence of prolonged overall survival of patients with metastatic RCC on treatment with the anti-programmed cell death 1 ligand monoclonal antibody, nivolumab. Clinical prognostic criteria aid prediction of relapse risk for resected localised disease. Unfortunately, for patients at high risk of relapse, no adjuvant treatment has yet shown benefit, although further trials are yet to report. Clinical prognostic models also have a role in the management of advanced disease; now there is a pressing need for predictive biomarkers to direct therapy. Treatment selection for metastatic disease is currently based on histology, prognostic group and patient preference based on side effect profile. In this article, we review the current medical and surgical management of localised, oligometastatic and advanced RCC, including side effect management and the evidence base for management of poor-risk and non-clear cell disease. We discuss recent results from clinical trials and how these are likely to shape future practice and a renaissance of immunotherapy for renal cell cancer.

Figure 1

Mechanism of action of treatments for RCC. Abbreviations: CTLA4=cytotoxic T-lymphocyte-associated antigen 4; HGF=hepatocyte growth factor; PDGF=platelet-derived growth factor; PDGFR=platelet-derived growth factor receptor; PD-1=programmed cell death 1; PDL-1=programmed cell death ligand 1; VEGF=vascular endothelial growth factor; VEGFR=vascular endothelial growth factor receptor.

Figure 2

Kaplan–Meier curve for overall survival in the Checkmate025 study (Reproduced with permission from Motzer et al (2015a)). Abbreviations: CI=confidence interval; NE=not estimable.