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04-08-2016 | Renal cell carcinoma | Article

Medical treatment of renal cancer: new horizons

Authors:
Basma Greef, Tim Eisen

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 These targeted treatments superseded immunotherapy with interleukin-2 and interferon.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.

Br J Cancer 2016; 115: 505–516. doi:10.1038/bjc.2016.230

Keywords: systemic therapy; metastatic renal cell carcinoma; T-cell checkpoint inhibitors; tyrosine kinase inhibitors

Renal cell carcinoma (RCC) represents 2–3% of all adult cancers (Rini et al, 2009a). It is the seventh most common malignancy in men, and the ninth in women (Rini et al, 2009a) with 10 144 new cases and 4252 deaths in the United Kingdom per year (Cancer Research UK, 2016). Risk factors include hypertension, smoking, obesity and end-stage renal disease. With increasing use of radiological investigations, there has been a steady increase in the rate of incidental diagnosis, which now accounts for half of all new RCC cases. A third of cases present with metastatic disease at diagnosis (Gupta et al, 2008) and a third of those undergoing surgery for early stage disease will relapse, after a median of 1.9 years (Stewart et al, 2014).

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