The Role of the Systemic Inflammatory Response as a Biomarker in Immunotherapy for Renal Cell Cancer

Abstract

Treatment of metastatic renal cell cancer (RCC) has entered a new paradigm since the development of tyrosine kinase inhibitors such as sorafenib (Nexavar®) and sunitinib (Sutent®). Despite these advances, immunotherapy, the traditional mainstay of treatment, is not yet obsolete. Immunotherapy offers the possibility of a complete response for a small number of patients with favorable disease factors. However, immunotherapy is a toxic treatment, with a significant impact on quality of life in comparison with a relatively modest survival advantage for most. As such, the search for a biomarker to select patients for immunotherapy and to monitor their progress still remains a clinical and research goal for those involved in treating patients with metastatic renal cancer.

At present, performance status and a number of prognostic scores incorporating performance status and laboratory variables are the most widely used indicators of suitability for immunotherapy. More recently, the histological expression of carbonic anhydrase IX has been reported as a biomarker of response to interleukin (IL)-2 immunotherapy.

C-reactive protein (CRP) is an acute-phase protein synthesized as part of the systemic inflammatory response. It is readily measured by standardized assays and is reliable, without variability for age, sex, or bodyweight. The presence of an elevated CRP is a prognostic indicator in a number of solid tumors, both in localized and metastatic disease. In advanced renal cancer, the Glasgow Prognostic Score, which is based on elevated CRP and low albumin, has shown prognostic value. CRP is also superior to the widely used performance status in predicting survival for patients treated with either interferon (IFN)-α or IL-2. As such, CRP is an increasingly exciting biomarker for predicting outcomes in immunotherapy. Currently, no other biomarker has been applicable for use in both IFNα and IL-2 immunotherapy. More recently, changes in CRP kinetics have shown promise as a predictive tool, although more research is required. Use of CRP as a biomarker can improve stratification of patients with metastatic renal cancer, allowing the patients less likely to benefit from immunotherapy to avoid a potentially toxic treatment. The ongoing selection of patients based on biomarkers should enable continued research on the optimum dose and timing of immunotherapy while managing toxicity and optimizing outcomes.