Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)
The early detection and diagnosis of RCC remains a challenge to oncologists and presents a significant barrier to reducing mortality due to this cancer. Roughly 30% of RCC cases present with metastatic disease at the time of initial diagnosis . Although this percentage has declined in recent years due to increased incidental detection of small renal masses, the mortality rate from RCC has remained steadfastly unchanged . This suggests that RCC with lethal potential are not being identified sufficiently early to prevent metastatic spread, and this presents the single most significant opportunity to reduce death due to RCC. Patients with metastatic RCC have a much poorer prognosis compared with patients with early-stage disease, with a 5-year survival rate of 23% for stage IV disease as compared to a 5-year survival rate of 96% for stage I presentation .
The use of early detection biomarkers remains in development, but interesting tools are on the horizon. New generations of biomarkers that examine novel substrates such as microRNA (miRNA, miR), proteomic, and metabolomic profiles, with the potential to measure hundreds or more elements simultaneously as a biomarker “profile,” are being investigated intensely as tools for RCC early detection and diagnosis. The results have been encouraging [6, 7], but await full clinical validation.
Several early detection serum and urinary biomarkers have been reported as a first step toward a clinically relevant RCC detection assay. Noninvasive detection methods are promising given the increased frequency of detection of RCC from incidental findings on imaging. In one recent study, analysis of RCC cases revealed elevated plasma levels of N-methyltransferase (NNMT), L-plastin (LCP1), and nonmetastatic cells 1 protein (NM23A) . A three-marker assay was developed with good positive and negative predictive value for RCC, although results of this study remain unvalidated. Examination of urinary samples from newly diagnosed RCC patients and matched controls identified 86 peptides more frequently found in RCC, most of which were fragments of collagen chains. An assay using these peptides was developed and then validated using an independent set of patients, enabling differentiation of RCC from control with excellent discriminative accuracy (AUC of 0.92) . These assays may help indicate the presence of a kidney primary malignancy, although they need to be further validated and studied in a diagnostic capacity.
Metastatic RCC consists of a heterogeneous group of cancers. This creates incredible challenges to prediction of prognosis and response to different therapeutics. Biomarkers have their most immediate potential in RCC to demystify the heterogeneity and classify RCC into meaningful subgroups. Ultimately, having a rational biological signature from which to draw prognostic or predictive information, yet with low cost and minimal specimens from patients, would be invaluable. In the last decade, the emergence of multiple FDA-approved targeted therapies gives promise to patients with advanced RCC; however, it also adds complexity in the effort of tailoring each agent to different individuals in appropriate sequence. Despite increased understanding of the underlying tumor biology of RCC and its variant histologies (which arguably comprise highly distinct disease entities), the current TNM staging and subtyping of RCC give inadequate insight to refine current algorithms for treatment selection, disease monitoring, and management. The identification and utilization of novel biomarkers for prognosis and prediction of response are important approaches for personalized RCC treatment.
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