Abstract
Though the definition of a biomarkers can vary, they are broadly considered quantifiable characteristics of biological processes that have the potential to influence or predict disease outcomes and treatment responses. In the current era of precision and personalized medicine, biomarkers have become quite common in both the clinical and research setting. However, unlike in other genitourinary malignancies such as prostate, bladder, and testis cancer, biomarkers for renal cell carcinoma (RCC) have historically had a limited use. Indeed, a recent analysis of genomic sequencing data from over 750 RCC tumors found a low prevalence of targetable alterations compared to other malignancy types. Such findings have contributed to the to this lack of clinically meaningful biomarkers for patients with RCC.
For patients with RCC, the assessment of recurrence risk and response to treatments is largely based on clinical and pathologic features. Various for systems have been developed which take into account these factors and offer providers and patients prognostic information, including the Memorial Sloan Kettering recurrence nomogram. Although useful, such tools rely on variables such as tumor grade, tumor necrosis, and performance status which may be subject to inter-observer variability and might not account for individual tumor biology.
The advent of novel systemic therapies in the past two decades has caused a paradigm shift in the treatment of advanced and metastatic RCC and has brought upon a renewed focus on the usage of biomarkers. Immune checkpoint inhibitors are now an integral component to the therapeutic armamentarium for this disease process and are often used in combination with other targeted systemic therapies. Despite these advances, survival for patients is still relatively poor. The plethora of treatment choices and an unpredictable disease course with variable responses to these treatments make optimal therapeutic pathways elusive. Thus, there has been a focused effort to identify biomarkers to aid in this endeavor.
This chapter will address the current landscape of predictive biomarkers for advanced RCC. As will be discussed, there scope of work that has been done on this topic is quite broad from histopathologic, to genomic, to microbiome-related biomarkers. While many of the undermentioned topics are investigational and do not yet have any widespread clinical utility, they provide a useful framework for which further research can be based.