The Emergence of Precision Urologic Oncology: A Collaborative Review on Biomarker-driven Therapeutics

Abstract

Context: Biomarker-driven cancer therapy, also referred to as precision oncology, has received increasing attention for its promise of improving patient outcomes by defining subsets of patients more likely to respond to various therapies.

Objective: In this collaborative review article, we examine recent literature regarding biomarker-driven therapeutics in urologic oncology, to better define the state of the field, explore the current evidence supporting utility of this approach, and gauge potential for the future.

Evidence acquisition: We reviewed relevant literature, with a particular focus on recent studies about targeted therapy, predictors of response, and biomarker development.

Evidence synthesis: The recent advances in molecular profiling have led to a rapid expansion of potential biomarkers and predictive information for patients with urologic malignancies. Across disease states, distinct molecular subtypes of cancers have been identified, with the potential to inform choices of management strategy. Biomarkers predicting response to standard therapies (such as platinum-based chemotherapy) are emerging. In several malignancies (particularly renal cell carcinoma and castration-resistant prostate cancer), targeted therapy against commonly altered signaling pathways has emerged as standard of care. Finally, targeted therapy against alterations present in rare patients (less than 2%) across diseases has the potential to drastically alter patterns of care and choices of therapeutic options.

Conclusions: Precision medicine has the highest potential to impact the care of patients. Prospective studies in the setting of clinical trials and standard of care therapy will help define reliable predictive biomarkers and new therapeutic targets leading to real improvement in patient outcomes.

Patient summary: Precision oncology uses molecular information (DNA and RNA) from the individual and the tumor to match the right patient with the right treatment. Tremendous strides have been made in defining the molecular underpinnings of urologic malignancies and understanding how these predict response to treatment-this represents the future of urologic oncology.

Keywords: Genomics; Mutations; Precision Medicine; Sequencing.

Fig. 1

Landscape of precision urologic oncology. Relevant biological pathways, therapeutic targets, and therapies are highlighted for prostate cancer (left), urothelial cancer (center), and renal cell carcinoma (right). Therapeutics are outlined in red; biological pathways and targets are shown in yellow. Immunotherapy approaches using checkpoint inhibitors (top) may be applicable across disease histologies, with the most current evidence in renal and urothelial cancer. AR = androgen receptor; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; mTOR = mechanistic target of rapamycin; PD-1 = programmed cell death protein 1; PDGF = platelet-derived growth factor; PD-L1 = programmed death-ligand 1; TKIs = tyrosine kinase inhibitors; VEGF = vascular endothelial growth factor.