Predictive biomarkers in oncologic uropathology

Abstract

Background: Tumors of the genitourinary system are common. In recent years, our understanding of their molecular background and therefore the number of potential predictive biomarkers has massively increased. Objectives: The aim of the current work is to give an overview of recent (molecular) developments and predictive biomarkers in urologic oncology and to give a perspective of what might become relevant in the future of the field. Material and methods: We considered the recent literature and study data and combined it with our own expertise in tumors of the urinary system, kidneys, and prostate. Results and conclusions: The molecular subtypes of muscle-invasive urothelial bladder cancer (MIBC) hold a predictive and prognostic significance and correlate with clinicopathological features. Immune therapy with checkpoint inhibitors (CPI) has a major role in urothelial carcinoma (UC), but also in renal cell carcinoma and a subgroup of prostate cancers. The first-line use in UC is restricted to PD-L1-“positive” cases (≥IC2/3, CPS ≥ 10). Further predictive markers are currently under evaluation, while the predictive significance of tumor mutational burden (TMB) is under debate. In addition to a subgroup of renal cell carcinomas, a subgroup of prostate carcinomas with alterations in the DNA repair system might benefit from a customized therapy approach (PARP inhibitors, platin-containing chemotherapy). The multitude of potentially therapy-relevant molecular alterations and related predictive biomarkers calls for the implementation of sophisticated molecular analyses in daily routine. This will lead to an even more rapid dynamic in the field of genitourinary pathology.