Distinct patterns and behaviour of urothelial carcinoma with respect to anatomical location: how molecular biomarkers can augment clinico-pathological predictors in upper urinary tract tumours

Abstract

Upper urinary tract urothelial carcinoma (UTUC) shares many similarities with bladder-UC, but there is strong evidence on a clinical, aetiological, epidemiological and genetic level that key differences exist. In this review, we aim to highlight how UTUC differs from bladder-UC and report on the utility of molecular markers in the diagnosis and management of UTUC. A systematic literature search was conducted using the Medline and Embase databases and specific keyword combinations: 'urothelial carcinoma', 'bladder cancer', 'transitional cell carcinoma', 'upper tract', 'upper urinary tract', 'genetics', 'prognosis' and 'biomarkers'. UTUC has specific acquired (e.g. Balkans nephropathy, phenacetin abuse) and genetic hereditary non-polyposis colorectal cancer risk factors compared with bladder-UC. In general, the molecular biology of UC is broadly similar, irrespective of location in the urinary tract. However, there are distinct genetic (microsatellite instability) and epigenetic (hypermethylation) differences between some UTUC and bladder-UC. Clinical-pathological variables (e.g. hydronephrosis, tumour architecture, tumour location, stage and grade) have independent predictive power in UTUC, but tissue and urinary biomarkers can improve the clinical prediction of recurrence, invasion and survival in UTUC, though the evidence level is weak. UTUC shares many similarities with bladder-UC, but there is strong evidence that they should be considered as distinct urothelial entities. Prospective multi-institutional studies investigating molecular markers are urgently needed to augment clinic-pathological predictors in UTUC.