How could molecular biology modify the management of upper urinary tract tumours?

BACKGROUND Upper urinary tract urothelial carcinomas (UUT-UCs) account for only 5-10% of urothelial carcinomas and the gold standard treatment is open radical nephroureterectomy. Strong differences exist regarding tumor behaviour between the upper and the lower urinary tract. OBJECTIVE To demonstrate how the current knowledge in molecular biology of UUT-UCs is likely to modify the management of these tumours. ACQUISITION OF EVIDENCE A MEDLINE search was performed on UUT-UC using the following terms: urinary tract cancer; urothelial carcinomas; upper urinary tract; molecular markers; renal pelvis; ureter; ureteroscopy; nephroureterectomy; adjuvant treatment; neoadjuvant treatment; recurrence; risk factors and survival. EVIDENCE SYNTHESIS Conservative surgery for low-risk UUT-UCs allows for preservation of the upper urinary renal unit, while sparing the patient the morbidity associated with open surgery. Such surgical strategy might be more appropriate in tumors displaying certain molecular markers: microsatellite instability, E-cadherin, MET, Aurora-A, and Ki-67. These markers could help to identify more candidates to nephron-sparing treatment without compromising the oncologic outcome. Susceptibility means an increase in risk conferred by one or more polymorphisms (allele types) of a given gene or genes, which expose the individual to the genotoxic effects of environmental carcinogens. The variant allele SULT1A1*2 with reduced sulfotransferase activity and the T allele of rs9642880 on chromosome 8q24 enhance the risk of UUT-UCs. If an at-risk genetic profile could be established, it might be possible to prevent urothelial carcinomas in some patients. CONCLUSIONS Surgical practice is gradually moving towards minimally invasive techniques which spare the functional unity of the kidney and urinary tract. The ongoing identification of distinct carcinogenic mechanisms for UUT-UCs might open the way to specific treatments adapted to the molecular pattern of each tumor. The next era might hopefully be that of chemoprevention.