Synchronous and metachronous urothelial carcinoma of the upper urinary tract and the bladder: Are they clonally related? A systematic review.

ABSTRACT

PURPOSE: Following radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC), intravesical recurrence (IVR) is found in 22% to 47% of patients. Patients with a primary urothelial carcinoma of the bladder (UCB) have an increased risk of a future UTUC (1%-5%). Paired UTUC and UCB might represent clonally related tumors due to intraluminal seeding of tumor cells or might be separate entities of urothelial carcinoma caused by field cancerization. We systematically reviewed all the relevant literature to address the possible clonal relation of UTUC and paired UCB. MATERIALS AND METHODS: MEDLINE, EMBASE, and COCHRANE databases were systematically searched for relevant citations published between January 2000 and July 2019. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Of 5038 citations identified, 86 full papers were screened, and 9 studies met the inclusion criteria. RESULTS: The populations studied and the molecular techniques used to assess clonality of UTUC and paired UCB differed largely over time. Eight studies reported on primary UTUC and meta- or synchronous IVR without a history of UCB. A total of 118 tumors (55 UTUC and 63 IVR) from 49 patients were included, of which 94% seemed to be clonally related. Five studies reported on primary UCB and subsequent UTUC with a total of 61 tumors (30 UCB and 31 UTUC) from 14 patients; a possible clonal origin was identified for 85% of the tumors. CONCLUSION: Taking into account the limitations of microsatellite technology in comparison to Next Generation Sequencing and currently accepted concepts of tumor heterogeneity and evolution, this systematic review shows that most, if not all, UTUC and paired UCB likely are clonally related.