Abstract
The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor‐specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities.
Highlights
Patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) have 22% to 47% risk of developing a subsequent urothelial carcinoma of the bladder (UCB) within 2 years.[1]
By intraluminal seeding or intraepithelial spread, cancer cells from the primary UTUC implant in the bladder wall and develop into a UCB resulting in clonally related tumors.[3]
We performed a systematic review of the literature on the clonal relationship between UTUC and paired UCB and found that 94% of the cases originated from the same progenitor cell.[4]
Summary
Patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) have 22% to 47% risk of developing a subsequent urothelial carcinoma of the bladder (UCB) within 2 years.[1] Two hypotheses have been proposed for this increased risk. The entire urinary tract of patients with urothelial carcinoma undergoes a “field change,” priming the tissue for independent transformations.[2] Upper and lower tract tumors develop independently from one another and are not clonally related. By intraluminal seeding or intraepithelial spread, cancer cells from the primary UTUC implant in the bladder wall and develop into a UCB resulting in clonally related tumors.[3] Recently, we performed a systematic review of the literature on the clonal relationship between UTUC and paired UCB and found that 94% of the cases originated from the same progenitor cell.[4] the molecular techniques used differed largely over time and research groups, plus only a limited number of studies used comprehensive large-scale DNA sequencing techniques, which enables more conclusive assessment of a clonal relation between these two entities
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