• Thineskrishna Anbarasan, Sheikh Nissar, Julie Turbitt, Kathryn Walls, Sarah McLuckie, Caroline Clark, Jean-Christophe Bourdon, Joel Tracey, Susan Bray, Atlaf Shamsuddin, Jason Alcorn, Sunjay Jain, Robert Hislop, Chandra Shekhar Biyani, and Ghulam Nabi.
• College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK.
• Scot Med J. 2023 Feb 1; 68 (1): 4134-13.

Background And AimsUrinary bladder recurrences (UBRs) after radical nephroureterectomy (RNUx) are a known challenge in patients with upper-tract urothelial cancers (UTUCs). We aim to assess factors associated with UBR and clonal-relatedness with resected UTUC.MethodsPatients who underwent RNUx for UTUC between 1998 and 2015 in five institutions were identified. Clonal relatedness between primary UTUC and subsequent UBR in a sub-cohort was assessed using next-generation sequencing. A Kaplan-Meier curve was used to assess differences in UBR between two groups (with or without ureteroscopic biopsy).ResultsOf 267 patients with complete records, 73 (27.3%) had UBR during follow-up. The five-year UBR-free survival in all patients was 64.7%. The five-year UBR-free-survival was inferior in patients who underwent URS biopsy compared with patients who did not undergo ureteroscopic biopsy (49.9% vs 76.4%, p < 0.001). History of bladder tumour (HR, 95% CI; 2.94, 1.73-5.00, p < 0.001), ureteroscopic biopsy (HR, 95% CI; 2.21, 1.38-3.53, p = 0.001) and preoperative urine cytology ≥C3 (HR, 95% CI; 2.06, 1.24-3.40, p = 0.005) were independently associated with UBR. Patients with ureteroscopic biopsy (n = 3/5) showed identical mutational changes for common genes (TP53 and FGFR3) between primary UTUC and subsequent UBR.ConclusionsUreteroscopic biopsy of UTUC is a significant risk factor for UBR. Qualitative clonality assessment showed identical mutational signatures between primary UTUC and UBR.

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