Urinary bladder recurrences following ureteroscopic biopsies of upper tract urothelial cancers:a multi-centre observational study with genomic assessment for clonality

Background and aims: Urinary 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.Methods: Patients 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).Results: Of 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.Conclusions: Ureteroscopic biopsy of UTUC is a significant risk factor for UBR. Qualitative clonality assessment showed identical mutational signatures between primary UTUC and UBR.