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

Abstract

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.

Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial

“…The extent to which such tumors are clonally related to UTUC has varied in previous studies. [9][10][11][12] The pattern here may suggest that, particularly, later-forming tumors could be the result of a new, in situ oncogenic process; notwithstanding, such temporal relationships remain to be fully elucidated.…”

Case Report: Step-by-step procedures for total intracorporeal laparoscopic kidney autotransplantation in a patient with distal high-risk upper tract urothelial carcinoma

“…Although diagnostic URS biopsy is an important component in the diagnosis of UTUC, allowing for patient risk stratification, it can present a technical challenge. As invasive preoperative diagnostic modalities are associated with the risk of urinary bladder recurrence (UBR), URS biopsy is a significant risk factor for UBR in UTUC ( 16 ). Thus, we instead used a flexible ureteroscope to probe the renal pelvis and ureter of the hypothermic isolated kidney to further clarify the presence of tumour metastasis and implantation, which was a feasible approach.…”

Upper Tract Urothelial Carcinoma (UTUC) Diagnosis and Risk Stratification: A Comprehensive Review

“…Diagnostic URS without biopsy was not associated with worse IVRFS [7]. Table 1 summarizes the studies assessing the association between URS, IVR (intravesical recurrence), and RFS (recurrence-free survival) [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. A study on 143 patients demonstrated a pathological phenotype-specific association between pre-operation URS and oncological outcomes, as the subgroup of patients with non-papillary and ≥pT3 UTUC had poorer overall and progression-free survival [23].…”