Presented by: Mohammad Zuaiter MD
University Hospitals Coventry & Warwickshire NHS Trust

Introduction

Radical nephroureterectomy with the excision of the bladder cuff remains the gold standard for managing high risk upper urinary tract urothelial carcinoma (UTUC). Pre-operative management of high risk (UTUC), however, is yet not standardized as obtaining a histological diagnosis and drainage of the obstructed upper tract may or may not be carried out pre-operatively. We review lower urinary tract recurrence rates post radical nephroureterectomy for high grade (UTUC) at our institution over a 7-year period with particular attention to pre-operative stenting of upper tract system.

Materials

In this retrospective observational study, a total of 109 patients underwent radical nephroureterectomy from the year 2015 to 2022. Of these cases, 65 patients were eligible for the study. All eligible patients had high grade (UTUC) on post-operative histopathology with at least one follow-up cystoscopy done within 12 months post nephroureterectomy. Patients with low grade (UTUC) or non-urothelial tumours on histopathology, or who had simple cystectomy done prior to radical nephroureterectomy, or had a history of high grade lower tract urothelial carcinoma, or had no follow up cystoscopy, or died within 3 months post-operatively were excluded from the study. Post nephroureterectomy lower urinary tract recurrence and histopathology were observed. Time taken for first lower tract recurrence to occur was also reviewed. Patients were divided into two main groups, those who were stented pre-operatively vs. those who were not. Furthermore, patients with hydronephrosis (n=48) were subdivided into two distinct subgroups, those who had hydronephrosis and were stented pre-operatively (n=15) vs. patients who had hydronephrosis but were not pre-stented (n=33). Post nephroureterectomy lower urinary tract recurrence was then compared in both subgroups. All patients underwent either laparoscopic or robot assisted radical nephroureterectomy. Pre-operative biopsy was done percutaneously in two cases with the rest having ureteroscopic biopsies (n=21). Data were evaluated for significance by two-tailed unpaired t test, with P ≤ 0.05 considered significant. Calculations were performed using GraphPad Dotmatics software (Graph-Pad Software, Inc., San Diego, CA).

Results

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Nineteen (29.2%) of the 65 patients had at least one lower urinary tract recurrence within 36 months post-operatively. Eleven patients (57.9%) out of 19 pre-stented had post-operative lower tract recurrence compared to eight (17.4%) out of 46 patients who were not pre-stented (p-value =0.0008). Fifty three percent out of those who had hydronephrosis and stent insertion pre-operatively developed lower urinary tract recurrence compared to (24.2%) who had hydronephrosis but were not pre-stented (p-value =0.048). Mean time to first recurrence was 10.1 months. Mean time to first recurrence in patients who were pre-stented was 6.1 months compared to 16 months in those not pre-stented (p-value =0.0144). Majority of the recurrences (73.6%) occurred in the first 12 months post-operatively. Fifty-two percent of those who underwent a pre-operative biopsy plus stent insertion had post-operative lower tract recurrence compared to (16.7%) who were not biopsied pre-operatively (p-value =0.002). Sixteen patients out of those who had hydronephrosis (33.3%) had recurrence compared to only three patients (17.6%) who did not have hydronephrosis. Ten patients (52.6%) out of the lower tract recurrence cases were Ta high grade (TCC), while five (26.3%) were T1 high grade (TCC), two (10.5%) were T2 high grade (TCC), and one had isolated carcinoma in situ. Nineteen (29.2%) of the 65 cases had a ureteral stent inserted pre-operatively. Twenty-three (36.4%) of the 65 patients underwent pre-operative diagnostic biopsy. Sixteen (24.6%) cases had pre-operative biopsy plus stent insertion pre-operatively. Forty-eight patients (73.8%) had hydronephrosis. Thirty-five patients had left sided radical nephroureterectomy. Mean age at diagnosis was 70.8 years, male to female ratio was 1.5 to 1, with visible haematuria being the most common presentation (69.2.5%), followed by incidental radiographic finding and visible haematuria (13.8%) & (9.2%), respectively, while two patients presented with non-visible haematuria and two more with acute kidney injury, in addition to one patient who presented with weight loss. Only 37 cases (56.9%) had pre-operative cytology checked with (35.1%) being positive. Mean pre- and post-operative creatinine were 98.9 and 131.9 mmol/L, respectively. The most common tumour site occurrences were pelvis & calyces 33 occasions, followed by mid ureter 22 occurrences, distal ureter 19 occurrences, and proximal ureter 17 occurrences. All tumours were high grade urothelial carcinoma with a mean size of 4.35 cm, and multifocal in (32.3%) of the cases. Regarding post-operative histology, twenty patients (30.8%) had Ta high grade (TCC), four (6.2%) had T1 high grade TCC, eleven (16.9%) had T2 high grade TCC, twenty-three (35.4%) had T3 high grade TCC, five (7.7%) had T4 high grade TCC, one had isolated carcinoma in situ (CIS) and one more had T0. Nine patients had variant histology while 46 had tumour invasion. Thirty-six patients (55.4%) had associated upper tract CIS while one had isolated upper tract (CIS). Out of 24 lymph nodes dissected only 2 were found positive.

Conclusion

In the context of high grade (UTUC), pre-nephroureterectomy ureteral stenting increases the overall risk for post operative lower tract recurrence and shortens the time taken for first postoperative bladder recurrence to occur significantly. Furthermore, the combination of hydronephrosis and pre-operative stenting almost doubles the overall risk for postoperative bladder recurrence compared to hydronephrosis alone.

Funding

None.

Lead Authors

Mohammad Zuaiter, MD
University Hospitals Coventry & Warwickshire

Co-Authors

Saifelislam Awida, MD
University Hospitals Coventry & Warwickshire

Baidar Yousif Khalabazyane, MD
University Hospitals Coventry & Warwickshire

Aran Nanthakumar, MD
University Hospitals Coventry & Warwickshire

Kumar Priyadarshi, MD
University Hospitals Coventry & Warwickshire