Abstract
Introduction: Upper tract urinary cancer recurrence (UTUCR) after radical cystectomy (RC) is outcome-limiting. Surgical recommendations on intraoperative performance of frozen section analysis (FSA) and management of positive ureteral margin (PUM) are lacking. Methods: 634 RC cases were identified (2010–2018). In patients with PUM, sequential ureteral resections up to a negative margin were performed. We investigated the accuracy of FSA, significance of PUM, and identified risk factors (RFs) to stratify patients for UTUCR. Results: FSA was performed in 355 patients, including a total of 693 ureters. FSA sensitivity was 0.93 and specificity 0.99. PUM conversion was possible in 52 (91.2%) cases. UTUCR occurred in 17 (4.8%) patients. Identified UTUCR RFs are non-muscle invasive bladder carcinoma (NMIBC) (OR 3.8, 95% confidence intervals [CI] 1.4–10.2, p = 0.008), multifocal bladder cancer in cystectomy specimen (OR 4.7, CI 1.1–20.8, p = 0.042), and recurrent NMIBC (OR 4.1, CI 1.5–10.9, p = 0.006). Risk-group stratification showed a six-fold increase in UTUCR risk (low-to high-risk). Conclusion: FSA is a sensitive and specific method to identify PUM. UTUCR occurs significantly more often in patients with recurrent, multifocal NMIBC at the time of RC. Patients can be risk stratified for UTUCR. In case of NMIBC-PUM, surgeons can safely opt for a kidney preserving strategy.
References
1.
Ferlay
J
, Steliarova-Foucher
E
, Lortet-Tieulent
J
, Rosso
S
, Coebergh
JW
, Comber
H
, Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012
. Eur J Can
. 2013 Apr
;49
(6
):1374
–403
.2.
Leal
J
, Luengo-Fernandez
R
, Sullivan
R
, Witjes
JA
. Economic burden of bladder cancer across the European union
. Eur Urol
. 2016 Mar
;69
(3
):438
–47
. .3.
Alfred Witjes
J
, Lebret
T
, Compérat
EM
, Cowan
NC
, De Santis
M
, Bruins
HM
, Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer
. Eur Urol
. 2017 Mar
;71
(3
):462
–75
.4.
Gakis
G
, Black
PC
, Bochner
BH
, Boorjian
SA
, Stenzl
A
, Thalmann
GN
, Systematic review on the fate of the remnant urothelium after radical cystectomy
. Eur Urol
. 2017 Apr
;71
(4
):545
–57
.5.
Picozzi
S
, Ricci
C
, Gaeta
M
, Ratti
D
, Macchi
A
, Casellato
S
, Upper urinary tract recurrence following radical cystectomy for bladder cancer: a meta-analysis on 13,185 patients
. J Urol
. 2012 Dec
;188
(6
):2046
–54
.6.
Schumacher
MC
, Scholz
M
, Weise
ES
, Fleischmann
A
, Thalmann
GN
, Studer
UE
. Is there an indication for frozen section examination of the ureteral margins during cystectomy for transitional cell carcinoma of the bladder?
J Urol
. 2006
;176
(6
):2409
–13
. .7.
Hoang
AN
, Agarwal
PK
, Walton-Diaz
A
, Wood
CG
, Metwalli
AR
, Kassouf
W
, Clinical significance of ureteric “skip lesions” at the time of radical cystectomy: the M.D. Anderson experience and literature review
. BJU Int
. 2014 May
;113
(5b
):E28
–33
.8.
Leow
JJ
, Martin-Doyle
W
, Rajagopal
PS
, Patel
CG
, Anderson
EM
, Rothman
AT
, Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials
. Eur Urol
. 2014 Jul
;66
(1
):42
–54
.9.
Peduzzi
P
, Concato
J
, Feinstein
AR
, Holford
TR
. Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates
. J Clin Epidemiol
. 1995 Dec
;48
(12
):1503
–10
. .10.
Volkmer
BG
, Schnoeller
T
, Kuefer
R
, Gust
K
, Finter
F
, Hautmann
RE
. Upper urinary tract recurrence after radical cystectomy for bladder cancer: who is at risk?
J Urol
. 2009 Dec
;182
(6
):2632
–7
. .11.
Kenworthy
P
, Tanguay
S
, Dinney
CP
. The risk of upper tract recurrence following cystectomy in patients with transitional cell carcinoma involving the distal ureter
. J Urol
. 1996 Feb
;155
(2
):501
–3
. .12.
Solsona
E
, Iborra
I
, Rubio
J
, Casanova
J
, Dumont
R
, Monrós
JL
. Late oncological occurrences following radical cystectomy in patients with bladder cancer
. Eur Urol
. 2003 May
;43
(5
):489
–94
. .13.
Lee
SE
, Byun
SS
, Hong
SK
, Chang
IH
, Kim
YJ
, Gill
MC
, Significance of cancer involvement at the ureteral margin detected on routine frozen section analysis during radical cystectomy
. Urol Int
. 2006
;77
(1
):13
–7
.14.
Raj
GV
, Tal
R
, Vickers
A
, Bochner
BH
, Serio
A
, Donat
SM
, Significance of intraoperative ureteral evaluation at radical cystectomy for urothelial cancer
. Cancer
. 2006 Nov 1
;107
(9
):2167
–72
.15.
Furukawa
J
, Miyake
H
, Hara
I
, Takenaka
A
, Fujisawa
M
. Upper urinary tract recurrence following radical cystectomy for bladder cancer
. Int J Urol
. 2007 Jun
;14
(6
):496
–9
. .16.
Sanderson
KM
, Cai
J
, Miranda
G
, Skinner
DG
, Stein
JP
. Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup
. J Urol
. 2007 Jun
;177
(6
):2088
–94
. .17.
Tran
W
, Serio
AM
, Raj
GV
, Dalbagni
G
, Vickers
AJ
, Bochner
BH
, Longitudinal risk of upper tract recurrence following radical cystectomy for urothelial cancer and the potential implications for long-term surveillance
. J Urol
. 2008 Jan
;179
(1
):96
–100
.18.
Tollefson
MK
, Blute
ML
, Farmer
SA
, Frank
I
. Significance of distal ureteral margin at radical cystectomy for urothelial carcinoma
. J Urol
. 2010 Jan
;183
(1
):81
–6
. .19.
Umbreit
EC
, Crispen
PL
, Shimko
MS
, Farmer
SA
, Blute
ML
, Frank
I
. Multifactorial, site-specific recurrence model after radical cystectomy for urothelial carcinoma
. Cancer
. 2010 Jul 15
;116
(14
):3399
–407
. .20.
Gakis
G
, Schilling
D
, Perner
S
, Schwentner
C
, Sievert
KD
, Stenzl
A
. Sequential resection of malignant ureteral margins at radical cystectomy: a critical assessment of the value of frozen section analysis
. World J Urol
. 2011 Aug
;29
(4
):451
–6
. .21.
Takayanagi
A
, Masumori
N
, Takahashi
A
, Takagi
Y
, Tsukamoto
T
. Upper urinary tract recurrence after radical cystectomy for bladder cancer: incidence and risk factors
. Int J Urol
. 2012 Mar
;19
(3
):229
–33
. .22.
Perlis
N
, Turker
P
, Bostrom
PJ
, Kuk
C
, Mirtti
T
, Kulkarni
G
, Upper urinary tract and urethral recurrences following radical cystectomy: review of risk factors and outcomes between centres with different follow-up protocols
. World J Urol
. 2013 Feb
;31
(1
):161
–7
.23.
Kim
SH
, Yang
HK
, Lee
JH
, Lee
ES
. A retrospective analysis of incidence and its associated risk factors of upper urinary tract recurrence following radical cystectomy for bladder cancer with transitional cell carcinoma: the significance of local pelvic recurrence and positive lymph node
. PloS One
. 2014
;9
(5
):e96467
. .24.
Loeser
A
, Katzenberger
T
, Vergho
DC
, Kocot
A
, Burger
M
, Riedmiller
H
. Frozen section analysis of ureteral margins in patients undergoing radical cystectomy for bladder cancer: differential impact of carcinoma in situ in the bladder on reliability and impact on tumour recurrence in the upper urinary tract
. Urol Int
. 2014
;92
(1
):50
–4
. .25.
Kim
HS
, Moon
KC
, Jeong
CW
, Kwak
C
, Kim
HH
, Ku
JH
. The clinical significance of intra-operative ureteral frozen section analysis at radical cystectomy for urothelial carcinoma of the bladder
. World J Urol
. 2015 Mar
;33
(3
):359
–65
. .26.
Satkunasivam
R
, Hu
B
, Metcalfe
C
, Ghodoussipour
SB
, Aron
M
, Cai
J
, Utility and significance of ureteric frozen section analysis during radical cystectomy
. BJU Int
. 2016 Mar
;117
(3
):463
–8
.27.
Kiss
B
, Furrer
MA
, Wuethrich
PY
, Burkhard
FC
, Thalmann
GN
, Roth
B
. Stenting prior to cystectomy is an independent risk factor for upper urinary tract recurrence
. J Urol
. 2017 Dec
;198
(6
):1263
–8
. .28.
Laukhtina
E
, Rajwa
P
, Mori
K
, Moschini
M
, D’Andrea
D
, Abufaraj
M
, Accuracy of frozen section analysis of urethral and ureteral margins during radical cystectomy for bladder cancer: a systematic review and diagnostic meta-analysis
. Eur Urol Focus
. 2021 Jun 11
.29.
Shanks
JH
, Iczkowski
KA
. Divergent differentiation in urothelial carcinoma and other bladder cancer subtypes with selected mimics
. Histopathol
. 2009 Jun
;54
(7
):885
–900
. .30.
Hakozaki
K
, Kikuchi
E
, Fukumoto
K
, Shirotake
S
, Miyazaki
Y
, Maeda
T
, Significance of a frozen section analysis of the ureteral margin in bladder cancer patients treated with radical cystectomy and neoadjuvant chemotherapy
. Med Oncol
. 2017 Oct 23
;34
(12
):187
.31.
Kocot
A
, Kalogirou
C
, Vergho
D
, Riedmiller
H
. Long-term results of ileal ureteric replacement: a 25-year single-centre experience
. BJU Int
. 2017 Aug
;120
(2
):273
–9
. .32.
Rouprêt
M
, Babjuk
M
, Burger
M
, Capoun
O
, Cohen
D
, Compérat
EM
, European association of urology guidelines on upper urinary tract urothelial carcinoma: 2020 update
. Eur Urol
. 2021 Jan
;79
(1
):62
–79
.© 2022 S. Karger AG, Basel
2022
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
