Introduction: Intravesical recurrence after treatment of primary upper urinary tract urothelial carcinomas (UUT-UCs) is common. While intravesical instillation is widely used to prevent recurrence after transurethral resection for primary bladder tumors, there is still no consensus on the prophylactic capability of intravesical chemotherapy in preventing bladder tumor recurrence after surgery for UUT-UCs. Methods: A meta-analysis of the published results of clinical trials was performed to compare radical surgery alone or surgery plus postoperative intravesical chemotherapy. The primary end point was to determine the percentage of patients with recurrence in the different groups. Results: Our study includes five trials with recurrence information on 614 patients. During follow-up, 55 of 268 (20.5%) patients who received postoperative instillation had bladder recurrence compared to 127 of 346 (36.7%) patients who had no adjuvant treatment - a decrease of 41% in the odds of recurrence with chemotherapy (odds ratio 0.48, 95% confidence interval 0.33-0.69, p = 0.0001). No serious adverse events were reported. Subgroup analyses were temporarily unavailable. Conclusions: Postoperative intravesical chemotherapy significantly decreases the risk of bladder recurrence after nephroureterectomy for primary UUT-UCs. Postoperative intravesical instillation is considered the treatment of choice after nephroureterectomy.

Keywords:
Bladder cancer, Intravesical chemotherapy, Meta-analysis , Nephroureterectomy, Upper urinary tract urothelial carcinoma
1.
Munoz JJ, Ellison LM: Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 2000;164:1523-1525.
2.
Ploeg M, Aben KK, Kiemeney LA: The present and future burden of urinary bladder cancer in the world. World J Urol 2009;27:289-293.
3.
Landis SH, Murray T, Bolden S, Wingo PA: Cancer statistics, 1998. CA Cancer J Clin 1998;48:6-29.
4.
Margulis V, Shariat SF, Matin SF, Kamat AM, Zigeuner R, Kikuchi E, Lotan Y, Weizer A, Raman JD, Wood CG: Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer 2009;115:1224-1233.
5.
Cummings KB: Nephroureterectomy: rationale in the management of transitional cell carcinoma of the upper urinary tract. Urol Clin North Am 1980;7:569-578.
6.
Matsui Y, Utsunomiya N, Ichioka K, Ueda N, Yoshimura K, Terai A, Arai Y: Risk factors for subsequent development of bladder cancer after primary transitional cell carcinoma of the upper urinary tract. Urology 2005;65:279-283.
7.
Terakawa T, Miyake H, Muramaki M, Takenaka A, Hara I, Fujisawa M: Risk factors for intravesical recurrence after surgical management of transitional cell carcinoma of the upper urinary tract. Urology 2008;71:123-127.
8.
Novara G, De Marco V, Dalpiaz O, Gottardo F, Bouygues V, Galfano A, Martignoni G, Patard JJ, Artibani W, Ficarra V: Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract. BJU Int 2008;101:1368-1374.
9.
Raman JD, Ng CK, Boorjian SA, Vaughan ED Jr, Sosa RE, Scherr DS: Bladder cancer after managing upper urinary tract transitional cell carcinoma: predictive factors and pathology. BJU Int 2005;96:1031-1035.
10.
Zigeuner RE, Hutterer G, Chromecki T, Rehak P, Langner C: Bladder tumour development after urothelial carcinoma of the upper urinary tract is related to primary tumour location. BJU Int 2006;98:1181-1186.
11.
Huang WW, Huang HY, Liao AC, Shiue YL, Tai HL, Lin CM, Wang YH, Lin CN, Shen KH, Li CF: Primary urothelial carcinoma of the upper tract: important clinicopathological factors predicting bladder recurrence after surgical resection. Pathol Int 2009;59:642-649.
12.
Morioka M, Jo Y, Furukawa Y, Kinugawa K, Sone A, Matsuki T, Kobayashi T, Fujii T, Tanaka H: Prognostic factors for survival and bladder recurrence in transitional cell carcinoma of the upper urinary tract. Int J Urol 2001;8:366-373.
13.
Miyake H, Hara I, Kamidono S, Eto H: Multifocal transitional cell carcinoma of the bladder and upper urinary tract: molecular screening of clonal origin by characterizing CD44 alternative splicing patterns. J Urol 2004;172:1127-1129.
14.
Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Huguet-Perez J, Vicente-Rodriguez J: Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups. J Urol 2000;164:1183-1187.
15.
Habuchi T, Takahashi R, Yamada H, Kakehi Y, Sugiyama T, Yoshida O: Metachronous multifocal development of urothelial cancers by intraluminal seeding. Lancet 1993;342:1087-1088.
16.
Hafner C, Knuechel R, Zanardo L, Dietmaier W, Blaszyk H, Cheville J, Hofstaedter F, Hartmann A: Evidence for oligoclonality and tumor spread by intraluminal seeding in multifocal urothelial carcinomas of the upper and lower urinary tract. Oncogene 2001;20:4910-4915.
17.
Catto JW, Hartmann A, Stoehr R, Bolderson E, Rehman I, Rosario DJ, Hamdy FC, Meuth M: Multifocal urothelial cancers with the mutator phenotype are of monoclonal origin and require panurothelial treatment for tumor clearance. J Urol 2006;175:2323-2330.
18.
Takahashi T, Kakehi Y, Mitsumori K, Akao T, Terachi T, Kato T, Ogawa O, Habuchi T: Distinct microsatellite alterations in upper urinary tract tumors and subsequent bladder tumors. J Urol 2001;165:672-677.
19.
Badalament RA, Herr HW, Wong GY, Gnecco C, Pinsky CM, Whitmore WF Jr, Fair WR, Oettgen HF: A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer. J Clin Oncol 1987;5:441-449.
20.
Sylvester RJ, Oosterlinck W, Witjes JA: The schedule and duration of intravesical chemotherapy in patients with non-muscle-invasive bladder cancer: a systematic review of the published results of randomized clinical trials. Eur Urol 2008;53:709-719.
21.
O'Brien T, Ray E, Singh R, Coker B, Beard R: Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: a prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial). Eur Urol 2011;60:703-710.
22.
Wu WJ, Ke HL, Yang YH, Li CC, Chou YH, Huang CH: Should patients with primary upper urinary tract cancer receive prophylactic intravesical chemotherapy after nephroureterectomy? J Urol 2010;183:56-61.
23.
Tian J, Li C, Ma J, Xiao Z, Shou J, Xiao Z: A matched case-control study of postoperative intravesical chemotherapy for upper urinary tract tumor. J Clin Urol 2011;26:927-929.
24.
Ito A, Satoh M, Shintaku I, Ishidoya S, Arai Y: Intravesical instillation of pirarubicin reduces the incidence of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: final result of a phase II prospective randomized trial. J Urol 2012;187:220-221.
25.
Sakamoto N, Naito S, Kumazawa J, Ariyoshi A, Osada Y, Omoto T, Fujisawa Y, Morita I, Yamashita H: Prophylactic intravesical instillation of mitomycin C and cytosine arabinoside for prevention of recurrent bladder tumors following surgery for upper urinary tract tumors: a prospective randomized study. Int J Urol 2001;8:212-216.
26.
Kudoh T, Motomura F, Saitoh F, Kogawa T, Suzuki T: Prophylactic intravesical BCG for bladder tumor after surgery of upper tract urothelial carcinoma (in Japanese). Nihon Hinyokika Gakkai Zasshi 1990;81:1857-1860.
27.
Tari K, Satake I, Kojima S, Negishi T, Yoshida K, Nakame Y, Kanaoya F, Horiuchi S, Saito T, Owada F, et al: Prophylactic intravesical chemotherapy in bladder tumors after surgery of upper tract urothelial carcinoma (in Japanese). Hinyokika Kiyo 1987;33:852-856.
28.
Azemar MD, Comperat E, Richard F, Cussenot O, Roupret M: Bladder recurrence after surgery for upper urinary tract urothelial cell carcinoma: frequency, risk factors, and surveillance. Urol Oncol 2009;29:130-136.
29.
Sylvester RJ, Oosterlinck W, van der Meijden AP: A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol 2004;171:2186-2190; quiz 2435.
© 2013 S. Karger AG, Basel
2013
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.