Background: Guidelines support the use of neoadjuvant (NAC) and adjuvant (AC) chemotherapy in muscle-invasive bladder cancer. However, data from North America reported the underutilization of NAC in favor of AC despite the lower level of scientific evidence supporting AC. We aimed to assess current practice patterns of NAC and AC in -Germany. Methods: A 15-question online survey was developed and sent via email newsletters to members of the -German Association of Urology and of the German Society of Residents in Urology in October 2016 to analyze current practice patterns. Results: The survey yielded 141 individual responses from 61 different German urology departments. Eighty-nine (69.0%) and 119 (93.0%) participants were stated to regularly use NAC and AC respectively. The number of participants who were stated to use NAC and AC regularly was not associated with the type of institution (academic vs. nonacademic), number of hospital beds, and number of cystectomies performed annually. Gemcitabine/cisplatin combination chemotherapy was named as the primarily used NAC regimen by 80 (95%) respondents. The median number of administered cycles was 3 for NAC and 4 for AC. In the case of cisplatin ineligibility, combination chemotherapy with gemcitabine/carboplatin was the most common regimen. Respondents stated that chemotherapy was generally administered by urologists (81% for NAC and 85% for AC). Conclusions: Our survey of current practice shows a high acceptance rate of NAC in Germany, which was independent of the type of institution. Although the scientific level of evidence for AC is lower, it still seems to be more widely accepted than NAC. NAC and AC were generally administered by urologists.

Keywords:
Adjuvant chemotherapy, Bladder cancer, Neoadjuvant chemotherapy, Gemcitabine, Cisplatin, Survey
1.
Ferlay J, Soerjomataram I, Dikshit R, et al: Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136:E359–E386.
2.
Alfred Witjes J, Lebret T, Comperat EM, et al: Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol 2017; 71: 462–475.
3.
Cho KS, Seo JW, Park SJ, et al: The risk factor for urethral recurrence after radical cystectomy in patients with transitional cell carcinoma of the bladder. Urol Int 2009; 82: 306–311.
4.
Ghoneim MA, Abdel-Latif M, el-Mekresh M, et al: Radical cystectomy for carcinoma of the bladder: 2,720 consecutive cases 5 years later. J Urol 2008; 180: 121–127.
5.
May M, Helke C, Nitzke T, et al: Survival rates after radical cystectomy according to tumor stage of bladder carcinoma at first presentation. Urol Int 2004; 72: 103–111.
6.
Schiffmann J, Sun M, Gandaglia G, et al: Use of adjuvant chemotherapy in radical cystectomy patients aged >65 years: a population-based study from the surveillance epidemiology and end results (SEER)-medicare database. Minerva Urol Nefrol 2017; 69: 173–180.
7.
David KA, Milowsky MI, Ritchey J, et al: Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the national cancer data base. J Urol 2007; 178: 451–454.
8.
Leow JJ, Martin-Doyle W, Rajagopal PS, et al: Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol 2014; 66: 42–54.
9.
Eysenbach G: Improving the quality of web surveys: the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). J Med Internet Res 2004; 6:e34.
10.
Galsky MD, Hahn NM, Rosenberg J, et al: A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol 2011; 12: 211–214.
11.
Keegan KA, Zaid HB, Patel SG, Chang SS: Increasing utilization of neoadjuvant chemotherapy for muscle-invasive bladder cancer in the United States. Curr Urol Rep 2014; 15: 394.
12.
Di Trapani E, Sanchez-Salas R, Gandaglia G, et al: A nomogram predicting the cancer-specific mortality in patients eligible for radical cystectomy evaluating clinical data and neoadjuvant cisplatinum-based chemotherapy. World J Urol 2016; 34: 207–213.
13.
Kim SH, Seo HK, Shin HC, et al: Trends in the use of chemotherapy before and after radical cystectomy in patients with muscle-invasive bladder cancer in Korea. J Korean Med Sci 2015; 30: 1150–1156.
14.
Feifer A, Taylor JM, Shouery M, et al: Multi-institutional quality-of-care initiative for nonmetastatic, muscle-invasive, transitional cell carcinoma of the bladder: phase I. J Clin Oncol 2011; 29: 240.
15.
Reardon ZD, Patel SG, Zaid HB, et al: Trends in the use of perioperative chemotherapy for localized and locally advanced muscle-invasive bladder cancer: a sign of changing tides. Eur Urol 2015; 67: 165–170.
16.
Cowan NG, Chen Y, Downs TM, et al: Neoadjuvant chemotherapy use in bladder cancer: a survey of current practice and opinions. Adv Urol 2014; 2014: 746298.
17.
Herr HW, Dotan Z, Donat SM, Bajorin DF: Defining optimal therapy for muscle invasive bladder cancer. J Urol 2007; 177: 437–443.
18.
Raj GV, Karavadia S, Schlomer B, et al: Contemporary use of perioperative cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer. Cancer 2011; 117: 276–282.
19.
Grossman HB, Natale RB, Tangen CM, et al: Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003; 349: 859–866.
20.
Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet 1999; 354: 533–540.
21.
Lee CT, Madii R, Daignault S, et al: Cystectomy delay more than 3 months from initial bladder cancer diagnosis results in decreased disease specific and overall survival. J Urol 2006; 175: 1262–1267; discussion 1267.
22.
Chang SS, Hassan JM, Cookson MS, et al: Delaying radical cystectomy for muscle invasive bladder cancer results in worse pathological stage. J Urol 2003; 170: 1085–1087.
23.
Alva AS, Tallman CT, He C, et al: Efficient delivery of radical cystectomy after neoadjuvant chemotherapy for muscle-invasive bladder cancer: a multidisciplinary approach. Cancer 2012; 118: 44–53.
24.
Cognetti F, Ruggeri EM, Felici A, et al: Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol 2012; 23: 695–700.
25.
Malmström PU, Rintala E, Wahlqvist R, et al: Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: nordic cystectomy trial 1. The Nordic Cooperative Bladder Cancer Study Group. J Urol 1996; 155: 1903–1906.
26.
Weight CJ, Garcia JA, Hansel DE, et al: Lack of pathologic down-staging with neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder: a contemporary series. Cancer 2009; 115: 792–799.
27.
Yuh BE, Ruel N, Wilson TG, et al: Pooled analysis of clinical outcomes with neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer. J Urol 2013; 189: 1682–1686.
28.
Dash A, Pettus JA, Herr HW, et al: A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer 2008; 113: 2471–2477.
29.
Svatek RS, Shariat SF, Lasky RE, et al: The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder. Clin Cancer Res 2010; 16: 4461–4467.
30.
Sternberg CN, Skoneczna I, Kerst JM, et al: Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol 2015; 16: 76–86.
31.
De Santis M, Bellmunt J, Mead G, et al: Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/­carboplatin/vinblastine in patients with ­advanced urothelial cancer “unfit” for cisplatin-based chemotherapy: phase II – results of EORTC study 30986. J Clin Oncol 2009; 27: 5634–5639.
32.
Anan G, Hatakeyama S, Fujita N, et al: Trends in neoadjuvant chemotherapy use and oncological outcomes for muscle-invasive bladder cancer in Japan: a multicenter study. Oncotarget 2017; 8: 86130–86142.
33.
Apolo AB, Kim JW, Bochner BH, et al: Examining the management of muscle-invasive bladder cancer by medical oncologists in the United States. Urol Oncol 2014; 32: 637–644.
34.
Mathieu R, Lucca I, Rouprêt M, et al: The prognostic role of lymphovascular invasion in urothelial carcinoma of the bladder. Nat Rev Urol 2016; 13: 471–479.
© 2018 S. Karger AG, Basel
2018
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.