Advertisement

Peri-operative Chemotherapy for Muscle-Invasive Bladder Cancer

  • Thomas Seisen
  • Benjamin Pradère
  • Morgan RouprêtEmail author
Reference work entry

Abstract

The role of perioperative chemotherapy as an adjunct to radical cystectomy for muscle-invasive bladder cancer has been explored by several landmark randomized controlled trials over the past decades. On the one hand, a meta-analysis of level-I evidence and long-term results from the largest trials support the use of neoadjuvant chemotherapy, which is now advocated as the standard of care by most of the clinical guidelines worldwide. On the other hand, evidence supporting the use of adjuvant chemotherapy is more contentious. Specifically, several meta-analyses identified a survival benefit with the immediate postoperative delivery of cisplatin-based regimen, but the investigators identified multiple methodological limitations in the vast majority of included randomized controlled trials. Nonetheless, the use of adjuvant chemotherapy is currently considered for patients with adverse pathological features at radical cystectomy. The toxicity of both neoadjuvant and adjuvant chemotherapy is acceptable and well-aligned with what expected with cisplatin-based regimens. Given its greater response rate, the methotrexate, vinblastine, doxorubicine, and cisplatin combination is preferentially used in the neoadjuvant setting, while the gemcitabine plus cisplatin combination is more commonly delivered in the adjuvant setting because of its better toxicity profile. However, there is no prospective evidence suggesting a survival superiority of one regimen over the other. Finally, the comparative effectiveness of neoadjuvant vs. adjuvant chemotherapy has been poorly assessed in the current literature. Nonetheless, the only randomized controlled trial indirectly comparing both suggested no survival difference between the pre- and postoperative delivery of cisplatin-based chemotherapy.

Keywords

Urinary bladder neoplasms Cystectomy Drug therapy Neoadjuvant therapy Chemotherapy Adjuvant Cisplatin 

References

  1. Adjuvant chemotherapy for invasive bladder cancer (individual patient data). Advanced Bladder Cancer (ABC) Meta-analysis collaboration. Cochrane Database Syst Rev. 2006;(2):CD006018. Review.Google Scholar
  2. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet. 2003;361:1927–34.CrossRefGoogle Scholar
  3. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005;48(2):202–6.Google Scholar
  4. Alfred Witjes J, Lebret T, Compérat EM, Cowan NC, De Santis M, Bruins HM, Hernández V, Espinós EL, Dunn J, Rouanne M, Neuzillet Y, Veskimäe E, van der Heijden AG, Gakis G, Ribal MJ. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 2017;71(3):462–475.CrossRefGoogle Scholar
  5. Anon. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999;354:533–40.CrossRefGoogle Scholar
  6. Baras AS, Gandhi N, Munari E, et al. Identification and validation of protein biomarkers of response to neoadjuvant platinum chemotherapy in muscle invasive urothelial carcinoma. PLoS One. 2015;10:e0131245.CrossRefGoogle Scholar
  7. Bono AV, Benvenuti C, Gibba A, et al. Adjuvant chemotherapy in locally advanced bladder cancer. Final analysis of a controlled multicentre study. Acta Urologica Italica. 1997;11(1):5–8.Google Scholar
  8. Choueiri TK, Jacobus S, Bellmunt J, et al. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol. 2014;32:1889–94.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. Culp SH, Dickstein RJ, Grossman HB, et al. Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol. 2014;191:40–7.CrossRefGoogle Scholar
  11. Damrauer JS, Hoadley KA, Chism DD, et al. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A. 2014;111:3110–5.CrossRefGoogle Scholar
  12. 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;113:2471–7.CrossRefGoogle Scholar
  13. 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;178:451–4.CrossRefGoogle Scholar
  14. Duivenvoorden WC, Daneshmand S, Canter D, Lotan Y, Black PC, Abdi H, van Rhijn BW, Fransen van de Putte EE, Zareba P, Koskinen I, Kassouf W, Traboulsi SL, Kukreja JE, Boström PJ, Shayegan B, Pinthus JH. Incidence, characteristics and implications of thromboembolic events in patients with muscle invasive urothelial carcinoma of the bladder undergoing neoadjuvant chemotherapy. J Urol. 2016;196(6):1627–1633.CrossRefGoogle Scholar
  15. Fléchon A, Fizazi K, Gourgou-Bourgade S, et al. Gemcitabine and cisplatin after radical cystectomy for bladder cancer in an adjuvant setting: feasibility study from the Genito-urinary Group of the French Federation of cancer Centers. Anticancer. Drugs. 2006;17:705–8.Google Scholar
  16. Freiha F, Reese J, Torti FM. A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. J Urol. 1996;155:495–499–500.CrossRefGoogle Scholar
  17. Galsky MD, Stensland KD, Moshier E, Sfakianos JP, McBride RB, Tsao CK, Casey M, Boffetta P, Oh WK, Mazumdar M, Wisnivesky JP. Effectiveness of adjuvant chemotherapy for locally advanced bladder cancer. J Clin Oncol. 2016;34(8):825–32.CrossRefGoogle Scholar
  18. 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;349:859–66.CrossRefGoogle Scholar
  19. International Collaboration of Trialists, Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group), European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, Australian Bladder Cancer Study Group, National Cancer Institute of Canada Clinical Trials Group, Finnbladder, Norwegian Bladder Cancer Study Group, Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011;29(16):2171–7.Google Scholar
  20. Johnson DC, Nielsen ME, Matthews J, et al. Neoadjuvant chemotherapy for bladder cancer does not increase risk of perioperative morbidity. BJU Int. 2014;114:221–8.CrossRefGoogle Scholar
  21. Khaled HM, Shafik HE, Zabhloul MS, et al. Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive transitional and squamous cell carcinoma of the bladder: effect on survival and bladder preservation. Clin Genitourin Cancer. 2014;12:e233–40.CrossRefGoogle Scholar
  22. Kitamura H, Tsukamoto T, Shibata T, et al. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan clinical oncology group study JCOG0209. Ann Oncol. 2014;25:1192–8.CrossRefGoogle Scholar
  23. Lehmann J, Franzaring L, Thüroff J, et al. Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer. BJU Int. 2006;97:42–7.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. Logothetis CJ, Johnson DE, Chong C, et al. Adjuvant cyclophosphamide, doxorubicin, and cisplatin chemotherapy for bladder cancer: an update. J Clin Oncol. 1988;6:1590–6.CrossRefGoogle Scholar
  26. Mazeron R, Petit C, Rivin E, Limkin E, Dumas I, Maroun P, Annede P, Martinetti F, Seisen T, Lefkopoulos D, Chargari C, Haie-Meder C. 45 or 50 Gy, Which is the optimal radiotherapy pelvic dose in locally advanced cervical cancer in the perspective of reaching magnetic resonance image-guided adaptive brachytherapy planning aims? Clin Oncol (R Coll Radiol). 2016;28(3):171–7.CrossRefGoogle Scholar
  27. McConkey DJ, Choi W, Shen Y, et al. A prognostic gene expression signature in the molecular classification of chemotherapy-naïve urothelial cancer is predictive of clinical outcomes from neoadjuvant chemotherapy: a phase 2 trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with bevacizumab in urothelial cancer. Eur Urol. 2016;69:855–62.CrossRefGoogle Scholar
  28. Millikan R, Dinney C, Swanson D, et al. Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC. J Clin Oncol. 2001;19:4005–13.CrossRefGoogle Scholar
  29. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999;354(9178):533–40.Google Scholar
  30. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Eur Urol. 2005;48(2):202–6.Google Scholar
  31. Osman MA, Gabr AM, Elkady MS. Neoadjuvant chemotherapy versus cystectomy in management of stages II, and III urinary bladder cancer. Arch Ital Urol Androl Organo Uff Soc Ital Ecogr Urol E Nefrol. 2014;86:278–83.CrossRefGoogle Scholar
  32. Otto T, Goebell PJ, Rübben H. Perioperative chemotherapy in advanced bladder cancer – part II: adjuvant treatment. Onkologie. 2003;26:484–8.PubMedGoogle Scholar
  33. Paz-Ares LG, Solsona E, Esteban E, Saez A, Gonzalez-Larriba J, Anton M, Hevia A, de la Rosa F, Guillem V, Bellmunt J. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. J Clin Oncol. 2010;28:18s.CrossRefGoogle Scholar
  34. Petrelli F, Coinu A, Cabiddu M, et al. Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis. Eur Urol. 2014;65:350–7.CrossRefGoogle Scholar
  35. Plimack ER, Hoffman-Censits JH, Viterbo R, et al. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014;32:1895–901.CrossRefGoogle Scholar
  36. Plimack ER, Dunbrack RL, Brennan TA, et al. Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol. 2015;68:959–67.CrossRefGoogle Scholar
  37. 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;67:165–70.CrossRefGoogle Scholar
  38. Ruggeri EM, Giannarelli D, Bria E, et al. Adjuvant chemotherapy in muscle-invasive bladder carcinoma: a pooled analysis from phase III studies. Cancer. 2006;106:783–8.CrossRefGoogle Scholar
  39. Sjödahl G, Lauss M, Lövgren K, et al. A molecular taxonomy for urothelial carcinoma. Clin Cancer Res. 2012;18:3377–86.CrossRefGoogle Scholar
  40. Sherif A, Holmberg L, Rintala E, Mestad O, Nilsson J, Nilsson S, Malmström PU, Nordic Urothelial Cancer Group. Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies. Eur Urol. 2004;45(3):297–303.CrossRefGoogle Scholar
  41. Skinner DG, Daniels JR, Russell CA, et al. The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial. J Urol. 1991;145:459–464–467.CrossRefGoogle Scholar
  42. 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.CrossRefGoogle Scholar
  43. Stadler WM, Lerner SP, Groshen S, Stein JP, Shi SR, Raghavan D, Esrig D, Steinberg G, Wood D, Klotz L, Hall C, Skinner DG, Cote RJ. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol. 2011;29(25):3443–9.CrossRefGoogle Scholar
  44. Stöckle M, Meyenburg W, Wellek S, et al. Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study and further clinical experience. J Urol. 1995;153:47–52.CrossRefGoogle Scholar
  45. Studer UE, Bacchi M, Biedermann C, et al. Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial. J Urol. 1994;152:81–4.CrossRefGoogle Scholar
  46. 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;16:4461–7.CrossRefGoogle Scholar
  47. von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18:3068–77.CrossRefGoogle Scholar
  48. Winquist E, Kirchner TS, Segal R, et al. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol. 2004;171:561–9.CrossRefGoogle Scholar
  49. Wosnitzer MS, Hruby GW, Murphy AM, et al. A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer. Cancer. 2012;118:358–64.CrossRefGoogle Scholar
  50. Yafi FA, Aprikian AG, Chin JL, et al. Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy: a Canadian multicentre experience. BJU Int. 2011;108:539–45.CrossRefGoogle Scholar
  51. Yin M, Joshi M, Meijer RP, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis. Oncologist. 2016;21:708–15.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Thomas Seisen
    • 1
  • Benjamin Pradère
    • 2
  • Morgan Rouprêt
    • 1
    Email author
  1. 1.Department of Urology, Pitié Salpétrière Hospital, Assistance Publique des Hôpitaux de ParisUniversity Paris Sorbonne (for seisen and roupret)ParisFrance
  2. 2.Department of UrologyCHRU Tours, Faculté de Médecine François RabelaisToursFrance

Section editors and affiliations

  • Wolfgang Otto
    • 1
  • Shahrokh F. Shariat
    • 2
  1. 1.der Universität RegensburgOberarzt der Klinik für UrologieRegensburgGermany
  2. 2.Departement of UrologyWeill Cornell Medical CenterNew YorkUSA

Personalised recommendations