Skip to main content

Advertisement

SpringerLink
Log in

Trimodality Therapy for Muscle-Invasive Bladder Cancer: Recent Advances and Unanswered Questions

  • Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Bladder-sparing trimodality therapy (TMT) has become an accepted alternative to cystectomy for selected muscle invasive bladder cancer (MIBC) patients unfit for cystectomy or opting for bladder preservation. This review will summarize recent advances in TMT for MIBC.

Recent Findings

A growing body of literature has emerged which supports the use of TMT. However, its delivery is yet to be standardized. The role of chemotherapy and predictive biomarkers remain to be elucidated. Novel bladder-sparing approaches, drug combinations including immunotherapy and targeted therapies are under investigation in clinical trials, with the goal of ultimately enhancing survival and quality of life outcomes.

Summary

Recent advances in TMT have made bladder preservation possible for MIBC patients seeking an alternative local therapy to cystectomy. With careful patient selection, TMT offers comparable survival outcomes to cystectomy, and improved quality of life as patients are able to successfully retain their bladder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel RL, Miller KD. Cancer statistics. CA Cancer J Clin. 2019;69(1):7–34. https://doi.org/10.3322/caac.21551.

    Article  Google Scholar 

  2. Scosyrev E, Noyes K, Feng C, Messing E. Sex and racial differences in bladder cancer presentation and mortality in the US. Cancer. 2009;115:68–74. https://doi.org/10.1002/cncr.

    Article  CAS  PubMed  Google Scholar 

  3. Burger M, Catto JWF, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234–41. https://doi.org/10.1016/j.eururo.2012.07.033.

  4. Canadian Cancer Statistics Advisory Committee. Canadian Cancer Statistics. A 2018 Special Report On Cancer Incidenc by Stage. 2018. cancer.ca/Canadian-Cancer-Statistics.

  5. Abdollah F, Gandaglia G, Thuret R, et al. Incidence, survival and mortality rates of stage-specific bladder cancer in United States: a trend analysis. Cancer Epidemiol. 2013;37(3):219–25. https://doi.org/10.1016/j.canep.2013.02.002.

    Article  PubMed  Google Scholar 

  6. Mari A, Campi R, Tellini R, Gandaglia G, Albisinni S, Abufaraj M, et al. Patterns and predictors of recurrence after open radical cystectomy for bladder cancer : a comprehensive review of the literature. World J Urol. 2018;36(2):157–70. https://doi.org/10.1007/s00345-017-2115-4.

  7. •• Chang SS, Bochner BH, Chou R, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline. J Urol. 2017;198(3):552–9. AUA/ASCO/ASTRO/SUO guideline on current management of MIBC.

  8. •• Witjes JA, Bruins M, Compérat E, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Assoc Urol Guidel. 2018:978–9. https://uroweb.org/guideline/bladder-cancer-muscle. EAU guideline on current management of MIBC. Accessed 11 Aug 2019.

  9. •• Flaig TW, NCCN Bladder Cancer Panel. Bladder Cancer. NCCN Clin Pract Guidel Oncol. 2019;version 4. https://www.nccn.org/professionals/physician_gls/default.aspx. NCCN guideline on current management of MIBC. Accessed 11 Aug 2019.

  10. Haque W, Verma V, Aghazadeh M, Darcourt J, Butler E, Teh B. Short-term mortality associated with definitive chemoradiotherapy versus radical cystectomy for muscle-invasive bladder cancer. Clin Genitourin Cancer. 2019. https://doi.org/10.1016/j.clgc.2019.06.015.

  11. Djaladat H, Katebian B, Bazargani ST, Miranda G. 90-day complication rate in patients undergoing radical cystectomy with enhanced recovery protocol: a prospective cohort study. World J Urol. 2017;35:907–11. https://doi.org/10.1007/s00345-016-1950-z.

    Article  PubMed  Google Scholar 

  12. Johnson SC, Smith ZL, Golan S, Iii JFR, Smith ND, Steinberg GD. Temporal trends in perioperative morbidity for radical cystectomy using the National Surgical Quality Improvement Program database. Urol Oncol Semin Orig Investig. 2017;35(11):659.e13–9. https://doi.org/10.1016/j.urolonc.2017.07.013.

    Article  Google Scholar 

  13. Smith AB, Deal AM, Woods ME, Wallen EM, Pruthi RS, Chen RC, et al. Muscle-invasive bladder cancer: evaluating treatment and survival in the National Cancer Data Base. BJU Int. 2014;114(5):719–26. https://doi.org/10.1111/bju.12601.

  14. Westergren DO, Gårdmark T, Lindhagen L, Chau A, Malmström P. A nationwide population based analysis of patients with organ confined , muscle invasive bladder cancer not receiving curative intent therapy in Sweden from 1997 to 2014. J Urol. 2019. https://doi.org/10.1097/JU.0000000000000350.

  15. •• Kulkarni GS, Hermanns T, Wei Y, Bhindi B, Satkunasivam RAP, Sridhar SS. Propensity score analysis of radical cystectomy versus bladder-sparing trimodal therapy in the setting of a multidisciplinary bladder cancer clinic. J Clin Oncol. 2017;35(20):2299–307. https://doi.org/10.1200/JCO.2016.69.2327. The first propensity matching analysis comparing TMT vs RC showing TMT has similar long-term survival outcomes.

  16. Ploussard G, Daneshmand S, Efstathiou JA, Herr HW, James ND, Rödel CM, et al. Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review. Eur Urol. 2014;66(1):120–37. https://doi.org/10.1016/j.eururo.2014.02.038.

  17. Gakis G, Efstathiou J, Lerner S, Cookson M, Keegan K. ICUD-EAU international consultation on bladder cancer 2012: non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol. 2013;63(1):36–44. https://doi.org/10.1016/j.eururo.2012.08.061.

    Article  Google Scholar 

  18. Efstathiou JA, Spiegel DY, Shipley WU, Heney NM, Kaufman DS, Niemierko A, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol. 2012;61(4):705–11. https://doi.org/10.1016/j.eururo.2011.11.010.

  19. Buchser D, Zapatero A, Rogado J, et al. Long-term outcomes and patterns of failure following trimodality treatment with bladder preservation for invasive bladder cancer. Urology. 2019;124:183–90. https://doi.org/10.1016/j.urology.2018.07.058.

    Article  PubMed  Google Scholar 

  20. Perdona S, Autorino R, Damiano R, et al. Bladder-sparing, combined-modality approach for muscle-invasive bladder cancer. A multi-institutional, long-term experience. Cancer. 2008;112(1):75–83. https://doi.org/10.1002/cncr.23137.

    Article  PubMed  Google Scholar 

  21. Shipley WU, Winter KA, Kaufman DS, et al. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998;16(11):3576–83. https://doi.org/10.1200/jco.1998.16.11.3576.

    Article  CAS  PubMed  Google Scholar 

  22. Shipley WU, Kaufman DS, Zehr E, et al. Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer. Urology. 2002;60(1):62–7. https://doi.org/10.1016/S0090-4295(02)01650-3.

    Article  CAS  PubMed  Google Scholar 

  23. Weiner A, Desai A, Meeks J. Tumor location may predict adverse pathology and survival following definitive treatment for bladder cancer: a national cohort. Eur Urol Oncol. 2019;2(3):304–10. https://doi.org/10.1016/j.euo.2018.08.018.

    Article  PubMed  Google Scholar 

  24. Svatek RS, Clinton TN, Wilson CA, Kamat AM, Grossman HB, Dinney CP, et al. Intravesical tumor involvement of the trigone is associated with nodal metastasis in patients undergoing radical cystectomy. Urology. 2014;84(5):1147–51. https://doi.org/10.1016/j.urology.2014.05.011.

  25. Krasnow RE, Drumm M, Roberts HJ, et al. Clinical outcomes of patients with histologic variants of urothelial cancer treated with trimodality bladder-sparing therapy. Eur Urol. 2017;72(1):54–60. https://doi.org/10.1016/j.eururo.2016.12.002.

    Article  PubMed  Google Scholar 

  26. Bertz S, Wach S, Taubert H, Merten R, Krause FS, Schick S. Micropapillary morphology is an indicator of poor prognosis in patients with urothelial carcinoma treated with transurethral resection and radiochemotherapy. Virchows Arch. 2016;469:339–44. https://doi.org/10.1007/s00428-016-1986-x.

    Article  CAS  PubMed  Google Scholar 

  27. Johnson SB, Yu JB. Bladder preserving trimodality therapy for muscle-invasive bladder cancer. Curr Oncol Rep. 2018;20(9). https://doi.org/10.1007/s11912-018-0711-0.

  28. Kamat AM, Hahn NM, Efstathiou JA, et al. Bladder cancer. Lancet. 2016;388:2796–810. https://doi.org/10.1016/S0140-6736(16)30512-8.

    Article  PubMed  Google Scholar 

  29. • Zuiverloon TCM, van Kessel KEM, Bivalacqua TJ, et al. Recommendations for follow-up of muscle-invasive bladder cancer patients: a consensus by the international bladder cancer network. Urol Oncol. 2018. https://doi.org/10.1016/j.urolonc.2018.01.014. IBCN expert consensus guideline on surveillance post TMT and RC.

  30. Huddart RA, Birtle A, Maynard L, Beresford M, Blazeby J, Donovan J, et al. Clinical and patient-reported outcomes of SPARE – a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int. 2017;120:639–50. https://doi.org/10.1111/bju.13900.

  31. Gschwend E, Heck MM, Lehmann J, et al. Extended versus limited lymph node dissection in bladder cancer patients undergoing radical cystectomy: survival results from a prospective, Randomized Trial. Eur Urol. 2019;75:604–11. https://doi.org/10.1016/j.eururo.2018.09.047.

    Article  PubMed  Google Scholar 

  32. Culp S, Dickstein R, Grossman H, Pretzsch SM, Porten S, Daneshmand S, et al. Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol. 2014;191(1):40–7. https://doi.org/10.1016/j.juro.2013.07.061.Refining.

  33. Von Rundstedt F, Mata DA, Kryvenko ON, Shah AA. Utility of clinical risk stratification in the selection of muscle-invasive bladder cancer patients for neoadjuvant chemotherapy : a retrospective cohort study. Bladder Cancer. 2017;3:35–44. https://doi.org/10.3233/BLC-160062.

    Article  Google Scholar 

  34. • Fahmy O, Khairul-Asri MG, Schubert T, et al. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol Oncol Semin Orig Investig. 2018;36(2):43–53. https://doi.org/10.1016/j.urolonc.2017.10.002. The first meta-analysis comparing TMT vs RC accounting for effect of neoadjuvant chemotherapy.

  35. Vashistha V, Wang H, Mazzone A, et al. Radical cystectomy compared to combined modality treatment for muscle-invasive bladder Cancer: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys. 2017;97(5):1002–20. https://doi.org/10.1016/j.ijrobp.2016.11.056.

    Article  PubMed  Google Scholar 

  36. Zhong J, Switchenko J, Jegadeesh NK, Cassidy RJ, Gillespie TW, Master V, et al. Comparison of outcomes in patients with muscle-invasive bladder cancer treated with radical cystectomy versus bladder preservation. Am J Clin Oncol. 2019;42(1):36–41. https://doi.org/10.1097/COC.0000000000000471.

  37. Lin H, Krauss DJ, Ye H, Kernen KM, Hafron JM. National Cancer Database comparison of radical cystectomy vs chemoradiotherapy for muscle-invasive bladder cancer : implications of using clinical vs pathologic staging. Cancer Med. 2018;7:5370–81. https://doi.org/10.1002/cam4.1684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Giacalone NJ, Shipley WU, Clayman RH, et al. Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer: an updated analysis of the Massachusetts General Hospital experience. Eur Urol. 2017;71:952–60. https://doi.org/10.1016/j.eururo.2016.12.020.

    Article  PubMed  Google Scholar 

  39. Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, et al. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of radiation therapy oncology group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014;32(34):3801–9. https://doi.org/10.1200/JCO.2014.57.5548.

  40. Choudhury A, Swindell R, Logue JP, Elliott PA, Livsey JE, Wise M, et al. Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer. J Clin Oncol. 2011;29(6):733–8. https://doi.org/10.1200/JCO.2010.31.5721.

  41. Fischer-Valuck BW, Rudra S, Gabani P, et al. Impact of facility radiation patient volume on overall survival in patients with muscle invasive bladder cancer undergoing trimodality bladder preservation therapy. Bladder Cancer. 2019;Pre-press(Pre-press):1–10. https://doi.org/10.3233/BLC-190233.

    Article  Google Scholar 

  42. Mak KS, Smith AB, Eidelman A, et al. Quality of life in long-term survivors of muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2016;96(5):1028–36. https://doi.org/10.1016/j.ijrobp.2016.08.023.

    Article  PubMed  Google Scholar 

  43. Lagrange JL, Bascoul-Mollevi C, Geoffrois L, et al. Quality of life assessment after concurrent chemoradiation for invasive bladder cancer: results of a multicenter prospective study (getug 97-015). Int J Radiat Oncol Biol Phys. 2011;79(1):172–8. https://doi.org/10.1016/j.ijrobp.2009.10.038.

    Article  PubMed  Google Scholar 

  44. Zietman AL, Sacco D, Skowronski U, et al. Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of a urodynamic and quality of life study on long-term survivors. J Urol. 2003;170(5):1772–6. https://doi.org/10.1097/01.ju.0000093721.23249.c3.

    Article  PubMed  Google Scholar 

  45. Royce TJ, Feldman AS, Mossanen M, et al. Comparative effectiveness of bladder-preserving tri-modality therapy versus radical cystectomy for muscle-invasive bladder cancer. Clin Genitourin Cancer. 2018;17(1):23–31. https://doi.org/10.1016/j.clgc.2018.09.023.

    Article  PubMed  Google Scholar 

  46. Williams SB, Shan Y, Ray-zack MD, et al. Comparison of costs of radical cystectomy vs trimodal therapy for patients with localized muscle-invasive bladder cancer. JAMA Surg. 2019;154(8):1–9. https://doi.org/10.1001/jamasurg.2019.1629.

    Article  Google Scholar 

  47. Jichlinski P, Leisinger H. Fluorescence cystoscopy in the management of bladder cancer : a help for the urologist ! Urol Int. 2005;74:97–101. https://doi.org/10.1159/000083277.

    Article  PubMed  Google Scholar 

  48. Palou J, Hernandez C, Solsona E, et al. Effectiveness of hexaminolevulinate fl uorescence cystoscopy for the diagnosis of non-muscle- invasive bladder cancer in daily clinical practice: a Spanish multicentre observational study. BJU Int. 2015;116:37–43. https://doi.org/10.1111/bju.13020.

    Article  PubMed  Google Scholar 

  49. Burger M, Grossman HB, Droller M, Schmidbauer J, Hermann G, Drăgoescu O, et al. Photodynamic diagnosis of non – muscle-invasive bladder cancer with hexaminolevulinate cystoscopy : a meta-analysis of detection and recurrence based on raw data. Eur Urol. 2013;64:846–54. https://doi.org/10.1016/j.eururo.2013.03.059.

  50. Gakis G, Fahmy O. Systematic review and meta-analysis on the impact of hexaminolevulinate- versus white-light guided transurethral bladder tumor resection on progression in non-muscle invasive bladder cancer. Bladder Cancer. 2016;2(3):293–300. https://doi.org/10.3233/BLC-160060.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Daneshmand S, Patel S, Lotan Y, et al. Efficacy and safety of blue light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer : a phase III , comparative, multicenter study. J Urol. 2018;199:1158–65. https://doi.org/10.1016/j.juro.2017.11.096.

    Article  PubMed  Google Scholar 

  52. International collaboration of trialists. 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. https://doi.org/10.1200/JCO.2010.32.3139.

    Article  PubMed Central  Google Scholar 

  53. Advanced Bladder Cancer (ABC) Meta-Analysis Collaborators. Neoadjuvant chemotherapy in invasive bladder cancer : update of a systematic review and meta-analysis of individual patient data. Eur Urol. 2005;48:202–6. https://doi.org/10.1016/j.eururo.2005.04.006.

    Article  Google Scholar 

  54. 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(9):859–66. https://doi.org/10.1056/NEJMoa022148.

    Article  CAS  PubMed  Google Scholar 

  55. Jiang DM, Jiang H, Chung PWM, Zlotta AR, Fleshner NE, Bristow RG, et al. Neoadjuvant chemotherapy before bladder- sparing chemoradiotherapy in patients with nonmetastatic muscle-invasive bladder cancer. Clin Genitourin Cancer. 2019;17(1):38–45. https://doi.org/10.1016/j.clgc.2018.09.021.

  56. Hafeez S, Horwich A, Omar O, Mohammed K, Thompson A, Kumar P, et al. Selective organ preservation with neo-adjuvant chemotherapy for the treatment of muscle invasive transitional cell carcinoma of the bladder. Br J Cancer. 2015;112:1626–35. https://doi.org/10.1038/bjc.2015.109.

  57. Geynisman DM, Abbosh P, Zibelman M, et al. A phase II trial of risk enabled therapy after initiating neoadjuvant chemotherapy for bladder cancer (RETAIN BLADDER). J Clin Oncol. 2018;36:suppl 6S:abstr TPS537. Published February 26, 2018.

  58. Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ 3rd, Toonkel LM, et al. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology. 2009;73(4):833–7. https://doi.org/10.1016/j.urology.2008.09.036.

  59. Hagan MP, Winter KA, Kaufman DS, et al. RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys. 2003;57(3):665–72. https://doi.org/10.1016/S0360-3016(03)00718-1.

    Article  PubMed  Google Scholar 

  60. Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, et al. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013;14(9):863–72. https://doi.org/10.1016/S1470-2045(13)70255-9.

  61. James N, Hussain S, Hall E. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012:1477–88. https://doi.org/10.1016/j.eururo.2012.12.008.

  62. Goldsmith B, Baumann BC, He J, et al. Occult pelvic lymph node involvement in bladder cancer : implications for definitive radiation. Int J Radiat Oncol Biol Phys. 2014;88(3):603–10. https://doi.org/10.1016/j.ijrobp.2013.11.211.

    Article  PubMed  Google Scholar 

  63. Huddart RA, Hall E, Hussain SA, Jenkins P, Rawlings C, Tremlett J, et al. Randomized noninferiority trial of reduced high-dose volume versus standard volume radiation therapy for muscle-invasive bladder cancer: results of the BC2001 trial (CRUK/01/004). Int J Radiat Oncol Biol Phys. 2013;87(2):261–9. https://doi.org/10.1016/j.ijrobp.2013.06.2044.

  64. Tunio MA, Hashmi A, Qayyum A, Mohsin R, Zaeem A. Whole-pelvis or bladder-only chemoradiation for lymph node e negative invasive bladder cancer: single-institution experience. Int J Radiat Oncol Biol Phys. 2012;82(3):e457–62. https://doi.org/10.1016/j.ijrobp.2011.05.051.

    Article  PubMed  Google Scholar 

  65. Turker P, Bostrom PJ, Wroclawski ML, et al. Upstaging of urothelial cancer at the time of radical cystectomy : factors associated with upstaging and its effect on outcome. BJU Int. 2012;110:804–11. https://doi.org/10.1111/j.1464-410X.2012.10939.x.

    Article  PubMed  Google Scholar 

  66. Gray PJ, Lin CC, Jemal A, et al. Clinical-pathologic stage discrepancy in bladder cancer patients treated with radical cystectomy: results from the national cancer data base. Int J Radiat Oncol Biol Phys. 2014;88(5):1048–56. https://doi.org/10.1016/j.ijrobp.2014.01.001.

    Article  PubMed  Google Scholar 

  67. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual (7th ed). New York, NY: Springer; 2010.

  68. MB Amin, SB Edge, FL Greene, et al, editors. AJCC cancer staging manual (8th ed). New York: Springer; 2017.

  69. Tan MP, Harris V, Warren-oseni K, et al. The Intensity-Modulated Pelvic Node and Bladder Radiotherapy (IMPART) trial : a phase II single-centre prospective study. Clin Oncol. 2019. https://doi.org/10.1016/j.clon.2019.07.017.

  70. Kaufman D, Winter K, Shipley W, Heney NM, Chetner MP, Souhami L, et al. The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Oncologist. 2000;5:471–6.

    Article  CAS  Google Scholar 

  71. Mitin T, George A, Zietman AL, Heney NM, Kaufman DS, Uzzo RG, et al. Long-term outcomes among patients who achieve complete or near-complete responses after the induction phase of bladder-preserving combined-modality therapy for muscle- invasive bladder cancer: a pooled analysis of NRG oncology/ RTOG 9906 and 0233. Int J Radiat Oncol Biol Phys. 2016;94(1):67–74. https://doi.org/10.1016/j.ijrobp.2015.09.030.

  72. Horwich A, Dearnaley D, Huddart R, et al. Phase III randomised trial a randomised trial of accelerated radiotherapy for localised invasive bladder cancer. Radiother Oncol. 2005;75:34–43. https://doi.org/10.1016/j.radonc.2004.11.003.

    Article  PubMed  Google Scholar 

  73. Kwak Y, Lee S, Kay CS, Park HH. Intensity-modulated radiotherapy reduces gastrointestinal toxicity in pelvic radiation therapy with moderate dose. PLoS One. 2017;12(8):1–11.

    Google Scholar 

  74. Murthy V, Gupta P, Baruah K, Krishnatry R, Joshi A, Prabhash K, et al. Adaptive radiotherapy for carcinoma of the urinary bladder: long- term outcomes with dose escalation. Clin Oncol. 2019;31(9):646–52. https://doi.org/10.1016/j.clon.2019.06.005.

  75. Hafeez S, Warren-oseni K, Dcr T, et al. Prospective study delivering simultaneous integrated high-dose tumor boost (</=70 Gy) with image guided adaptive radiation therapy for radical treatment of localized muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2016;94(5):1022–30. https://doi.org/10.1016/j.ijrobp.2015.12.379.

    Article  PubMed  Google Scholar 

  76. Beulens AJW, Van Der Toorn P, De Wildt MJ, Scheepens WA. High-precision bladder cancer irradiation in the elderly : clinical results for a plan-of-the-day integrated boost technique with image guidance using Lipiodol markers. Eur Urol Oncol. 2018;2(1):39–46. https://doi.org/10.1016/j.euo.2018.08.012.

    Article  PubMed  Google Scholar 

  77. Coppin CM, Gospodarowicz MK, James K, Tannock IF, Zee B, Carson J, et al. Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1996;14(11):2901–7.

  78. Shipley WU, Prout GR, Einstein a B, et al. Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery. JAMA. 1987;258(7):931–5. https://doi.org/10.1001/jama.1987.03400070069037.

    Article  CAS  PubMed  Google Scholar 

  79. Dunst J, Sauer R, Schrott K, Kühn R, Wittekind C, Altendorf-Hofmann A. Organ-sparing treatment of advanced bladder cancer: a 10-year experience. Int J Radiat Oncol Biol Phys. 1994;30(2):261–6.

    Article  CAS  Google Scholar 

  80. Rose TL, Deal AM, Ladoire S, Créhange G, Galsky MD, Rosenberg JE, et al. Patterns of bladder preservation therapy utilization for muscle-invasive bladder cancer. Bladder Cancer. 2016;2(4):405–13. https://doi.org/10.3233/BLC-160072.

  81. Caffo O, Thompson C, De Santis M, et al. Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive bladder cancer : a pooled individual data analysis of eight phase I – II trials. Radiother Oncol. 2016;121(2):193–8. https://doi.org/10.1016/j.radonc.2016.09.006.

    Article  CAS  PubMed  Google Scholar 

  82. Coen JJ, Zhang P, Saylor PJ, Lee CT, Wu C, Parker W. Bladder preservation with twice-a-day radiation plus fluorouracil / cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder Cancer : NRG / RTOG 0712 — a randomized phase II trial. J Clin Oncol. 2019;37(1):44–51. https://doi.org/10.1200/JCO.18.00537.

    Article  CAS  PubMed  Google Scholar 

  83. Thompson C, Joseph N, Sanderson B, et al. Tolerability of concurrent chemoradiation therapy With gemcitabine ( GemX ), with and without prior neoadjuvant chemotherapy , in muscle invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2017;97(4):732–9. https://doi.org/10.1016/j.ijrobp.2016.11.040.

    Article  PubMed  Google Scholar 

  84. Krüger S, Weitsch G, Büttner H, Matthiensen A, Böhmer T, Marquardt T, et al. HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications. Int J Cancer. 2002;102:514–8. https://doi.org/10.1002/ijc.10731.

  85. Jimenez RE, Hussain M, Bianco FJ, et al. Her-2 /neu overexpression in muscle-invasive urothelial carcinoma of the bladder : prognostic significance and comparative analysis in primary and metastatic tumors 1. Clin Cancer Res. 2001;7(8):2440–7.

    CAS  PubMed  Google Scholar 

  86. Chakravarti A, Winter K, Wu C, et al. Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemot. Int J Radiat Oncol Biol Phys. 2005;62(2):309–17. https://doi.org/10.1016/j.ijrobp.2004.09.047.

    Article  CAS  PubMed  Google Scholar 

  87. • Michaelson MD, Hu C, Pham HT, et al. A phase 1 / 2 trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation after transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer ( Trial NRG Oncology RTOG 052). Int J Radiat Oncol Biol Phys. 2016;97(5):995–1001. https://doi.org/10.1016/j.ijrobp.2016.12.018. The first trial evaluating targeted therapy in TMT.

  88. Van De Putte EEF, Pos F, Doodeman B, et al. Concurrent radiotherapy and panitumumab after lymph node dissection and induction chemotherapy for invasive bladder cancer abstract purpose : materials and methods : results : conclusions. J Urol. 2019;201(3):478–85.

    Article  Google Scholar 

  89. Yang L, Taylor J, Eustace A, Irlam JJ, Denley H, Hoskin PJ, et al. A gene signature for selecting benefit from hypoxia modification of radiotherapy for high-risk bladder cancer patients. Clin Cancer Res. 2017;23(16):4761–8. https://doi.org/10.1158/1078-0432.CCR-17-0038.

  90. Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI. Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. J Clin Oncol. 2010;28(33):4912–8. https://doi.org/10.1200/JCO.2010.28.4950.

    Article  PubMed  Google Scholar 

  91. Azuma H, Inamoto T, Takahara K, Ibuki N, Nomi H, Komura K, et al. Tetramodal therapy using balloon-occluded arterial infusion of anticancer agents , the Azuma regimen , for lymph node-involved bladder cancer. Int J Oncol. 2019;54(1):167–76. https://doi.org/10.3892/ijo.2018.4619.

  92. Merten R, Ott O, Haderlein M, et al. Long-term experience of chemoradiotherapy combined with deep regional hyperthermia for organ preservation in high-risk bladder cancer ( Ta , Tis , T1 , T2 ). Oncologist. 2019;24:1–10. https://doi.org/10.1634/theoncologist.2018-0280.

    Article  CAS  Google Scholar 

  93. Sharabi AB, Nirschl CJ, Kochel CM, et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res. 2015;3(4):345–55. https://doi.org/10.1158/2326-6066.CIR-14-0196.

    Article  CAS  PubMed  Google Scholar 

  94. Rompré-brodeur A, Shinde-jadhav S, Ayoub M, et al. PD-1 / PD-L1 immune-checkpoint inhibition with radiation in bladder cancer : in situ and abscopal effects. Mol Cancer Ther. 2019. https://doi.org/10.1158/1535-7163.MCT-18-0986.

  95. Kijima T, Tanaka H, Koga F, Masuda H. Selective tetramodal bladder-preservation therapy , incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle-invasive bladder cancer : oncological and functional outcomes of 107 patients. BJU Int. 2019;124:242–50. https://doi.org/10.1111/bju.14736.

    Article  PubMed  Google Scholar 

  96. Choudhury A, Nelson LD, Teo MTW, Chilka S, Bhattarai S, Johnston CF, et al. MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res. 2010;70(18):7017–26. https://doi.org/10.1158/0008-5472.CAN-10-1202.

  97. Laurberg JR, Brems-eskildsen AS, Nordentoft I, et al. Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int. 2012:E1228–36. https://doi.org/10.1111/j.1464-410X.2012.11564.x.

  98. Meng W, Efstathiou J, Singh R, et al. MicroRNA biomarkers for patients with muscle- invasive bladder cancer undergoing selective bladder-sparing trimodality treatment. Int J Radiat Oncol Biol Phys. 2019;104(1):197–206. https://doi.org/10.1016/j.ijrobp.2018.12.028.

    Article  CAS  PubMed  Google Scholar 

  99. Tanaka H, Yoshida S. Impact of immunohistochemistry-based subtypes in muscle-invasive bladder cancer on response to chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2018;102(5):1408–16. https://doi.org/10.1016/j.ijrobp.2018.06.030.

    Article  CAS  PubMed  Google Scholar 

  100. Efstathiou JA, Mouw KW, Gibb EA, Liu Y, Wu CL, Drumm MR, et al. Impact of immune and stromal infiltration on outcomes following bladder-sparing trimodality therapy for muscle-invasive bladder cancer. Eur Urol. 2019;76(1):59–68. https://doi.org/10.1016/j.eururo.2019.01.011.

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Canada, 700 University Avenue, Toronto, ON, Canada

    Di Maria Jiang

  2. Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, University of Toronto, Canada, 700 University Ave, Toronto, ON, Canada

    Peter Chung

  3. Departments of Surgery and Surgical Oncology, Division of Urology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Canada, 6-824, 700 University Avenue, Toronto, ON, Canada

    Girish S. Kulkarni

  4. Department of Medicine, Division of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Canada, 700 University Avenue, Toronto, ON, Canada

    Srikala S. Sridhar

Authors
  1. Di Maria Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Girish S. Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Srikala S. Sridhar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Srikala S. Sridhar.

Ethics declarations

Conflict of Interest

Di Maria Jiang declares that she has no conflict of interest.

Peter Chung has received research funding from Sanofi, and has received honoraria from AbbVie and AstraZeneca.

Girish S. Kulkarni has served as an investigator on trials funded by Merck, AstraZeneca, Bristol-Myers Squibb, AbbVie, Theralase Technologies, and Sesen Bio; and has served on advisory boards for Ferring, Janssen, Bayer, Astellas, Merck, Roche, and Theralase Technologies.

Srikala S. Sridhar has received compensation from Roche, Merck, Pfizer, Bayer, BMS, Astellas and AstraZeneca for service as a consultant, and has received research funding from Janssen and Sanofi.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Genitourinary Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, D.M., Chung, P., Kulkarni, G.S. et al. Trimodality Therapy for Muscle-Invasive Bladder Cancer: Recent Advances and Unanswered Questions. Curr Oncol Rep 22, 14 (2020). https://doi.org/10.1007/s11912-020-0880-5

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-020-0880-5

Keywords

Search

Navigation