Radical treatment of muscle-invasive bladder cancer—are options equal?

  • David Fackrell
  • Andrea Marshall
  • Pankaj Mistry
  • Janet Dunn
  • Maria De Santis
  • Daniel Ford
  • Anjali Zarkar
Original Research
  • 8 Downloads

Abstract

Objective

To compare the modalities used to treat muscle-invasive bladder cancer (MIBC) and assess response to fractionated neoadjuvant chemotherapy.

Patients and methods

We retrospectively reviewed patients with MIBC that were treated with neoadjuvant fractionated gemcitabine–cisplatin (GC) and subsequently received radical treatment.

Disease-free interval and overall survival curves were constructed using the Kaplan–Meier method. A Cox proportional hazards model was used to obtain hazard ratios, confidence intervals and associated p value in a univariate analysis.

Results

A total of 122 patients were included, of which 21 (17%) patients were treated with radiotherapy (RT), 27 (22%) were given chemo-radiotherapy (CRT) and (61%) 74 had surgery only. Median follow-up is 4.8 years (range 0.7–11.8 years). Definitive treatment did not significantly affect overall survival (p = 0.16) or disease-free interval (p = 0.74). The 5 year overall survival rates were 44% for RT, 54% for CRT and 55% for surgery and 47, 49 and 58% respectively, for disease-free interval. Ninety-six percent of patients received at least three cycles of fractionated neoadjuvant GC. Twenty-six percent of patients achieved a pathological complete response post cystectomy and only two patients progressed during this treatment.

Conclusions

Patients with MIBC can potentially be treated with surgery, or with bladder preserving techniques—RT and CRT. No randomised evidence exists to directly compare radical options and a frequently used neoadjuvant chemotherapy regime also lacks randomised data. Patients responded well to and tolerated fractionated gemcitabine and cisplatin. This regime can be used in patients with an eGFR as low as 40 ml/min.

Our results support the use of chemo-radiotherapy or surgery as radical treatments in suitable patients with MIBC. All patients should be considered for and be given the option of both cystectomy and chemo-radiotherapy.

Keywords

Bladder cancer Cystectomy Radical Radiotherapy Neoadjuvant chemotherapy 

Notes

Compliance with ethical standards

Funding

No funding was received for this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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

Informed consent

For this type of study, formal consent is not required. /Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
  2. 2.
    Rodel C, Weiss C, Sauer R (2005) Organ preservation by combined modality treatment in bladder cancer: the European perspective. Semin Radiat Oncol 15(1):28–35CrossRefPubMedGoogle Scholar
  3. 3.
    Cookson MS (2005) The surgical management of muscle invasive bladder cancer: a contemporary review. Semin Radiat Oncol 15(1):10–18CrossRefPubMedGoogle Scholar
  4. 4.
    James ND, Hussain SA et al (2012) Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 366:1477–1488.  https://doi.org/10.1056/NEJMoa1106106 CrossRefPubMedGoogle Scholar
  5. 5.
    Stein JP, Lieskovsky G, Cote R et al (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1054 patients. J Clin Oncol 19(3):666–675CrossRefPubMedGoogle Scholar
  6. 6.
    Rodel C, Grabenbaer GG, Kuhn R et al (2002) Combined modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol 20(14):3061–3071CrossRefPubMedGoogle Scholar
  7. 7.
    Vashistha V, Wang H, Mazzone A, Liss MA, Svatek RS, Schleicher M, Kaushik D. (2017) Radical cystectomy compared to combined modality treatment for muscle-invasive bladder Cancer: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys 1;97(5):1002–1020Google Scholar
  8. 8.
    Paramasivan S, Huddart P, Hall E et al (2011) Key issues in recruitment to randomised controlled trials with very different interventions: a qualitative investigation of recruitment to the SPARE trial. Trials 12:78CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Sternberg CN (2005) Chemotherapy for local treatment of bladder cancer. Semin Radiat Oncol 15(1):60–65CrossRefPubMedGoogle Scholar
  10. 10.
    Advanced Bladder Cancer (ABC) (2003) Meta-analysis collaboration neoadjuvant chemotherapy in invasive bladder cancer - a systematic review and meta-analysis. Lancet 361:1927–1934CrossRefGoogle Scholar
  11. 11.
    Vale CL (2005) 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 48(2):202–206CrossRefGoogle Scholar
  12. 12.
    Hussain MHA, Wood DP et al (2009) Bladder cancer: narrowing the gap between evidence and practice. J Clin Oncol 27(34):5680–5684CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    International Collaboration of Trialists (1999) Neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy for muscle invasive bladder cancer: a randomised controlled trial. Lancet 354:533–540CrossRefGoogle Scholar
  14. 14.
    Von der Maase H et al (2000) 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 18(17):3068–3077CrossRefPubMedGoogle Scholar
  15. 15.
    Dash A et al (2008) A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder. Cancer 113(9):2471–2477CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Scosyrev E et al (2012) Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder. Cancer 118(1):72–81CrossRefPubMedGoogle Scholar
  17. 17.
  18. 18.
    HEFT Annual Report and Accounts 2016/17 http://www.heartofengland.nhs.uk/wp-content/uploads/HEFT-Annual-Report-2016-17.pdf]. (Accessed 3rd Sep 2017)
  19. 19.
    Isharwal S, Konety B (2015) Non-muscle invasive bladder cancer risk stratification. Indian J Urol 31(4):289–296CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Huddart RA, Hall M, Miranda M, Crundwell M, Jenkins P, Rawlings CL (2017) Quality of life (QL) of patients (pts) treated for muscle invasive bladder cancer (MIBC) with radiotherapy (RT) +/- chemotherapy (CT) in the BC2001 trial (CRUK/01/004): Analysis of impact of treatment at an individual level. J Clin Oncol 35 (suppl 6S; abstract) 292–292.  https://doi.org/10.1200/JCO.2017.35.6_suppl.292
  21. 21.
    Cowan RA, McBain CA, Ryder WDJ, Wylie JP, Logue JP, Turner SL, van der Voet J, Collins CD, Khoo VS, Read GR (2004) Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy. Int J Radiat Oncol Biol Phys 59(1):197–207CrossRefPubMedGoogle Scholar
  22. 22.
    Dutta SC, Chang SS, Coffey CS, Smith JA Jr, Jack G, Cookson MS (2002) Health related quality of life assessment after radical cystectomy: comparison of ileal conduit with continent orthotopic neobladder. J Urol 168(1):164–167CrossRefPubMedGoogle Scholar
  23. 23.
    Sternberg CN, Yagoda A, Scher HI, Watson RC, Geller N, Herr HW, Morse MJ, Sogani PC, Vaughan ED, Bander N, Weiselberg L, Rosado K, Smart T, Lin S-Y, Penenberg D, Fair WR, Whitmore WF (1989) Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse. Cancer 64(12):2448–2458CrossRefPubMedGoogle Scholar
  24. 24.
    Gandaglia G et al (2014) The effect of neoadjuvant chemotherapy on perioperative outcomes in patients who have bladder cancer treated with radical cystectomy: a population-based study. Eur Urol 66(3):561–568CrossRefPubMedGoogle Scholar
  25. 25.
    Chamie K, Hu B, Devere White RW, Ellison LM (2008) Cystectomy in the elderly: does the survival benefit in younger patients translate to the octogenarians? BJU Int 102:284–290CrossRefPubMedGoogle Scholar
  26. 26.
    Haresh KP, Julka PK, Sharma DN, Rath GK, Prabhakar R, Seth A (2007) A prospective study evaluating surgery and chemo radiation in muscle invasive bladder cancer. J Cancer Res Ther 3:81–85CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Heart of England Foundation TrustBirminghamUK
  2. 2.Queen Elizabeth HospitalBirminghamUK
  3. 3.Clinical Trials UnitUniversity of WarwickCoventryUK

Personalised recommendations