Intra-arterial chemotherapy combined with intravesical chemotherapy compared with intravesical BCG immunotherapy retrospectively in high-risk non-muscle-invasive bladder cancer after transurethral resection of the bladder tumor

Abstract

Objective

To compare the efficacy and safety of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IVC) against intravesical BCG immunotherapy in high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of the bladder tumor (TURBT).

Materials and methods

130 patients with high-risk NMIBC who had underwent TURBT were divided into two groups, of which IAC + IVC group received four courses of IAC (cisplatin and epirubicin) combined with IVC (epirubicin or pirarubicin) after surgery and BCG group received intravesical BCG immunotherapy. Recurrence rate and progression rate were assessed by Chi-square test, while recurrence-free survival and progression-free survival were calculated using the Kaplan–Meier method.

Results

In this study, the recurrence rate was 27.9% (12/43) in IAC + IVC group and 26.4% (14/53) in BCG group, while progression rate was 9.3% (4/43) in IAC + IVC group and 9.4% (5/53) in BCG group. Both of the recurrence and progression rate did not show a significant difference. In the Kaplan–Meier plot, no difference was found with respect to recurrence-free survival and progression-free survival. Moreover, 46.5% (20/43) patients suffered from adverse events of IAC and 83.1% (49/59) patients suffered from adverse events associated with BCG, of which 6 patients discontinued treatment due to serious adverse events of BCG. Univariate analysis suggested that only recurrent tumor could be an independent risk factor related to recurrence.

Conclusions

IAC combined with IVC used in high-risk NMIBC could reduce the recurrence and progression as effective as BCG instillation with lower adverse events.

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

Fig. 1
Fig. 2
Fig. 3

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Babjuk M et al (2019) (2019) European Association of Urology Guidelines on non-muscle-invasive bladder cancer (TaT1 and Carcinoma In Situ)—Update. Eur Urol 76:639–657. https://doi.org/10.1016/j.eururo.2019.08.016

    CAS  Article  PubMed  Google Scholar 

  2. Bohle A, Jocham D, Bock PR (2003) Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer: a formal meta-analysis of comparative studies on recurrence and toxicity. J Urol 169:90–95. https://doi.org/10.1097/01.ju.0000039680.90768.b3

    CAS  Article  PubMed  Google Scholar 

  3. Brausi M et al (2014) Side effects of Bacillus Calmette-Guerin (BCG) in the treatment of intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance. Eur Urol 65:69–76. https://doi.org/10.1016/j.eururo.2013.07.021

    CAS  Article  PubMed  Google Scholar 

  4. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Burger M et al (2013) Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 63:234–241. https://doi.org/10.1016/j.eururo.2012.07.033

    Article  PubMed  Google Scholar 

  6. Chen J, Yao Z, Qiu S, Chen L, Wang Y, Yang J, Li J (2013) Comparing intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone: a randomised prospective pilot study for T1G3 bladder transitional cell carcinoma after bladder-preserving surgery. Cardiovasc Intervent Radiol 36:1521–1526. https://doi.org/10.1007/s00270-013-0594-2

    Article  PubMed  Google Scholar 

  7. De Berardinis E, Busetto GM, Antonini G, Giovannone R, Gentile V (2011) T1G3 high-risk NMIBC (non-muscle invasive bladder cancer): conservative treatment versus immediate cystectomy. Int Urol Nephrol 43:1047–1057. https://doi.org/10.1007/s11255-011-9941-x

    Article  PubMed  Google Scholar 

  8. Eapen L, Stewart D, Collins J, Peterson R (2004) Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer. J Urol 172:1276–1280. https://doi.org/10.1097/01.ju.0000140456.42509.b6

    CAS  Article  PubMed  Google Scholar 

  9. Han B et al (2014) Organ preservation for muscle-invasive bladder cancer by preoperative intra-arterial chemotherapy and transurethral resection. Med Oncol 31:912. https://doi.org/10.1007/s12032-014-0912-9

    CAS  Article  PubMed  Google Scholar 

  10. Hoshi S, Mao H, Takahashi T, Suzuki K, Nose M, Orikasa S (1997) Internal iliac arterial infusion chemotherapy for rabbit invasive bladder cancer. Int J Urol 4:493–499. https://doi.org/10.1111/j.1442-2042.1997.tb00292.x

    CAS  Article  PubMed  Google Scholar 

  11. Huang B et al (2019) Evaluation of the effects of intra-arterial chemotherapy combined with intravesical chemotherapy against intravesical chemotherapy alone after transurethral resection of bladder tumor in T1-staged Grade 3 bladder cancer. J Cancer Res Clin Oncol 145:487–494. https://doi.org/10.1007/s00432-018-2811-5

    CAS  Article  PubMed  Google Scholar 

  12. Huang B, Zheng J, Yao Z, Fan W, Qiu S, Chen L, Chen J (2019) Efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy in T1G3 bladder cancer when compared with intravesical chemotherapy alone after bladder-sparing surgery: a retrospective study. World J Urol 37:823–829. https://doi.org/10.1007/s00345-018-2437-x

    CAS  Article  PubMed  Google Scholar 

  13. Kubota Y, Kakizaki H, Numasawa K, Suzuki K, Kato H (1989) Preoperative intra-arterial infusion chemotherapy for patients with bladder cancer. Eur Urol 16:189–194. https://doi.org/10.1159/000471567

    CAS  Article  PubMed  Google Scholar 

  14. Lian F et al (2019) Intra-arterial chemotherapy combined with intravesical chemotherapy is effective in preventing recurrence in non-muscle invasive bladder cancer. J Cancer Res Clin Oncol 145:1625–1633. https://doi.org/10.1007/s00432-019-02900-8

    Article  PubMed  Google Scholar 

  15. Miyanaga N et al (2000) A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer: a prospective study. Int J Urol 7:41–48. https://doi.org/10.1046/j.1442-2042.2000.00137.x

    CAS  Article  PubMed  Google Scholar 

  16. Miyata Y et al (2015) Efficacy and safety of systemic chemotherapy and intra-arterial chemotherapy with/without radiotherapy for bladder preservation or as neo-adjuvant therapy in patients with muscle-invasive bladder cancer: a single-centre study of 163 patients. Eur J Surg Oncol 41:361–367. https://doi.org/10.1016/j.ejso.2014.07.043

    CAS  Article  PubMed  Google Scholar 

  17. Oddens J et al (2013) Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol 63:462–472. https://doi.org/10.1016/j.eururo.2012.10.039

    Article  PubMed  Google Scholar 

  18. Packiam VT, Werntz RP, Steinberg GD (2019) Current clinical trials in non-muscle-invasive bladder cancer: heightened need in an era of chronic BCG shortage. Curr Urol Rep 20:84. https://doi.org/10.1007/s11934-019-0952-y

    Article  PubMed  Google Scholar 

  19. Sternberg IA, Keren Paz GE, Chen LY, Herr HW, Dalbagni G (2013) Role of immediate radical cystectomy in the treatment of patients with residual T1 bladder cancer on restaging transurethral resection. BJU Int 112:54–59. https://doi.org/10.1111/j.1464-410X.2012.11391.x

    Article  PubMed  Google Scholar 

  20. Sylvester RJ, van der Meijden AP, Lamm DL (2002) Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 168:1964–1970. https://doi.org/10.1097/01.ju.0000034450.80198.1c

    CAS  Article  PubMed  Google Scholar 

  21. Sylvester RJ et al (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49:466–465. https://doi.org/10.1016/j.eururo.2005.12.031 (discussion 475-467)

    Article  PubMed  Google Scholar 

  22. Thalmann GN, Markwalder R, Shahin O, Burkhard FC, Hochreiter WW, Studer UE (2004) Primary T1G3 bladder cancer: organ preserving approach or immediate cystectomy? J Urol 172:70–75. https://doi.org/10.1097/01.ju.0000132129.87598.3b

    Article  PubMed  Google Scholar 

  23. van der Meijden AP, Sylvester RJ, Oosterlinck W, Hoeltl W, Bono AV, Group EG-UTC (2003) Maintenance Bacillus Calmette-Guerin for Ta T1 bladder tumors is not associated with increased toxicity: results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial. Eur Urol 44:429–434. https://doi.org/10.1016/s0302-2838(03)00357-9

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by grants from the National Natural Science Foundation of China (No.81402116, No.82072817) and Natural Science Foundation of Guangdong Province, China (No. 2019A1515010285).

Author information

Affiliations

Authors

Contributions

LC, JC and XM contributed to the study conception, design and review. Data collection was performed by GH, XM and WL. Analysis was performed by GH and BH. The first draft of the manuscript was written by BH, and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lingwu Chen or Xiaopeng Mao or Junxing Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huang, B., Huang, G., Li, W. et al. Intra-arterial chemotherapy combined with intravesical chemotherapy compared with intravesical BCG immunotherapy retrospectively in high-risk non-muscle-invasive bladder cancer after transurethral resection of the bladder tumor. J Cancer Res Clin Oncol (2020). https://doi.org/10.1007/s00432-020-03453-x

Download citation

Keywords

  • Intra-arterial chemotherapy
  • Intravesical chemotherapy
  • BCG
  • High-risk non-muscle-invasive bladder cancer