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Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols

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Abstract

Introduction

The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols.

Methods

A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan–Meier survival analysis was performed to detect Recurrence-free survival (RFS).

Results

Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66–79), and a median follow-up time of 18 months (IQR 9–25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences.

Conclusion

Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.

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Data availability

The data that support the findings of this study are available on a reasonable request from the corresponding author, and after compliance with ethical guidelines.

Abbreviations

BCG:

Bacillus Calmette-Guérin

AUA:

American Urological Association

Gem/Doce:

Gemcitabine/Docetaxel

TCC:

Transitional cell carcinoma

TURBT:

Transurethral resection of bladder tumor

TaLG:

Papillary low-grade TCC

TaHG:

Papillary high-grade TCC

TCC T1HG:

TCC invasive to lamina propria, high-grade

CIS:

Carcinoma in situ

FDA:

Food and drug administration

References

  1. Bladder Cancer—Cancer Stat Facts [Internet]. [cited 2023 Aug 23]. Available from: https://seer.cancer.gov/statfacts/html/urinb.html

  2. Deng S, Meng F, Wang L, Yang Z, Xuan L, Xuan Z et al (2022) Global research trends in non-muscle invasive bladder cancer: Bibliometric and visualized analysis. Front Oncol 12:1044830

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wan JCM (2020) Survival outcomes of early versus deferred cystectomy for non-muscle-invasive bladder cancer: a systematic review. Curr Urol 14(2):66–73. https://doi.org/10.1159/000499257

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR et al (2016) Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. https://doi.org/10.1016/j.juro.2016.06.049

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wroclawski ML, Schutz FA, Cha JD, Soares A (2019) Alternative therapies to bacillus calmette-guérin shortage for nonmuscle invasive bladder cancer in brazil and other underdeveloped countries: management considerations. J Glob Oncol 5:1–9

    PubMed  Google Scholar 

  6. Balasubramanian A, Gunjur A, Weickhardt A, Papa N, Bolton D, Lawrentschuk N et al (2022) Adjuvant therapies for non-muscle-invasive bladder cancer: advances during BCG shortage. World J Urol 40(5):1111–1124

    Article  PubMed  Google Scholar 

  7. Grimm MO, van der Heijden AG, Colombel M, Muilwijk T, Martínez-Piñeiro L, Babjuk MM et al (2020) Treatment of high-grade non-muscle-invasive bladder carcinoma by standard number and dose of BCG instillations versus reduced number and standard dose of BCG instillations: results of the european association of urology research foundation randomised pha. Eur Urol 78(5):690–698

    Article  PubMed  Google Scholar 

  8. Roumiguié M, Kamat AM, Bivalacqua TJ, Lerner SP, Kassouf W, Böhle A et al (2022) international bladder cancer group consensus statement on clinical trial design for patients with bacillus calmette-guérin-exposed high-risk non-muscle-invasive bladder cancer. Eur Urol 82(1):34–46

    Article  PubMed  Google Scholar 

  9. Steinberg RL, Thomas LJ, O’Donnell MA, Nepple KG (2015) Sequential intravesical gemcitabine and docetaxel for the salvage treatment of non-muscle invasive bladder cancer. Bl Cancer (Amsterdam, Netherlands) 1(1):65–72

    Google Scholar 

  10. McElree IM, Orzel J, Stubbee R, Steinberg RL, Mott SL, O’Donnell MA et al (2023) Sequential intravesical gemcitabine and docetaxel for treatment-naïve and previously treated intermediate-risk nonmuscle invasive bladder cancer. Urol Oncol. https://doi.org/10.1016/j.urolonc.2023.06.017

    Article  PubMed  Google Scholar 

  11. McElree IM, Steinberg RL, Martin AC, Richards J, Mott SL, Gellhaus PT et al (2022) Sequential intravesical gemcitabine and docetaxel for bacillus calmette-guérin-naïve high-risk nonmuscle-invasive bladder cancer. J Urol 208(3):589–599

    Article  PubMed  Google Scholar 

  12. Addeo R, Caraglia M, Bellini S, Abbruzzese A, Vincenzi B, Montella L et al (2010) Randomized phase III trial on gemcitabine versus mytomicin in recurrent superficial bladder cancer: evaluation of efficacy and tolerance. J Clin Oncol Off J Am Soc Clin Oncol 28(4):543–548

    Article  CAS  Google Scholar 

  13. Di Lorenzo G, Perdonà S, Damiano R, Faiella A, Cantiello F, Pignata S et al (2010) Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial. Cancer 116(8):1893–1900

    Article  PubMed  Google Scholar 

  14. Rezaee ME, Ismail AAO, Okorie CL, Seigne JD, Lynch KE, Schroeck FR (2021) Partial versus complete bacillus calmette-guérin intravesical therapy and bladder cancer outcomes in high-risk non-muscle-invasive bladder cancer: is NIMBUS the full story? Eur Urol open Sci 26:35–43

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mayor N, Fankhauser C, Sangar V, Mostafid H (2021) Management of NMIBC during BCG shortage and COVID-19. Trends Urol Men’s Health. 12:7–11

    Article  Google Scholar 

  16. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD et al (2009) The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 250(2):187–196

    Article  PubMed  Google Scholar 

  17. Sylvester RJ (2011) Bacillus Calmette-Guérin treatment of non-muscle invasive bladder cancer. Int J Urol Off J Japanese Urol Assoc 18(2):113–120

    CAS  Google Scholar 

  18. Kamat AM, Witjes JA, Brausi M, Soloway M, Lamm D, Persad R et al (2014) Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer. J Urol 192(2):305–315

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yim K, Melnick K, Mott SL, Carvalho FLF, Zafar A, Clinton TN et al (2023) Sequential intravesical gemcitabine/docetaxel provides a durable remission in recurrent high-risk NMIBC following BCG therapy. Urol Oncol. https://doi.org/10.1097/JU.0000000000002633.14

    Article  PubMed  Google Scholar 

  20. Koguchi D, Matsumoto K, Hirayama T, Moroo S, Kobayashi M, Katsumata H et al (2020) Impact of maintenance therapy using a half dose of the bacillus Calmette-Guérin Tokyo strain on recurrence of intermediate and high-risk nonmuscle invasive bladder cancer: a retrospective single-center study. BMC Urol 20(1):194

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sylvester RJ, Brausi MA, Kirkels WJ, Hoeltl W, Calais Da Silva F, Powell PH et al (2010) Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk. Eur Urol. 57(5):766–73

    Article  PubMed  Google Scholar 

  22. Lamm DL, Blumenstein BA, Crissman JD, Montie JE, Gottesman JE, Lowe BA et al (2000) Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol 163(4):1124–1129

    Article  CAS  PubMed  Google Scholar 

  23. McElree IM, Steinberg RL, Mott SL, O’Donnell MA, Packiam VT (2023) Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the treatment of patients with high-risk non-muscle-invasive bladder cancer. JAMA Netw open 6(2):e230849

    Article  PubMed  PubMed Central  Google Scholar 

  24. Shelley MD, Jones G, Cleves A, Wilt TJ, Mason MD, Kynaston HG (2012) Intravesical gemcitabine therapy for non-muscle invasive bladder cancer (NMIBC): a systematic review. BJU Int 109(4):496–505

    Article  CAS  PubMed  Google Scholar 

  25. Gontero P, Casetta G, Maso G, Sogni F, Pretti G, Zitella A et al (2004) Phase II study to investigate the ablative efficacy of intravesical administration of gemcitabine in intermediate-risk superficial bladder cancer (SBC). Eur Urol 46(3):339–343

    Article  CAS  PubMed  Google Scholar 

  26. Bartoletti R, Cai T, Gacci M, Giubilei G, Viggiani F, Santelli G et al (2005) Intravesical gemcitabine therapy for superficial transitional cell carcinoma: results of a Phase II prospective multicenter study. Urology 66(4):726–731

    Article  PubMed  Google Scholar 

  27. Gontero P, Cattel L, Paone TC, Milla P, Berta G, Fiorito C et al (2010) Pharmacokinetic study to optimize the intravesical administration of gemcitabine. BJU Int 106(11):1652–1656

    Article  CAS  PubMed  Google Scholar 

  28. Steinberg RL, Thomas LJ, Brooks N, Mott SL, Vitale A, Crump T et al (2020) Multi-institution evaluation of sequential gemcitabine and docetaxel as rescue therapy for nonmuscle invasive bladder cancer. J Urol 203(5):902–909

    Article  PubMed  Google Scholar 

  29. Tan WS, McElree IM, Davaro F, Steinberg RL, Bree K, Navai N et al (2023) Sequential intravesical gemcitabine and docetaxel is an alternative to Bacillus Calmette-Guérin for the treatment of intermediate-risk non-muscle-invasive bladder cancer. Eur Urol Oncol. https://doi.org/10.1016/j.euo.2023.06.011

    Article  PubMed  Google Scholar 

  30. Daniels MJ, Barry E, Milbar N, Schoenberg M, Bivalacqua TJ, Sankin A et al (2020) An evaluation of monthly maintenance therapy among patients receiving intravesical combination gemcitabine/docetaxel for nonmuscle-invasive bladder cancer. Urol Oncol 38(2):40.e17-40.e24

    Article  CAS  PubMed  Google Scholar 

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Funding

The authors received no financial support for this research.

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Author notes

  1. Reuben Ben-David and Neeraja Tillu have shared equal contribution.

Authors and Affiliations

  1. Department of Urology, Icahn School of Medicine at Mount Sinai, The Milton and Carroll Petrie, New York, NY, USA

    Reuben Ben-David, Neeraja Tillu, Christine Bieber, Daniel Ranti, Serena Tolani, Justin Eisenhauer, Etienne Lavallée, Nikhil Waingankar, Kyrollis Attalla, Peter Wiklund, Reza Mehrazin & John P. Sfakianos

  2. Department of Urology, Ichan School of Medicine at Mount Sinai, Tisch Cancer Institute, 1425 Madison Avenue, New York, NY, USA

    Reuben Ben-David, Neeraja Tillu, Parissa Alerasool, Nikhil Waingankar, Kyrollis Attalla, Peter Wiklund, Reza Mehrazin & John P. Sfakianos

  3. School of Medicine, New York Medical College, Valhalla, NY, USA

    Parissa Alerasool

  4. Department of Urology, Columbia University Irving Medical Center, New York, NY, USA

    Rainjade Chung & Christopher B. Anderson

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Contributions

N.T., R.BD, and JPS conceived the idea and study design, R.BD, N.T, J.E, C.B, D.R, S.T, JE, R.C, E.L and P. A collected the data, R.BD analyzed the data. R.BD, N.J and JPS led the manuscript writing; K.A., N.W., R.M., C.BA, and P.W. assisted with study design and provided consultation and guidance in manuscript writing. All authors have reviewed and approved this version of the manuscript.

Corresponding author

Correspondence to Reuben Ben-David.

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The authors declare no conflict of interest.

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The study protocol was approved by the local Ethics Committee (#23–01201), informed consent was waived.

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Ben-David, R., Tillu, N., Alerasool, P. et al. Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols. World J Urol 42, 315 (2024). https://doi.org/10.1007/s00345-024-04992-5

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