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Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation

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Abstract

Purpose

Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC.

Methods

Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266.

Results

Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence.

Conclusions

Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

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Authors and Affiliations

  1. Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama, Okayama, 700-8558, Japan

    Ryuta Tanimoto, Yasuyuki Kobayashi, Yasutomo Nasu & Hiromi Kumon

  2. Department of Urology, Hiroshima City Hospital, Hiroshima, Hiroshima, Japan

    Takashi Saika & Shin Ebara

  3. Department of Urology, Kochi Health Science Center, Kochi, Kochi, Japan

    Ryoji Nasu

  4. Department of Urology, Mitoyo General Hospital, Kanonji, Kagawa, Japan

    Daisuke Yamada

  5. Department of Urology, Kurashiki Medical Center, Kurashiki, Okayama, Japan

    Hitoshi Takamoto

  6. Department of Urology, Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan

    Yoshiyuki Miyaji

  7. Department of Urology, Okayama Medical Center, Oskayama, Okayama, Japan

    Tomoyasu Tsushima

  8. Okayama Urological Research Group (OURG), Okayama, Okayama, Japan

    Takashi Saika, Shin Ebara, Yasuyuki Kobayashi, Ryoji Nasu, Daisuke Yamada, Hitoshi Takamoto, Yoshiyuki Miyaji, Yasutomo Nasu, Tomoyasu Tsushima & Hiromi Kumon

Authors
  1. Ryuta Tanimoto
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  2. Takashi Saika
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  3. Shin Ebara
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  7. Hitoshi Takamoto
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Contributions

RT: Data analysis, Manuscript writing/editing; TS: Protocol/project development, Data collection or management; SE: Protocol/project development, Data collection or management; YK: Protocol/project development, Data collection or management; RN: Protocol/project development, Data collection or management; DY: Protocol/project development, Data collection or management; HT: Protocol/project development, Data collection or management; YM: Protocol/project development, Data collection or management; YN: Protocol/project development, Data collection or management; TT: Protocol/project development, Data collection or management, Manuscript editing; HK: Protocol/project development, Data collection or management, Manuscript editing.

Corresponding author

Correspondence to Ryuta Tanimoto.

Ethics declarations

Conflict of interest

All authors of this manuscript declare no conflict of interest.

Ethical approval

The OURG (Okayama, Japan) has been funded by several companies, including Meiji Seika Pharma Co., Ltd. This research was performed using self-funding from the OURG (Okayama, Japan), which is a non-profit organization that promotes and conducts clinical research.

Research involving human participants and/or animals

This study was registered as UMIN C000000266 and approved by our institutional review board (IRB #05-1001).

Informed consent

Written informed consent was obtained from each patient based on local institutional guidelines.

Electronic supplementary material

Below is the link to the electronic supplementary material.

345_2018_2196_MOESM1_ESM.tif

Supplementary material 1 (TIFF 9494 kb) Supplementary Fig. 1. Kaplan–Meier curves of recurrence free survival for patients excluding high risk group. (Group A; a black broken line, Group B; a gray solid line), recurrence free survival rates and numbers at risk in each group

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Cite this article

Tanimoto, R., Saika, T., Ebara, S. et al. Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation. World J Urol 36, 889–895 (2018). https://doi.org/10.1007/s00345-018-2196-8

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  • DOI: https://doi.org/10.1007/s00345-018-2196-8

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