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Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer outcomes in patients without radical cystectomy

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Abstract

Background

Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) is a newly defined subtype that is unlikely to benefit from BCG rechallenge. Radical cystectomy is currently recommended for BCG-unresponsive NMIBC; however, a certain proportion of these patients can be managed with treatments other than that. Herein, we conducted a multicenter retrospective study to analyze the clinical outcomes of BCG-unresponsive NMIBC patients who did not receive radical cystectomy.

Methods

Of the 141 BCG-unresponsive NMIBC patients, 94 (66.7%) received treatment except radical cystectomy. Survival outcomes were calculated from the date of diagnosis using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were identified using the multivariate Cox regression model. This group was further classified into three groups according to the number of risk factors, and survival outcomes were compared.

Results

Multivariate analyses identified low estimated glomerular filtration rate (< 45 ml/min/1.73 m2) and large tumor size (≥ 30 mm) before BCG induction as independent poor prognostic factors for progression-free survival and overall survival, while the latter was also an independent factor for cancer-specific survival. The presence of variant histology was an independent poor prognostic factor for overall survival. The high-risk non-cystectomy group showed a significantly poor prognosis for progression-free survival (hazard ratio: 7.61, 95% confidence interval: 2.11–27.5), cancer-specific survival (10.4, 0.54–70.02), and overall survival (8.28, 1.82–37.7).

Conclusions

Our findings suggest that patients with renal impairment and large tumors should undergo radical cystectomy if the complications and intentions of the patients allow so.

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Abbreviations

BCG:

Bacillus Calmette-Guérin

BP:

Bladder prevention

CIS:

Cancer in situ

CKD-EPI:

Chronic Kidney Disease Epidemiology Collaboration

CSS:

Cancer-specific survival

ECOG-PS:

Eastern Cooperative Oncology Group-performance status

eGFR:

Estimated glomerular filtration rate

iBCG:

Bacillus Calmette-Guérin induction

JUA:

Japanese Urological Association

LVI:

Lymphovascular invasion

NIMBC:

Non-muscle invasive bladder cancer

OS:

Overall survival

PFS:

Progression-free survival

RC:

Radical cystectomy

TURBT:

Transurethral resection of bladder tumor

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Acknowledgements

The clinicopathological statistics are based on the results of contributions from a number of institutions in Japan. We thank the contributions of many urologists.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Kota Iida, Makito Miyake & Kiyohide Fujimoto

  2. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Kaoru Murakami & Takashi Kobayashi

  3. Department of Urology, National Cancer Center Hospital, Tokyo, Japan

    Motokiyo Komiyama

  4. Department of Urology, Nara City Hospital, Nara, Japan

    Eijiro Okajima

  5. Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan

    Tomokazu Sazuka

  6. Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan

    Naotaka Nishiyama & Hiroshi Kitamura

  7. Department of Urology, Shimane University, Izumo, Japan

    Hiroaki Yasumoto

  8. Department of Urology, Jikei University School of Medicine, Tokyo, Japan

    Takahiro Kimura

  9. Department of Urology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi, Japan

    Akihiro Ito

  10. Department of Urology, Harasanshin Hospital, Fukuoka, Japan

    Kenichiro Shiga

  11. Department of Urology, Faculty of Medicine, Yamagata University, Yamagata, Japan

    Atsushi Yamagishi

  12. Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan

    Hiroshi Kikuchi

  13. Department of Urology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa, Japan

    Mikio Sugimoto & Rikiya Taoka

  14. Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Takahiro Kojima & Hiroyuki Nishiyama

Authors
  1. Kota Iida
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  2. Makito Miyake
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  3. Kaoru Murakami
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  5. Eijiro Okajima
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  18. Hiroshi Kitamura
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  20. Kiyohide Fujimoto
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Corresponding author

Correspondence to Makito Miyake.

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Supplementary Information

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10147_2021_1988_MOESM1_ESM.tif

Supplementary file1 Supplementary Table 1. Comparison of background in patients with BCG-unresponsive NMIBC between the RC group and the non-RC group. Among the 141 patients with BCG-unresponsive NMIBC, 22 of the 73 in patients with high grade T1 at 3 months after initial BCG (30.1%), 17 of the 48 in patients with persistent high-grade NMIBC at 6 months despite adequate BCG (35.4%), and 8 of the 20 in patients with early relapsing (40.0%) underwent RC. Abbreviations: BCG, Bacillus Calmette-Guérin; NMIBC, non-muscle invasive bladder cancer; RC, radical cystectomy (TIF 572 KB)

10147_2021_1988_MOESM2_ESM.tif

Supplementary file2 Supplementary Table 2. Outcome of the non-radical cystectomy group. Of the patients undergoing TURBT alone, TURBT and BCG rechallenge and TURBT and maintenance intravesical chemotherapy, 13 (31.0%), 23 (51.1%), 5 (71.4%) did not experience progression. Abbreviations: TURBT, Transurethral resection of bladder tumor; BCG, Bacillus Calmette-Guérin (TIF 655 KB)

10147_2021_1988_MOESM3_ESM.tif

Supplementary file3 Supplementary Table 3. Univariate analyses for PFS, CSS and OS of the non-radical cystectomy group. The log-rank test showed that large tumor size and the presence of LVI before induction BCG were poor prognostic factors for PFS. Moreover, large tumor size (≥ 3 cm) before induction BCG was a poor prognostic factor for CSS, and low eGFR, large tumor size, and presence of variant histology before induction BCG were associated with OS. Abbreviations: PFS, Progression-free survival; CSS, cancer-specific survival; OS, Overall survival; LVI, Lymphovascular invasion; BCG, Bacillus Calmette-Guérin; eGFR, estimated glomerular filtration rate (TIF 1134 KB)

10147_2021_1988_MOESM4_ESM.tif

Supplementary file4 Supplementary Figure 1. Survival curves for outcomes of the non-radical cystectomy group according to prognostic factors. Survival curves for progression-free survival in the non-radical cystectomy group according to eGFR (a) and tumor size (b). Survival curves for cancer-specific survival according to tumor size (c). Survival curves for overall survival according to eGFR (d), tumor size (e), and variant histology (f). Abbreviations: eGFR, estimated glomerular filtration rate (TIF 786 KB)

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Iida, K., Miyake, M., Murakami, K. et al. Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer outcomes in patients without radical cystectomy. Int J Clin Oncol 26, 2104–2112 (2021). https://doi.org/10.1007/s10147-021-01988-8

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  • DOI: https://doi.org/10.1007/s10147-021-01988-8

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