Insignificant role of bacillus Calmette–Guérin maintenance therapy after complete transurethral resection of bladder tumor for intermediate‐ and high‐risk non‐muscle‐invasive bladder cancer: Results from a randomized trial

Nakai, Yasushi; Anai, Satoshi; Tanaka, Nobumichi; Chihara, Yoshitomo; Haramoto, Masaki; Otani, Takeshi; Nakagawa, Yasuaki; Hirao, Yoshihiko; Konishi, Noboru; Fujimoto, Kiyohide

doi:10.1111/iju.13167

Cited by 11 publications

(13 citation statements)

References 27 publications

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“…Despite improved management for decreasing the recurrence rate and prolonging the progression-free interval, NMIBC exhibits significant potential of recurrence intravesically and progression to muscle-invasive bladder cancer (5,6). Although intravesical treatment with BCG represents the most effective and common form of adjuvant therapy for high risk NMIBC, BCG-failure NMIBC is the one of main problems in the management of UCB (7)(8)(9). Thus, clinical management of high-risk NMIBC remains challenging and further advancements in treatment initiation and maintenance are urgent.…”

Section: Introductionmentioning

confidence: 99%

Intravesical treatment of chemotherapeutic agents sensitizes bacillus Calmette‑Guerin by the modulation of the tumor immune environment

et al. 2019

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Intravesical treatment with bacillus Calmette-Guerin (BCG) is the most common treatment for preventing progression and recurrence of non-muscle invasive bladder cancer. Our previous study using the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer model demonstrated that intravesical treatment with mitomycin C (MMC) and adriamycin (ADM) suppressed pro-tumoral immunity, including the aggregation of tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) in the tumor microenvironment. Previous evidence supports the association of resistance to intravesical treatment of BCG with TAMs and Tregs. In the present study, we investigated the antitumoral efficacy of sequential intravesical treatments with chemotherapeutic agents and BCG in a BBN-induced orthotopic bladder cancer model. Thirty-six C57BL/6J mice bearing bladder cancer were randomly divided into six treatment groups as follows: Control, BCG, MMC, ADM, MMC-BCG and ADM-BCG. Intravesical treatment was performed once a week for six weeks. One week after the completion of intravesical treatment, bladder and blood were harvested. MMC-BCG and ADM-BCG were more effective antitumor activities than BCG monotherapy. Bladders were subjected to immunohistochemical analysis and revealed that intravesical BCG treatment combined with MMC/ADM promoted the local recruitment of NK cells to the bladder as effectively as BCG monotherapy and reduced TAMs and Tregs in the bladder. Interleukin (IL)-17 and granulocyte-colony stimulating factor (G-CSF) in serum were analyzed by enzyme-linked immunosorbent assay and these levels were revealed to be elevated in mice treated with sequential treatments similar to levels following monotherapy with MMC and ADM. Our findings indicated that intravesical sequential treatment could suppress the resistance to BCG through the enhancement of antitumor immunity (induction of NK cells) and inhibition of pro-tumoral immunity (reduction of TAMs and Tregs). Systemic changes in IL-17 and G-CSF may be involved in topical immunomodulation. Further studies including clinical trials may be required to establish an appropriate strategy based on the immunomodulation of the tumor microenvironment.

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Section: Introductionmentioning

confidence: 99%

Intravesical treatment of chemotherapeutic agents sensitizes bacillus Calmette‑Guerin by the modulation of the tumor immune environment

et al. 2019

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“…However, the effective dose, duration, and strain of BCG for intravesical instillation have not yet been clearly determined. Although a number of RCTs have assessed the differences of clinical outcomes according to dose (standard vs low), [ 12 – 19 ] duration (induction vs maintenance), [ 20 – 27 ] and strain of BCG [ 28 – 30 ] in NMIBC, conflicting results have prevented any consensus concerning the effective BCG strategy.…”

Section: Introductionmentioning

confidence: 99%

Dose, duration and strain of bacillus Calmette–Guerin in the treatment of nonmuscle invasive bladder cancer

Yongjun

Jeong²,

Kwak³

et al. 2017

Medicine

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“…11 Recurrence-/progression-free survival did not improve in the maintenance cohort when compared with the non-maintenance cohort. 11 It is difficult to completely eradicate the recurrence of high-risk NMIBC, even by maintenance BCG instillation combined with complete TURBT, and a significant number of high-risk NMIBC are flat tumors similar to CIS. Perhaps, regardless of abnormal cystoscopic appearance, all NMIBC patients with positive cytology could be possible candidates for additional random biopsies.…”

Section: Presence Of Concomitant Cis or High-risk Nmibcmentioning

confidence: 90%

“…Nakai et al . investigated the role of maintaining BCG instillation for the intermediate‐/high‐risk NMIBC receiving aggressive complete TURBT . Recurrence‐/progression‐free survival did not improve in the maintenance cohort when compared with the non‐maintenance cohort .…”

Section: Principles Of Bladder Preservationmentioning

confidence: 99%

“…investigated the role of maintaining BCG instillation for the intermediate‐/high‐risk NMIBC receiving aggressive complete TURBT . Recurrence‐/progression‐free survival did not improve in the maintenance cohort when compared with the non‐maintenance cohort . It is difficult to completely eradicate the recurrence of high‐risk NMIBC, even by maintenance BCG instillation combined with complete TURBT, and a significant number of high‐risk NMIBC are flat tumors similar to CIS.…”

Section: Principles Of Bladder Preservationmentioning

confidence: 99%

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Can bladder preservation therapy come to the center stage?

et al. 2017

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Decision-making in urological cancer care requires a multidisciplinary approach for refinement, but its impact on urothelial carcinoma of the bladder has not been fully addressed for the past three decades, except for the latest immunological checkpoint inhibitor approved by the U.S. Food and Drug Administration for metastatic muscle-invasive bladder cancer that is resistant to platinum-based chemotherapy. For the time being, radical cystectomy is the gold standard of curative therapy for muscleinvasive bladder cancer. Trimodal therapy that combines chemotherapy for the purpose of radiation sensitization, external beam radiotherapy and transurethral resection of bladder tumor has emerged as a potential alternative treatment option that preserves the bladder. In lack of randomized studies for bladder preservation therapy compared with surgery, the principles of management of urothelial carcinoma of the bladder have evolved in recent times, with an emphasis on bladder preservation. A number of bladder preservation techniques are available to the surgeon; however, appropriately selected patients with muscle-invasive bladder cancer should be offered the opportunity to discuss various treatment options, including organ-sparing trimodal therapy. The aim of the present study was to compare the primary outcomes of the available treatment methods and identify the sources of variance among studies. A review of various bladder preservation techniques in vogue for the management of urothelial carcinoma of the bladder is discussed.

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Insignificant role of bacillus Calmette–Guérin maintenance therapy after complete transurethral resection of bladder tumor for intermediate‐ and high‐risk non‐muscle‐invasive bladder cancer: Results from a randomized trial

Abstract: Bacillus Calmette-Guérin maintenance therapy did not improve recurrence- and progression-free survival rates after the initial complete transurethral resection of bladder tumors compared with that after bacillus Calmette-Guérin induction therapy alone.

Cited by 11 publications

References 27 publications

Intravesical treatment of chemotherapeutic agents sensitizes bacillus Calmette‑Guerin by the modulation of the tumor immune environment

Intravesical treatment of chemotherapeutic agents sensitizes bacillus Calmette‑Guerin by the modulation of the tumor immune environment

Dose, duration and strain of bacillus Calmette–Guerin in the treatment of nonmuscle invasive bladder cancer

Can bladder preservation therapy come to the center stage?

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