Transurethral Resection and Sequential Chemo&amp;ndash;Immunoprophylaxis in Primary T1G3 Bladder Cancer

Bono, Aldo; Lovisolo, J.; Saredi, Giovanni

doi:10.1159/000020171

Cited by 22 publications

(6 citation statements)

References 22 publications

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“…Sequential treatment with BCG and chemotherapeutic agents, particularly ADM, induced IL-17 and G-CSF systemically. The summary of this study is displayed in Table II shows a summary of previous prospective studies involving intravesical sequential treatment with BCG and chemotherapeutic agents for patients with NMIBC (10)(11)(12)(13)(14)(15)(16)(17)(19)(20)(21)(27)(28)(29)(30)(31)(32). Intravesical sequential treatment has been studied since the 1990s, with the studies mainly focusing on the effects of chemotherapeutic agents, such as direct antitumor effects, tissue-scarifying of the bladder surface for attachment of BCG to the bladder wall, and the reduction of adverse events induced by BCG.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Sequential chemoimmunoprophylaxis has been investigated in a few reports. Bono et al [12] evaluated the benefit of a chemo-immunotherapy consisting of weekly epirubicin for 8 weeks followed by weekly BCG for 6 weeks. Their study included 81 patients undergoing TUR for primary T1G3 tumour.…”

Section: © 2 0 0 4 B J U I N T E R N a T I O N A Lmentioning

confidence: 99%

T1G3 transitional cell carcinoma of the bladder: recurrence, progression and survival

Peyromaure

Zerbib

2003

BJU International

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age. Patients treated with BCG had systematic biopsies taken at the end of the first course. Patients with residual tumour received a second course of six weekly instillations. Patients with negative biopsies received maintenance BCG therapy consisting of intravesical instillations each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months after the first course. RESULTSThe median follow-up was 53 months. The overall recurrence rate was 46% and the overall progression rate 19%. The rate of delayed cystectomy was 8% and that of disease-specific survival 91%. In patients who received BCG therapy, the recurrence and progression rates were 42% and 23%, respectively. In this group the rate of diseasespecific survival was 88%. CONCLUSIONThis study confirms that maintenance BCG therapy is an effective treatment for T1G3 bladder tumours, with an acceptable rate of bladder preservation.

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“…[18] Several different combinations and sequences of administration of intravesical agents are being evaluated to see if any can offer benefits over BCG alone. Although one of these studies has demonstrated a tumor progression rate as low as 7.4%,[19] none of these studies have convincingly demonstrated any incremental reduction in tumor progression compared to BCG alone. As a result, induction and maintenance BCG therapy is the most effective intravesical agent for preventing progression and is equivalent to other therapies in preventing recurrences in T1G3 disease.…”

Section: Case Against Cystectomymentioning

confidence: 99%

Pros and cons of radical cystectomy in the treatment of T1G3 bladder cancer

Agarwal

Kamat

2008

Indian J Urol

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The management of T1G3 (or high-grade T1) bladder cancer poses a challenging clinical dilemma to the urologist. There are good data supporting bladder conservative therapy with repeat transurethral resection and administration of Bacille Calmette-Guérin (BCG) intravesical therapy but this must include maintenance regimens since only maintenance BCG has been shown to decrease tumor recurrence and progression. Concern over worse survival with a delay in definitive therapy has prompted many to recommend immediate cystectomy for T1G3 disease. Ultimately, the decision needs to be individualized and although certain pathologic factors (T1b disease, early recurrence or progression within three months of BCG therapy, lymphovascular invasion and variant histology) are prognostic of progressive disease, no definitive risk factors for tumor progression have been identified.

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Transurethral Resection and Sequential Chemo–Immunoprophylaxis in Primary T1G3 Bladder Cancer

Cited by 22 publications

References 22 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

T1G3 transitional cell carcinoma of the bladder: recurrence, progression and survival

Pros and cons of radical cystectomy in the treatment of T1G3 bladder cancer

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