Estimating recurrence free survivability of Non-Muscle Invasive Bladder Cancer (NMIBC) after intravesical therapy: A clinical-based recursive partition analysis

5080 Background: Our initial phase I trial showed docetaxel to be a safe agent for intravesical therapy with no systemic absorption and minimal toxicity after 6 weekly instillations. In that trial, docetaxel appeared to show a 56% complete response (CR) but the durability was only 22% (no additional therapy) to 39% (CR with additional TURBT). Owing to this excellent initial response rate, a second group of patients were treated with a 6 week induction and then given monthly maintenance therapy with intravesical docetaxel for BCG refractory high-grade, non-muscle invasive bladder cancer (NMIBC). Methods: 13 patients with recurrent Ta (n=1), T1 (n=6), and Tis (n=6) TCC who failed at least one prior BCG treatment were treated. Induction therapy was administered to all 13 patients as 6 weekly instillations of 75mg intravesical docetaxel followed by single-dose monthly maintenance therapy for 9 additional instillations in 9 of the patients who experienced complete initial response. Initial response at 12 weeks from the start of induction therapy was evaluated by cystoscopy with biopsy and urine cytology. Follow-up consisted of quarterly cystoscopy with biopsy and cytology and periodic CT scans. Results: The median follow-up was 14.4 months for the entire cohort. Median duration of maintenance treatment was 9 months. 10/13 patients (77%) from the entire cohort had a complete initial response after induction, and 6/13 patients (46%) have remained disease-free in follow-up. Of those who failed, 6 patients underwent TURBT and one underwent cystectomy. 9/10 initial responders completed at least 3 doses of maintenance therapy to date, of whom 6/9 (67%) have remained recurrence-free. Conclusions: Monthly maintenance therapy with intravesical docetaxel appears to extend the durability of response to induction treatment for a select group of patients with BCG refractory high risk NMIBC and may decrease overall risk of recurrence in NMIBC. No significant financial relationships to disclose.

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Multi-institutional review of sequential intravesical gemcitabine and mitomycin C chemotherapy for non-muscle-invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.294 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 294-294

Author(s):

Andrew J. Lightfoot ◽

Benjamin N. Breyer ◽

Henry M. Rosevear ◽

Badrinath Konety ◽

Michael A. O'Donnell

Keyword(s):

Bladder Cancer ◽

Mitomycin C ◽

Median Time ◽

Combination Chemotherapy ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Recurrence Free Survival ◽

Muscle Invasive Bladder Cancer ◽

Free Survival ◽

Muscle Invasive

294 Background: Combination chemotherapy is the standard of care for neoadjuvant, adjuvant, and metastatic bladder cancer due to increased efficacy when compared to monotherapy. We report our experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for non-muscle invasive bladder cancer (NMIBC). Methods: We performed a multi-institutional retrospective review of 47 consecutive patients who received 6 weekly treatments with sequential gemcitabine (1g) and mitomycin C (40mg) chemotherapy for NMIBC. Thirty patients received treatment at University of Iowa, 14 at UCSF and 3 at University of Minnesota. Results: A total 47 patients (median age 70, range 32-85; 36 males, 11 females) previously failing a median of 2 intravesical treatments were reviewed. The complete response (CR), 1-year recurrence-free survival (1-RFS) and 2-year recurrence-free survival (2-RFS) for all patients was 68%, 48% and 38%, respectively. In all, 14 of 47 patients (30%) remain free of recurrence with a median time to followup of 26 months (range 6-80 months). The median time to recurrence for all patients who recurred was 4 months (range 1-33 months). Ten patients required cystectomy. Conclusions: Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with a history of NMIC which has failed BCG or other intravesical therapy, in addition to patients with intermediate and high-risk disease.

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The impact of different adjuvant intravesical therapy methods on tumor biology in patients with high-risk non-muscle-invasive bladder cancer

Central European Journal of Urology ◽

10.5173/ceju.2021.0122 ◽

2021 ◽

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Tumor Biology ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive ◽

The Impact

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Canadian guidelines for treatment of non-muscle invasive bladder cancer: a focus on intravesical therapy

Canadian Urological Association Journal ◽

10.5489/cuaj.846 ◽

2013 ◽

Vol 4 (3) ◽

pp. 168

Author(s):

Wassim Kassouf ◽

Ashish M. Kamat ◽

Alexander Zlotta ◽

Bernard H. Bochner ◽

Ronald Moore ◽

...

Keyword(s):

Bladder Cancer ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

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Critical Questions To Optimize Intravesical Therapy for Non–muscle-invasive Bladder Cancer

European Urology Focus ◽

10.1016/j.euf.2018.09.004 ◽

2018 ◽

Vol 4 (4) ◽

pp. 463

Author(s):

Peter Black

Keyword(s):

Bladder Cancer ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Muscle Invasive Bladder Cancer ◽

Critical Questions ◽

Muscle Invasive

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Tumor burden reduction in an orthotopic non-muscle-invasive bladder cancer model using IL-15 analogue (ALT-803) targeting T regulatory cells.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.298 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 298-298

Author(s):

Evan Gomes ◽

Makito Miyake ◽

Ge Zhang ◽

Steve Goodison ◽

Jack Egan ◽

...

Keyword(s):

Bladder Cancer ◽

Nk Cells ◽

Tumor Burden ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Cancer Model ◽

Muscle Invasive Bladder Cancer ◽

Bcg Therapy ◽

Muscle Invasive ◽

Bladder Cancer Model

298 Background: A recent NCI review listed IL-15 as the most promising product candidate among twelve immunotherapy drugs that could potentially cure cancer. Preclinical studies using ALT-803 (mutated IL-15 analogue combined with IL-15Rα-Fc fusion) have shown promising results for obtaining prolonged drug half-life and stimulating CD8+ T cells and NK cells. Based on these results, we hypothesized that the administration of ALT-803 will generate an immunologic response which will reduce tumor burden in a rodent carcinogen induced orthotopic non muscle invasive bladder cancer model (NMIBC). Methods: We tested intravesical ALT-803 alone and ALT-803 in combination with Bacillus Calmette-Guérin (BCG) in a rodent carcinogen induced orthotopic NMIBC model. Rats were anesthetized then a 22-gauge Teflon transurethral catheter was placed in the bladder and urine completely drained from the bladder. Next, the saline (negative control), ALT-803 (experimental agent) or BCG (positive control) therapy was delivered by transurethral instillation and allowed to dwell in the bladder for 1 hr by occlusion of the urethra with a purse string suture. The intravesical therapy was administered weekly for a total of six weeks to mimic intravesical BCG therapy in humans. Results: Herein we demonstrate that ALT-803 was safe and well tolerated alone or in combination with BCG. Furthermore, ALT-803 alone reduced tumor burden by 23% whereas BCG alone reduced tumor burden by 11% compared to control. The combination of ALT-803 and BCG reduced tumor burden by 30% compared to control. Tumoral responses of the combinational treatment were associated with 76% and 80% reduction in angiogenesis and proliferation, respectively, whereas combinational therapy was associated with a 7.7-fold increase in apoptotic index compared to control. Immune monitoring suggested that the antitumor response was linked to the activation of CD8+ cells and NK cells. Conclusions: The enhanced therapeutic index provided by ALT-803 plus BCG therefore provides a powerful justification for the development of this agent for future clinical trials in subjects with non-muscle invasive bladder cancer.

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