Urovysion™ testing can lead to early identification of intravesical therapy failure in patients with high risk non-muscle invasive bladder cancer

Management of patients with cacillus Calmette–Guérin (BCG)-unresponsive, high-risk, non-muscle-invasive bladder cancer (NMIBC) presents a formidable clinical challenge that requires urologists to weigh the competing risks of progression during further intravesical therapy vs. the morbidity of radical cystectomy. The prognosis of high-risk NMIBC recurring after BCG depends on the adequacy of prior BCG, the timing of recurrence, and tumor histology. The standard of care is currently radical cystectomy, as effective salvage intravesical therapy has not been established. The development of bladder-sparing treatments has been hampered to date by inconsistent definitions of BCG failure and difficulties in identifying appropriate control treatments in clinical trials. Despite these limitations, the spectrum of salvage therapy is expanding to include enhanced intravesical chemo-, gene, and immuno-therapies. In this review, we provide an overview of these emerging agents in the context of our current understanding of BCG failure and the unique considerations for clinical trial design in this disease state.

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BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301)

BMC Cancer ◽

10.1186/s12885-015-1431-6 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 8

Author(s):

Dickon Hayne ◽

Martin Stockler ◽

Steve P. McCombie ◽

Venu Chalasani ◽

Anne Long ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Mitomycin C ◽

Phase Iii ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Muscle Invasive Bladder Cancer ◽

Phase Iii Trial ◽

Muscle Invasive

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Tumor mutation burden to predict progression in high-risk non-muscle invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.397 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 397-397

Author(s):

Joshua Meeks ◽

Benedito A. Carneiro ◽

Sachin Gopalkrishn Pai ◽

Daniel Oberlin ◽

Alfred Rademaker ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Loss Of Function ◽

Metastatic Tumors ◽

Muscle Invasive Bladder Cancer ◽

Primary Tumors ◽

Comparison Results ◽

Muscle Invasive

397 Background: The genetic mechanisms associated with progression of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have not been described. We conducted next-generation sequencing (NGS) of HR-NMIBC and compared the genomic profiles of cancers that responded to intravesical therapy and those that progressed to muscle-invasive or advanced disease. Methods: DNA was extracted from formalin-fixed paraffin-embedded sections of tumor from 25 patients with HR-NMIBC (23 with T1HG; 3 with TaHG and carcinoma in situ). Ten patients with HR-NMIBC developed progression (pT2+ or N+) (“progressors”). Fifteen patients had no progression (“non-progressors”). Tissue from 11 patients with metastatic bladder cancer (BC) were analyzed for comparison. Results: We identified no difference in the frequency of mutations of TP53, PIK3CA, or KMT2D between the primary tumors of progressors compared to non-progressors and metastatic tumors. An increased frequency of mutations and deletions causing loss of function of CDKN2A and CDKN2B was identified in tumors at progression (37%) compared to non-progressors (6%) (p=0.10). We found a significant decrease in total mutational burden (TMB) comparing non-progressors, progressors and metastatic tumors at 15, 10.1 and 5.1 mutations/MB respectively (p=0.02). This association suggests more advanced tumors have decreased neoantigen burden and may potentially explain the mechanism of BCG response in non-progressors. Conclusions: TMB was significantly greater in non-progressors compared to progressors. We found no novel genetic drivers in tumors that progressed and HR-NMIBC had many genetic features similar to metastatic BC. The loss of CDKN2A appears to occur late in the process of invasion of BC and may represent an important step in progression. Further research is necessary to evaluate loss of CDKN2A as a biomarker for progression of NMIBC.

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MP73-13 MULTI-INSTITUTIONAL OUTCOMES OF PATIENTS WITH HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) WHO UNDERGO RADICAL CYSTECTOMY AFTER BCG AND SUBSEQUENT SALVAGE INTRAVESICAL THERAPY

The Journal of Urology ◽

10.1097/ju.0000000000000959.013 ◽

2020 ◽

Vol 203 ◽

pp. e1126-e1127

Author(s):

Vignesh T. Packiam* ◽

Craig V. Labbate ◽

Stephen A. Boorjian ◽

Robert F. Tarrell ◽

Brittany Adamic ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Radical Cystectomy ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

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Electromotive Drug Administration of Mitomycin C (EMDA/MMC) versus Intravesical Immunotherapy with Bacillus Calmette-Guérin (BCG) in Intermediate and High Risk Non Muscle Invasive Bladder Cancer

Urologia Internationalis ◽

10.1159/000520630 ◽

2021 ◽

pp. 1-8

Author(s):

Michele Zazzara ◽

Arjan Nazaraj ◽

Marcello Scarcia ◽

Giuseppe Cardo ◽

Roberto Carando ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Adjuvant Therapy ◽

Adjuvant Treatment ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Progression Rate ◽

Muscle Invasive Bladder Cancer ◽

Free Survival ◽

Muscle Invasive

Background: Although TURB of tumor (TURBT) by itself can eradicate a non-muscle-invasive bladder cancer (NMIBC) completely, these tumors commonly recur and can progress to MIBC. It is, therefore, necessary to consider adjuvant therapy in most patients. The primary objective of the present study was to report our experience with EMDA/MMC and BCG, considering efficacy, progression, and recurrence, as adjuvant therapy in NMIBC patients; the secondary objective was to assess the efficacy of EMDA/MMC versus BCG as a comparative treatment. Methods: Between April 2016 and February 2020, a series of 216 patients, with a diagnosis of intermediate- and high-risk NMIBC after TURBT, underwent adjuvant intravesical therapy. In 26 cases with a failure of the treatment, in patients unfit and unwilling for radical cystectomy, a repeated intravesical therapy was performed (2 had a twice repetition). Out of 244 adjuvant therapies, 140 EMDA/MMC and 104 BCG treatments were done. The following data were collected for each patient: baseline demographics and clinical data and perioperative and postoperative data. Overall patients’ adjuvant intravesical therapies were included in a prospectively maintained institutional database, and a retrospective chart review was performed. We collected data on 2 main outcomes, recurrence-free survival (defined as a negative cystoscopy, cytology, and/or histology at the evaluation time point) and progression-free survival (defined as a negative cystoscopy or a nonprogressive tumor recurrence). Results: The NMIBC progression rate was higher in BCG than EMDA/MMC but not statistically significant (respectively, 4.2% vs. 2.5%; p = 0.703). In the overall population, the risk of NMIBC recurrence was higher after BCG than EMDA/MMC (p = 0.025). In the subgroups of 59 paired patients with similar characteristics, no difference was observed between groups in NMIBC progression and recurrence. Conclusions: Our findings suggest that EMDA/MMC and BCG are safe and reproducible approaches as adjuvant treatment in NMIBC. EMDA/MMC permits to achieve a fine oncological management as adjuvant treatment in NMIBC, which is not less than that obtained with BCG.

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