Treatment Options in Superficial (pTa/pT1/CIS) Bladder Cancer

2008 ◽  
pp. 118-137
Author(s):  
J. L. Ockrim ◽  
P. D. Abe
Keyword(s):  
Bladder Cancer ◽  
Treatment Options

scholarly journals The dynamics of the inflammatory response during BBN-induced bladder carcinogenesis in mice

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Marina Degoricija ◽  
Jelena Korac-Prlic ◽  
Katarina Vilovic ◽  
Tonci Ivanisevic ◽  
Benedikt Haupt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Inflammatory Response ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Locally Advanced ◽  
Histopathological Analysis ◽  
Tumor Escape ◽  
Induced Tumors ◽  
Frequent Mutations ◽  
Muscle Invasive

Abstract Background Bladder cancer (BC) is the most common malignant disease of the urinary tract. Recurrent high grade non muscle invasive BC carries a serious risk for progression and subsequent metastases. The most common preclinical mouse model for bladder cancer relies on administration of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) to mice. BBN-induced tumors in mice recapitulate the histology of human BC and were characterized with an overexpression of markers typical for basal-like cancer subtype in addition to a high mutational burden with frequent mutations in Trp53, similar to human muscle invasive BC. Methods Bladder cancer was induced in C57BL/6J male mice by administering the BBN in the drinking water. A thorough histopathological analysis of bladder specimen during and post BBN treatment was performed at 2, 4, 16, 20 and 25 weeks. RNA sequencing and qPCR was performed to assess the levels of expression of immunologically relevant genes at 2 weeks and 20 weeks during and post BBN treatment. Results We characterized the dynamics of the inflammatory response in the BBN-induced BC in mice. The treatment with BBN had gradually induced a robust inflammation in the first 2 weeks of administration, however, the inflammatory response was progressively silenced in the following weeks of the treatment, until the progression of the primary carcinoma. Tumors at 20 weeks were characterized with a marked upregulation of IL18 when compared to premalignant inflammatory response at 2 weeks. In accordance with this, we observed an increase in expression of IFNγ-responsive genes coupled to a pronounced lymphocytic infiltrate during the early stages of malignant transformation in bladder. Similar to human basal-like BC, BBN-induced murine tumors displayed an upregulated expression of immunoinhibitory molecules such as CTLA-4, PD-L1, and IDO1 which can lead to cytotoxic resistance and tumor escape. Conclusions Despite the recent advances in bladder cancer therapy which include the use of checkpoint inhibitors, the treatment options for patients with locally advanced and metastatic BC remain limited. BBN-induced BC in mice displays an immunological profile which shares similarities with human MIBC thus representing an optimal model for preclinical studies on immunomodulation in management of BC.

Bladder cancer

2019 ◽  
Vol 13 (6) ◽  
pp. 271-277
Author(s):  
Ian Peate
Keyword(s):  
Bladder Cancer ◽  
Treatment Options ◽  
Older Person ◽  
Multiple Choice Questions ◽  
Men And Women ◽  
Treatment Regimens ◽  
Common Cancer ◽  
The One ◽  
The Uk

This article is the one in the cancer series that discusses bladder cancer. Bladder cancer can occur in men and women; however, in the UK, there are more men with bladder cancer than women. It is also a disease of the older person. This article provides an introduction that discusses the condition. An overview of the anatomy of the bladder and ureters is provided. In 2015, bladder cancer was the 10th most common cancer in the UK and was responsible for 3% of all new cancer cases. Diagnosis and treatment options are discussed, with an emphasis on ensuring that the patient is key in any decisions that are made about treatment regimens. The importance of follow-up after treatment is also discussed. A glossary of terms is provided and five multiple-choice questions are included to enhance learning and application to practice.

Impact of multidisciplinary bladder cancer care for muscle invasive bladder cancer: A propensity score matched analysis of survival outcomes.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 455-455 ◽  
Author(s):  
Girish S. Kulkarni ◽  
Thomas Hermanns ◽  
Kathy Li ◽  
Yanliang Wei ◽  
Bimal Bhindi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Treatment Options ◽  
Cox Proportional Hazards ◽  
Survival Outcomes ◽  
Primary Therapy ◽  
Bladder Preservation ◽  
Trimodal Therapy ◽  
Significant Difference

455 Background: We started in 2008 a Multidisciplinary Bladder Cancer Clinic (MDBCC), where complex bladder cancer patients are assessed concurrently by urologic and radiation oncologists, with support from medical oncologists. Patients have the opportunity to discuss various treatment options including radical cystectomy (RC) or bladder sparing trimodal therapy (TMT; endoscopic resection, radiotherapy and chemotherapy). Although reports have shown comparable outcomes of TMT to cystectomy, no direct comparison to RC has been published and no randomized studies are available. We report our long term outcomes of multidisciplinary care, comparing TMT to surgery using propensity-matched analyses. Methods: Patients seen in our MDBCC receiving TMT for MIBC from 2008 to 2012 were identified and matched, using propensity scores, to patients operated by RC. Matching occurred on age, ECOG status, Charlson comorbidity score, cT stage, cN stage and date of treatment. Overall survival (OS) and disease-specific survival (DSS) were assessed with Cox Proportional hazards modeling and competing risk analysis, respectively. Results: Between 2008 and 2012, 248 patients were assessed in the MDBCC. Of these, 162 (65%) had MIBC. Nearly half (80) opted for radiotherapy +/- concurrent cisplatin chemotherapy and 49 underwent full bladder preservation with TMT as their primary therapy. We matched 48 TMT patients with 48 RC patients with no imbalances. Median age of the cohort was 67.5 years with 29.2% cT3/cT4. With a median follow up time of 3.62 years, there were 19 (39.6%) deaths (7 from bladder cancer) in the RC group and 15 (31.3%) deaths (6 from bladder cancer) in the TMT group. 5 year DSS was 85.2% and 84.7% with TMT and surgery, respectively (p > 0.05). There was no statistically significant difference in DSS between the two groups (HR for TMT 1.31 (0.40-4.23), p = 0.66) or in OS (HR for TMT 0.77 (0.34-1.75), p = 0.53). Conclusions: Bladder cancer patients benefit from a multidisciplinary approach.. In selected patients with MIBC, chemo-radiation yields survival outcomes similar to matched RC patients. BC patients should be offered the possibility to discuss various treatment options.

Results after two years of follow up after intravesical thermochemotherapy with heated mitomycin 40 in patients with high-risk superficial bladder cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 512-512
Author(s):  
Thomas Alexander Voegeli ◽  
Eric Frank ◽  
Christian Bach ◽  
Catejan Nzeh
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Alternative Treatment ◽  
Superficial Bladder Cancer ◽  
Treatment Options ◽  
High Rate ◽  
Intravesical Therapy ◽  
Bladder Irrigation ◽  
Metastatic Prostate Carcinoma

512 Background: Standard management of high risk TCC is either BCG or radical cystectomy, alternative treatment options are limited. It is known that the anti-tumor effect of heated mitomycin is 10 fold higher than at room temperature, which is the standard of intravesical therapy. We herein report the first 2 year follow up (FU) after intravesical therapy with heated mitomycin in a cohort of patients with high risk superficial bladder cancer (TCC). Methods: Treatment was performed for 1 hour with machine bladder irrigation (COMBAT) which maintaines temperature of mitomycin (40 mg) exactly at 43 C. Patients underwent therapy with a 6 week course of weekly treatment and were than followed by cystoscopy every 3 month and if necessary biopsy. Results: We identified 62 patients out of a total group of 108 patients who met the inclusion criteria for high risk TCC according to the EAU Guidelines and who got the complete 6 courses of treatment. 2 were lost of follow up, 1 died due to cardiac problems and 1 from metastatic prostate carcinoma. The remaining 58 patients had a mean FU of 26 month (16-54 m) and included 20 non-responders to BCG. 48/58 patients had CIS or pT1 Tumors or both, 10 patients had pTa+CIS. There were 5 recurrences, all superficial stage pTa, one in the rigth ureter, all could be managed without cystectomy. 8 patients had progressive or recurrent CIS/pT1 or were progressive to pT2 after therapy and underwent cystectomy. Conclusions: In this high risk cohort of 58 patients with a high rate of BCG non-responders only 8 patients had to undergo cystectomy during a 2 year follow up. Intravesical therapy with heated mitomycin is safe and well tolerated and may be an additional alternative treatment before cystectomy is performed in high risk patients with high risk TCC or BCG non responders.

scholarly journals Recognition and Treatment of BCG Failure in Bladder Cancer

2011 ◽  
Vol 11 ◽  
pp. 602-613 ◽  
Author(s):  
Andrew J. Lightfoot ◽  
Henry M. Rosevear ◽  
Michael A. O'Donnell
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Treatment Options ◽  
Standard Of Care ◽  
Complete Response ◽  
Bcg Therapy ◽  
Risk Patients ◽  
Bcg Failure ◽  
Muscle Invasive ◽  
American Urological Association

Patients with high-grade Ta, T1, or carcinomain situnon–muscle-invasive bladder cancer (NMIBC) are at high risk for recurrence and, more importantly, progression. Thus, both the American Urological Association and European Association of Urology recommend initial intravesical treatment with bacillus Calmette-Guerin(BCG) followed by maintenance therapy for a minimum of 1 year. The complete response rate to BCG therapy in patients with high-risk NMIBC can be as high as ∼80%; however, most patients with high-risk disease suffer from recurrence. BCG failure can be further characterized into BCG refractory, BCG resistant, BCG relapsing, and BCG intolerant. Current recommendations include one further course of BCG or cystectomy. In patients who continue to fail conservative treatment and who refuse surgical therapy or are not surgical candidates, treatment options become even more complicated. In this setting, treatment options are limited and include repeat BCG treatment, an alternate immunotherapy regimen, chemotherapy, or device-assisted therapy. To date, however, further research is necessary for all secondary treatment options in order to determine which might be the most efficacious. All conservative treatments should be considered investigational. Currently, cystectomy remains the standard of care for high-risk patients who have failed BCG therapy.

scholarly journals Significant Benefit of Everolimus In a Patient With Urothelial Bladder Cancer Harboring A Rare M1043I Mutation of PIK3CA

2021 ◽  
Author(s):  
Shouhua Pan ◽  
Si Li ◽  
Mingzhe Xiao ◽  
Dongsheng Chen ◽  
Junlong Li
Keyword(s):  
Bladder Cancer ◽  
Treatment Options ◽  
Complete Response ◽  
Significant Benefit ◽  
Urothelial Bladder Cancer ◽  
Multiple Tumor ◽  
First Line Therapy ◽  
First Case ◽  
Potential Biomarker ◽  
Urothelial Bladder

Abstract Urothelial bladder cancer (UBC) is a common malignancy with significant mortality worldwide. However, treatment options of UBC were mainly chemotherapy and immunotherapy since few targeted agents had shown efficacy in UBC. In recent studies, everolimus has showed antitumor activity in patients harboring aberrations in PI3K/Akt/mTOR pathway in multiple tumor types. Here we report a patient with metastatic UBC harboring a rare M1043I mutation of PIK3CA detected by DNA based next-generation sequencing. The patient received everolimus as first-line therapy after palliative transurethral resection. Within one months, the residual lymph node metastases achieved complete response and no more ostealgia was reported. To our knowledge, this is the first case reporting a significant benefit from everolimus in PIK3CA mutant UBC, suggesting the rare M1043I mutation variant may be a potential biomarker of sensitivity to everolimus. Further mechanism insights and clinical studies are needed to clarify the effectiveness of everolimus in patients with PIK3CA M1043I mutation.

A randomized phase II study of erdafitinib (ERDA) versus intravesical chemotherapy (IC) in patients with high-risk nonmuscle invasive bladder cancer (HR-NMIBC) with FGFR mutations or fusions, who recurred after Bacillus Calmette-Guérin (BCG) therapy.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS603-TPS603 ◽  
Author(s):  
Gary D. Steinberg ◽  
Joan Palou-Redorta ◽  
Juergen E. Gschwend ◽  
Ben Tran ◽  
Yohann Loriot ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Treatment Options ◽  
Complete Response ◽  
Disease Recurrence ◽  
Subsequent Treatment ◽  
Invasive Bladder Cancer ◽  
Open Label ◽  
Bcg Therapy ◽  
Us Fda ◽  
To Receive

TPS603 Background: ERDA, an oral pan-FGFR inhibitor, is approved by the US FDA for metastatic urothelial carcinoma (mUC) with susceptible FGFR3 or FGFR2 gene alterations and progressed on/ or after at least 1 line of prior platinum-containing chemotherapy (PCC) including within 12 months of neoadjuvant/adjuvant PCC.1 Around 40% of patients with bladder cancer present with HR-NMIBC. First-line BCG therapy fails in 30-40% of patients and subsequent treatment options are limited. This study is designed to evaluate recurrence-free survival (RFS) following treatment with ERDA vs IC in patients with FGFR positive HR-NMIBC who recurred after BCG therapy. Methods: This is an open-label, multicenter, randomized, phase 2, safety and efficacy study of ERDA in adults with histologically confirmed HR-NMIBC and FGFR mutations or fusions. Inclusion criteria: ECOG status ≤1, adequate bone marrow, liver, renal function, and ineligibility for or declining cystectomy, with no history of prior FGFR inhibitors. Patients will be enrolled into 1 of 3 cohorts. Cohort 1 (n=240): high-grade disease Ta/T1 lesion (papillary only) with disease recurrence after BCG therapy will be randomized to ERDA or IC (investigator choice: gemcitabine or mitomycin C); Cohort 2 (n=20): carcinoma in situ (CIS) with/without papillary disease to receive ERDA monotherapy; Cohort 3 (n=20): marker lesion study in patients with intermediate-risk papillary disease only to receive ERDA monotherapy. Dose will be maintained at 8 mg, up-titrated to 9 mg, or withheld based on phosphate levels. Primary endpoint: Cohort 1- RFS; Secondary endpoints: Cohort 1 - time to progression and disease worsening, disease-specific survival (invasive bladder cancer), overall survival, RFS rate at 6, 12, 24 months, and RFS on subsequent anticancer therapy (RFS2). An IDMC will be commissioned for Cohort 1. Exploratory endpoints: Cohort 2- complete response (CR) rate at 6 months; Cohort 3- CR in marker lesion. Patients will be enrolled at sites in ~14 countries. EudraCT: 2019-002449-39. Loriot Y et al. N Engl J Med. 2019;381:338-48. Clinical trial information: 2019-002449-39.

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