scholarly journals ANLN and TLE2 in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1840 ◽  
Author(s):  
Sheng Wu ◽  
Katja Nitschke ◽  
Jakob Heinkele ◽  
Cleo-Aron Weis ◽  
Thomas Stefan Worst ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
In Silico ◽  
Disease Free Survival ◽  
Actin Binding ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
The Impact

Anilin actin binding protein (ANLN) and transducing-like enhancer protein 2 (TLE2) are associated with cancer patient survival and progression. The impact of their gene expression on progression-free survival (PFS) of patients with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) and subtype association has not yet been investigated. qRT-PCR was used to measure the transcript levels of ANLN and TLE2 in the Mannheim cohort, and validated in silico by The Cancer Genome Atlas (TCGA) cohort. Uni- and multivariate Cox regression analyses identified predictors for disease-specific survival (DSS) and overall survival (OS). In the Mannheim cohort, tumors with high ANLN expression were associated with lower OS and DSS, while high TLE2 expression was associated with a favorable OS. The TCGA cohort confirmed that high ANLN and low TLE2 expression was associated with shorter OS and disease-free survival (DFS). In both cohorts, multivariate analyses showed ANLN and TLE2 expression as independent outcome predictors. Furthermore, ANLN was more highly expressed in cell lines and patients with the basal subtype, while TLE2 expression was higher in cell lines and patients with the luminal subtype. ANLN and TLE2 are promising biomarkers for individualized bladder cancer therapy including cancer subclassification and informed MIBC prognosis.

Effectiveness and safety of valrubicin in non–muscle-invasive bladder cancer following reintroduction: Results from a medical chart review study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 296-296
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Concomitant Medication ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
The United States ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

296 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report secondary outcomes and concomitant medication use from a US multicenter, observational, retrospective study. Methods: Medical records of adult patients with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted (March–September 2011). Kaplan-Meier analyses were performed for disease-free survival (DFS), progression-free survival (PFS), worsening-free survival (WFS), cystectomy-free survival (CFS), and time to cystectomy. Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 instillations [range, 2–18]). 107 patients (94.7%) received >3 instillations; 97 (85.8%) completed the full course of therapy (≥6 instillations). DFS was 51.6% (95% CI, 40.9%–61.3%) at 3 months, 30.4% (95% CI, 20.4%–41.1%) at 6 months, and median DFS was 3.5 months (95% CI, 2.5–4.0). PFS was 97.6% (95% CI, 90.9%–99.4%) at 3 months, 87.2% (95% CI, 75.4%–93.5%) at 6 months, and median PFS was 18.2 months (95% CI, 17.2–19.0). WFS was 47.4% (95% CI, 37.2%–57.0%) at 3 months and 28.1% (95% CI, 18.8%–38.2%) at 6 months. CFS was 98.0% (95% CI, 92.2%–99.5%) at 3 months and 93.7% (95% CI, 85.2%–97.4%) at 6 months. Median CFS was not reached; only 13.3% of patients underwent radical cystectomy after starting valrubicin. 56 patients (49.6%) experienced ≥1 local adverse reaction; the most common were hematuria and pollakiuria (both 17.7%), micturition urgency (15.9%), and bladder spasm (14.2%). 55 patients (48.7%) used ≥1 concomitant medication for local adverse reactions; the most commonly used were urinary antispasmodics (21.2%), fluoroquinolones (14.2%), and other urologicals (14.2%). Conclusions: In patients with NMIBC treated with intravesical valrubicin, median DFS and PFS were 3.5 and 18.2 months, respectively, and median CFS was not reached as only 13% of patients underwent radical cystectomy. Valrubicin was well tolerated, and most patients received the full course of 6 instillations. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc.

Feasibility and efficacy of gemcitabine and carboplatin neoadjuvant chemotherapy in muscle-invasive bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16100-e16100
Author(s):  
T. Koie ◽  
H. Yamamoto ◽  
A. Okamoto ◽  
S. Hatakeyama ◽  
A. Momose ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Objective Response ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
Disease Free

e16100 Background: The neoadjuvant M-VAC followed by radical cystectomy for muscle-invasive bladder cancer has improved survival compared to radical cystectomy alone. Nevertheless, M-VAC has been associated with severe toxicity. The objective of this retrospective study was to evaluate the objective response rate, the impact on overall survival, disease-free survival, disease-free survival and toxicity adverse events of gemcitabine and carboplatin (GC) neoadjuvant chemotherapy in patients with locally advanced bladder cancer. Methods: We reviewed the clinical and pathological data of 140 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for T2N0M0 to T4aN0M0 bladder cancer at our institution between January 2001 and August 2008. Seventy patients were treated with neoadjuvant GC followed by cystectomy between March 2005 and August 2008 (GC group), and 70 patients were treated with cystectomy alone between January 2001 and May 2007 (cystectomy alone group). In the GC group, the patients received 2 courses of GC therapy consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, cancer-specific survival, disease free survival, and toxicity. Results: Fifteen patients (23.8%) had a complete response and 26 patients (41.3%) had a partial response in the GC group. At a mean follow-up period of 26.7 months, the overall survival was 85.0% in the GC group and 47.8% in the cystectomy alone group (p = 0.003). The cancer-specific survival was 78.4% in the GC group and 44.6% in the cystectomy alone group (p = 0.0018). The disease-free survival was 82.9% in the GC group and 35.7% in the cystectomy alone group (p = 0.0001). Hematologic toxicities were the main adverse events. Grade 3/4 neutropenia occurred in 26 patients (37.1%) and thrombocytopenia in 15 (21.4%). There was no grade 3/4 gastrointestinal toxicity and no renal function abnormalities. Conclusions: Although this is not a randomized study, the GC neoadjuvant therapy followed by radical cystectomy is feasible and may be associated with improved survival among patients with muscle-invasive bladder cancer. A randomized trial is warranted. No significant financial relationships to disclose.

scholarly journals Construction of an Immune-Associated Gene-Based Signature in Muscle-Invasive Bladder Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Chengquan Shen ◽  
Ting Xu ◽  
Yefeng Sun ◽  
Liping Wang ◽  
Zhijuan Liang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Survival Analysis ◽  
Risk Score ◽  
Disease Free Survival ◽  
Differentially Expressed ◽  
Invasive Bladder Cancer ◽  
Prognostic Signature ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

Background. In recent years, immune-associated genes (IAGs) have been documented as having critical roles in the occurrence and progression of muscle-invasive bladder cancer (MIBC). Novel immune-related biomarkers and a robust prognostic signature for MIBC patients are still limited. The study is aimed at developing an IAG-based signature to predict the prognosis of MIBC patients. Methods. In the present study, we identified differentially expressed IAGs in MIBC by using transcriptomics data from The Cancer Genome Atlas (TCGA) database and proteomics data from our samples. We further constructed an IAG-based signature and evaluated its prognostic and predictive value by survival analysis and nomogram. Tumor Immune Estimation Resource (TIMER) was applied to explore the correlation between the IAG-based signature and immune cell infiltration in the microenvironment of MIBC. Results. A total of 22 differentially expressed IAGs were identified, and 2 IAGs (NR2F6 and AHNAK) were used to establish a prognostic signature. Subsequently, survival analysis showed that high-risk scores were significantly correlated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of MIBC patients. A prognostic nomogram was constructed by integrating clinical factors with the IAG-based signature risk score. In addition, the IAG-based signature risk score was positively associated with the infiltration of macrophages and dendritic cells in MIBC. Conclusions. We constructed and verified a novel IAG-based signature, which could predict the prognosis of MIBC and might reflect the status of the immune microenvironment of MIBC. Further studies in more independent clinical cohorts and further experimental exploration of the prognostic IAG-based signature are still needed.

Impact of sarcopenia for patients with localized muscle invasive bladder cancer treated by neoadjuvant cisplatin based chemotherapy and radical cystectomy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18286-e18286
Author(s):  
Emilien Billon ◽  
Pierre Regnier ◽  
Valeria De Luca ◽  
Serge Brunelle ◽  
Jochen Walz ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Skeletal Muscle Index ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive ◽  
The Impact

e18286 Background: Several studies suggested the prognostic importance of sarcopenia in survival or treatment complications in cancer. The concept of cancer prehabilitation before surgery is gaining wide recognition. The aim of our study was to assess the impact of sarcopenia on chemotherapy toxicities and survival in patients with localized muscle invasive bladder cancer (MIBC). Methods: Between January 2012 and December 2017, patients who underwent neoadjuvant platinum-based chemotherapy (NAC) followed by radical cystectomy (RC) for cT2-T4 N0 M0 MIBC were retrospectively selected, from a single institution cohort. Using CT scan: before NAC, after NAC and after cystectomy, sarcopenia was defined according to the Lumbar Skeletal Muscle Index (SMI) in L3 assessed by two observers blinded to patients’ status. Results: 82 patients were selected, 62 men (75.6%) and 20 women (24.4%), with a median age of 64.5 years (31 to 80). 35 were considered severe sarcopenic (SMI < 35cm2/m2 for women and SMI < 50 cm2/m2 for men) before NAC. The characteristics between severe and non-severe sarcopenic patients were not significantly different except for weight (71.7 vs 81.1kg, p = 0.006) and BMI (24.0 vs 28.4kg/m2, p = 8.0x10-6). Sarcopenia pre-chemotherapy was significantly associated with nausea (p = 0.003), hypokalemia (p = 0.023) and with platinum dose-intensity during NAC (p = 0.007) but was not significantly associated with overall survival (OS) or disease-free survival (DFS). Sarcopenia post-cystectomy was correlated with the OS (HR = 0.94, CI95% [0.89-0.99], p = 0.01), but not DFS. In multivariate analysis, factors associated with OS were post cystectomy sarcopenia (p = 0.038), pN status (p = 0.001) and glomerular filtration rate (p = 0.045). Conclusions: For localized MIBC, sarcopenic status before platinum based NAC could predict some chemotherapy toxicities. After radical cystectomy, sarcopenia is an independent prognostic factor for OS. Improve patients care by prehabilitation during NAC and before surgery, using physical, nutritional and psycho-social supports, could decrease chemotherapy toxicities and improve survival particularly for sarcopenic patients.

1057 POST-CHEMOTHERAPY AKR1B10 EXPRESSION CORRELATES WITH DISEASE FREE SURVIVAL IN MUSCLE-INVASIVE BLADDER CANCER

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Yasuhiro Hashimoto ◽  
Takuya Koie ◽  
Hayato Yamamoto ◽  
Atsushi Imai ◽  
Shingo Hatakeyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
Disease Free

The Role of Partial Cystectomy in the Treatment of Muscle-Invasive Bladder Cancer

2005 ◽  
Vol 72 (2) ◽  
pp. 215-223
Author(s):  
P. Tombolini ◽  
M. Ruoppolo ◽  
G. Dormia ◽  
E. Dormia
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Free Survival ◽  
Muscle Invasive ◽  
Bladder Sparing ◽  
Disease Free

Partial cystectomy has been widely performed in the treatment of muscle-invasive bladder cancer in the 1960s and 70s. During the 1970s and 80s a more aggressive surgical approach was advocated by urologists. However, major complications occurred in 4–25% of patients undergoing radical cystectomy and urinary diversion. The overall survival in patients managed by radical cystectomy has increased during the last decades, but disease-free survival remains the same. This procedure allows excellent loco-regional tumor control, but not changes in the timing of distant metastases and in the failure to control the disease. Recently, multimodal strategies in sparing bladder surgery have been proposed. Neoadjuvant chemotherapy, with or without irradiation, allows bladder sparing surgery in selected patients. A literature review demonstrates a later recurrence in the preserved bladder ranging from 40–75%. One-third of these recurrences required cystectomy and 15–20% of cases with bladder preservation experienced disease progression and died of cancer within 2 yrs. Only 40 and 20% of T2-T3 bladder cancer patients are alive and disease-free at 5 and 10 yrs of follow-up, respectively. In our experience, in selected patients, disease-free survival, overall survival, time to progression and final bladder preservation rate was higher compared to other patients. Bladder sparing in selected patients, i.e. single non-recurrent neoplasm, favorable site, no prostatic or urethral involvement, complete response to neoadjuvant chemotherapy, no P53 overexpression, no previous BCG-failure, is a feasible approach. Cystectomy, possibly with neobladder tailoring, is currently, the standard therapy for muscle-invasive bladder cancer. A better understanding of bladder tumor disease is necessary to choose the optimal treatment and to control each individual patient.

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