scholarly journals LINC00857 expression predicts and mediates the response to platinum-based chemotherapy in muscle-invasive bladder cancer

2018 ◽  
Vol 7 (7) ◽  
pp. 3342-3350 ◽  
Author(s):  
Aleksandra M. Dudek ◽  
Jasmijn G. M. van Kampen ◽  
J. Alfred Witjes ◽  
Lambertus A. L. M. Kiemeney ◽  
Gerald W. Verhaegh
Keyword(s):  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

scholarly journals Neoadjuvant Platinum-Based Chemotherapy is an Independent Predictor for Preoperative Thromboembolic Events in Bladder Cancer Patients Undergoing Radical Cystectomy

2016 ◽  
Vol 10 (3) ◽  
pp. 132-135 ◽  
Author(s):  
Cliodhna Browne ◽  
Niall F. Davis ◽  
William J. Nolan ◽  
Eoin D. MacCraith ◽  
Gerald M. Lennon ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Independent Predictor ◽  
Multivariate Regression Analysis ◽  
Invasive Bladder Cancer ◽  
Thromboembolic Events ◽  
Muscle Invasive Bladder Cancer ◽  
Cancer Group ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

Introduction: Neoadjuvant chemotherapy (NAC) confers a significant survival benefit in patients with muscle invasive bladder cancer. Platinum-based chemotherapy increases the risk of thromboembolic events (TEE). We determined the effect of cisplatin-based NAC on the incidence of preoperative TEEs in radical cystectomy patients. Materials and Methods: A retrospective matched case-control study was performed on 55 patients undergoing radical cystectomy for muscle invasive bladder cancer. Group 1 (n = 20) included patients that received NAC prior to radical cystectomy and Group 2 (n = 35) included patients that underwent radical cystectomy without NAC. Logistic regression analyses tested potential predictors for TEEs in both groups (age, American Society of Anesthesiologists grade, use of NAC, histological subtype, pathological stage). Results: In total, 6 patients of 55 developed a TEE. Five patients of 20 (25%) treated with NAC prior to radical cystectomy developed TEEs, while 1 of 35 (2.9%) treated with radical cystectomy alone developed a TEE. On univariate and multivariate regression analysis, NAC prior to radical cystectomy was an independent predictor for TEE prior to radical cystectomy (p = 0.033 and p = 0.043, respectively). The effect of perioperative anticoagulation on operative blood loss and postoperative hemoglobin level was not statistically significant between both groups (p = 0.22 and p = 0.08, respectively). Conclusion: Neoadjuvant cisplatin-based chemotherapy is a significant predictor for preoperative TEE in patients undergoing radical cystectomy.

JUND-dependent up-regulation of HMOX1 is associated with cisplatin resistance in muscle-invasive bladder cancer

2020 ◽  
Vol 168 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Ye Peng ◽  
Yongjie Chen ◽  
Shiwei Chen ◽  
Jiaolian Wang ◽  
Cheng Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Acquired Resistance ◽  
Genetically Engineered ◽  
Invasive Bladder Cancer ◽  
Clinical Samples ◽  
Heme Oxygenase 1 ◽  
Muscle Invasive Bladder Cancer ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

Abstract The standard-of-care for metastatic muscle-invasive bladder cancer (MIBC) is platinum-based chemotherapy regimens. Acquired resistance that occurs frequently through unidentified mechanisms, however, remains the major obstacle for implementing therapeutic effectiveness. Here, using data mining and analysis on clinical samples, we show that expression of JUND, a core component of activator protein-1 family, was significantly induced in cisplatin (CDDP)-resistant MIBC. Accumulation of nuclear JUND was associated with low post-chemotherapy survival in MIBC patients. In both genetically engineered cell models and murine xenograft models, we provided evidence that bladder cancer (BC) cells with excessive JUND expression were less responsive to CDDP treatment. This CDDP resistance was further demonstrated to be mediated, at least in part, by transactivation of HMOX1 [the gene encoding heme oxygenase-1 (HO-1)], one of the most important antioxidant signalling pathways of cell adaptation to stress. One mutation within the HMOX1 promoter successfully abolished oxidative stress-enhanced and JUND-driven HMOX1 promoter activation, suggesting that this unique site synergized for maximal HO-1 induction in CDDP-challenged BC cells. Overall, our data highlight an indispensible role of JUND, both as a target as a modifier of the oxidative stress signalling, in conferring an adaptive response during the pathogenesis of CDDP resistance in MIBC.

Durvalumab as neoadjuvant therapy for muscle-invasive bladder cancer: Preliminary results from the Bladder Cancer Signal Seeking Trial (BLASST)-2.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 507-507 ◽  
Author(s):  
Xiao X. Wei ◽  
Bradley Alexander McGregor ◽  
Richard J. Lee ◽  
Xin Gao ◽  
Kerry L. Kilbridge ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Therapy ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Predictive Biomarkers ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

507 Background: There is no established neoadjuvant therapy (NAT) for patients (pt) with muscle invasive bladder cancer (MIBC) ineligible for cisplatin-based chemotherapy preceding radical cystectomy. Encouraging prospective data indicate PD-1/PD-L1 inhibitors, including pembrolizumab and atezolizumab, are safe and active as NAT for MIBC. Durvalumab (D), a PD-L1 inhibitor, is FDA approved for treating locally advanced or metastatic urothelial carcinoma following platinum-based chemotherapy. The safety and activity of D as NAT in MIBC have not been reported. Methods: We are conducting a single-center sequential multicohort trial (NCT03773666) of D alone (Cohort 1, N=10) and D plus the CD73 inhibitor oleclumab (Cohort 2, N=10) in cT2-T4aN0M0 MIBC pts who are RC candidates and are ineligible for or declined cisplatin-based chemotherapy. The primary endpoint is feasibility, defined as ≥7 of 10 pts receiving at least 1 dose of D followed by radical cystectomy without dose limiting toxicity (DLT) up to 12 wks post-RC. In Cohort 1, D is administered at 750mg IV Q2W for 3 cycles followed by RC 2-4 weeks after the last dose. Baseline and RC tissue and baseline and on-study blood are collected for correlative studies, including immunohistochemistry, genomics, transcriptomics, and metabolomics. Results: Cohort 1 has completed enrollment; ten pts were enrolled between Feb 2019 to Sept 2019. Median age was 67 (Range: 53-85) and 8 (80%) were men. All 10 pts completed 3 durvalumab doses. Eight pts completed planned RC with at least 12wk follow-up post-op to date. No DLTs were observed. One Grade 3 treatment-related adverse event (trAE) was reported (anemia), with no Grade 4 or higher trAE. Pathologic response (<pT2N0) was seen in 2 of 8 (25%) pts with pathologic complete response (pT0) in 1 (12.5%) pts. Updated safety and efficacy data from Cohort 1 will be presented. Conclusions: D appears to be feasible as NAT in MIBC with preliminary evidence for antitumor activity. Toxicities are consistent with data from other PD-1/PD-L1 inhibitor trials. Future cohorts will examine D-containing combination NAT strategies. Analysis of tissue and blood-based predictive biomarkers are ongoing. Clinical trial information: NCT03773666.

scholarly journals Changes in Lean Muscle Mass Associated with Neoadjuvant Platinum-Based Chemotherapy in Patients with Muscle Invasive Bladder Cancer

2018 ◽  
Vol 4 (4) ◽  
pp. 411-418 ◽  
Author(s):  
Kalen J. Rimar ◽  
Alexander P. Glaser ◽  
Shilajit Kundu ◽  
Edward M. Schaeffer ◽  
Joshua Meeks ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Muscle Mass ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Lean Muscle Mass ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

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.

scholarly journals Role of checkpoint inhibitors immunotherapy in non-muscle invasive bladder cancer: current methods and future perspectives

2021 ◽  
Vol 9 (3) ◽  
pp. 79-84
Author(s):  
Ayman Agag ◽  
Naufal Naushad ◽  
Asad Manzoor ◽  
Sami A Abbas ◽  
Abdalla Ali Deb ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
High Risk ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Oncological Results ◽  
Muscle Invasive

Immuno-therapy involvement in bladder urothelial malignancies is growing very fast. The use of Immuno-therapy with check-point inhibitor has greatly developed since it was first approved as a second-line treatment for cases who had formerly failed platinum-based chemotherapy. There are recognized applications for first-line metastatic illness in platinum-ineligible or cisplatin-ineligible PD-L1 diagnosed cases, as well as a label for BCG-refractory high-risky non-muscle invasive bladder cancer (NMIBC). It is now being studied in neo-adjuvant and adjuvant muscle invasive bladder cancer (MIBC) clinical trials. This review discusses the clinical trials that led to these FDA agreements, as well as prospective and ongoing trials. Current clinical guidelines support Bacillus Calmette-Guérin (BCG) as the primary treating option for intermediate to high-risk NMIBC. Despite the intra-vesical BCG-instillation, intra-vesical relapse occurs in a considerable number of individuals with intermediate to high risk NMIBC. Furthermore, treating BCG-nonresponsive NMIBC is still difficult. For these individuals with BCG-nonresponsive NMIBC, there are no viable therapy alternatives other than radical cystectomy, which has been shown to have excellent oncological results. In this regard, for the care of BCG-nonresponsive NMIBC, safe and reliable noninvasive or lesser-invasive therapeutic alternatives with adequate oncological results are needed. Regarding the latest introduction of immuno-therapeutic medications, the treatment of progressive or metastatic urothelial cancer has substantially advanced. These developments have sparked a surge in interest in immuno-therapeutic medications for NMIBC, particularly BCG-nonresponsive NMIBC. The goal of this literature review is to provide and debate the most up-to-date information on the function of Immuno-therapy in BCG-nonresponsive NMIBC and the presently accessible treatment options. Furthermore, this page highlights the current research in this topic. We wanted to convey the current state of Immuno-therapy in NMIBC and discuss future directions.

scholarly journals Contemporary best practice in the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer

2019 ◽  
Vol 11 ◽  
pp. 175628721882367 ◽  
Author(s):  
Gautier Marcq ◽  
Edouard Jarry ◽  
Idir Ouzaid ◽  
Jean-François Hermieu ◽  
François Henon ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Best Practice ◽  
Invasive Bladder Cancer ◽  
High Dose ◽  
Muscle Invasive Bladder Cancer ◽  
Oncological Outcomes ◽  
Platinum Based Chemotherapy ◽  
The Absolute ◽  
Muscle Invasive

Background: We aimed to provide a comprehensive literature review on the best practice management of patients with nonmetastatic muscle-invasive bladder cancer (MIBC) using neoadjuvant chemotherapy (NAC). Method: Between July and September 2018, we conducted a systematic review using MEDLINE and EMBASE electronic bibliographic databases. The search strategy included the following terms: Neoadjuvant Therapy and Urinary Bladder Neoplasms. Results: There is no benefit of a single-agent platinum-based chemotherapy. Platinum-based NAC is the gold standard therapy and mainly consists of a combination of cisplatin, vinblastine, methotrexate, doxorubicin, gemcitabine or even epirubicin (MVAC). At 5 years, the absolute overall survival benefit of MVAC was 5% and the absolute disease-free survival was improved by 9%. This effect was observed independently of the type of local treatment and did not vary between subgroups of patients. Moreover, a ypT0 stage (complete pathological response) after radical cystectomy was a surrogate marker for improved oncological outcomes. High-density MVAC has been shown to decrease toxicity (with a grade 3–4 toxicity ranging from 0% to 26%) without impacting oncological outcomes. To date, there is no role for carboplatin administration in the neoadjuvant setting in patients that are unfit for cisplatin-based NAC administration. So far, there is no published trial evaluating the role of immunotherapy in a neoadjuvant setting, but many promising studies are ongoing. Conclusion: There is a strong level of evidence supporting the clinical use of a high-dose-intensity combination of methotrexate, vinblastine, doxorubicin and cisplatin in a neoadjuvant setting. The landscape of MIBC therapies should evolve in the near future with emerging immunotherapies.

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