scholarly journals Clinical Utility of Bladder Cancer Biomarkers

2020 ◽  
Vol 1 (1) ◽  
pp. 62-67
Author(s):  
Laura-Maria Krabbe ◽  
Georgios Gakis ◽  
Yair Lotan
Keyword(s):  
Bladder Cancer ◽  
Cancer Diagnosis ◽  
Local Treatment ◽  
Predictive Biomarkers ◽  
Patient Comfort ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Therapeutic Success ◽  
Muscle Invasive ◽  
Work Up

Each year, there are an estimated 550 000 diagnoses of bladder cancer worldwide, and almost 200 000 deaths from bladder cancer. The need for frequent follow-up, including invasive procedures like cystoscopy, repetitive procedures like transurethral resection of bladder tumors and intravesical instillation therapy in non-muscle invasive stages, as well as systemic treatment with or without radical local treatment in advanced stages, makes bladder cancer one of the most expensive cancers to treat. Prognostic and predictive biomarkers have the potential to fundamentally change bladder cancer treatment algorithms, which may result in improved patient comfort and oncological outcomes and may also decrease the socioeconomic burden of the disease. Intense research has resulted in the recent approval by the U. S. Food and Drug Administration of the first agent for this disease that targets a specific mutation (fibroblast-growth factor receptor). Yet, many areas of bladder cancer diagnosis and treatment have remained unchanged for decades, and this is only in part due to their therapeutic success. In order to integrate biomarkers into clinical practice patterns, specific considerations for the different disease stages and settings should be kept in mind. Especially in the setting of screening, work-up of hematuria, as well as surveillance of patients with non-muscle invasive bladder cancer, (urine-)biomarkers may prove useful. They must, however, demonstrate a high enough sensitivity to pick up a cancer diagnosis or recurrence, allow easy handling (preferably a point-of-care setting) and adequate cost–benefit relationships, while also providing additional information to a full work-up. A biomarker to identify patients with muscle invasive bladder cancer who are in need of—and likely to respond to—neoadjuvant therapy would be very useful. In later disease, early detection of recurrence or progression, as well as biomarkers guiding treatment decisions between the available systemic agents, will be paramount for improved patient care.

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 Application of nanotechnology in the diagnosis and treatment of bladder cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yadong Xu ◽  
Cheng Luo ◽  
Jieqiong Wang ◽  
Lingwu Chen ◽  
Junxing Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Diagnosis ◽  
Targeted Delivery ◽  
Complete Removal ◽  
Diagnosis And Treatment ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cancer Management ◽  
Sample Test ◽  
Muscle Invasive

AbstractBladder cancer (BC) is a common malignancy in the genitourinary system and the current theranostic approaches are unsatisfactory. Sensitivity and specificity of current diagnosis methods are not ideal and high recurrence and progression rates after initial treatment indicate the urgent need for management improvements in clinic. Nanotechnology has been proposed as an effective method to improve theranosis efficiency for both non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). For example, gold nanoparticles (AuNPs) have been developed for simple, fast and sensitive urinary sample test for bladder cancer diagnosis. Nanoparticles targeting bladder cancers can facilitate to distinguish the normal and abnormal bladder tissues during cystoscopy and thus help with the complete removal of malignant lesions. Both intravenous and intravesical agents can be modified by nanotechnology for targeted delivery, high anti-tumor efficiency and excellent tolerability, exhibiting encouraging potential in bladder cancer treatment. Photosensitizers and biological agents can also be delivered by nanotechnology, intermediating phototherapy and targeted therapy. The management of bladder cancer remained almost unchanged for decades with unsatisfactory effect. However, it is likely to change with the fast-developed nanotechnology. Herein we summarized the current utility of nanotechnology in bladder cancer diagnosis and treatment, providing insights for the future designing and discovering novel nanoparticles for bladder cancer management. Graphical Abstract

scholarly journals Moving towards Personalized Medicine in Muscle-Invasive Bladder Cancer: Where Are We Now and Where Are We Going?

2020 ◽  
Vol 21 (17) ◽  
pp. 6271 ◽  
Author(s):  
Juan Carlos Pardo ◽  
Vicenç Ruiz de Porras ◽  
Andrea Plaja ◽  
Cristina Carrato ◽  
Olatz Etxaniz ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Predictive Biomarkers ◽  
Conclusive Evidence ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Level Of Evidence ◽  
Recommended Treatment ◽  
Appropriate Treatment ◽  
Muscle Invasive ◽  
The Impact

Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the recommended treatment, with the highest level of evidence, for patients with muscle-invasive bladder cancer (MIBC). However, only a minority of patients receive this treatment, mainly due to patient comorbidities, the relatively small survival benefit, and the lack of predictive biomarkers to select those patients most likely to benefit from this multimodal approach. In addition, adjuvant chemotherapy has been recommended for patients with high-risk MIBC, although randomized trials have not provided conclusive evidence on the impact of this approach. At present, however, this situation is changing, largely due to our improved knowledge of the molecular biology of bladder cancer, which has enabled us to identify new prognostic and predictive biomarkers that can be used to select the most appropriate treatment for each patient. Moreover, new active treatments, especially immunotherapy, have shown promising results in the neoadjuvant setting. In addition, the gene expression profile of bladder tumors can be used to classify them into different subtypes, which correlate with specific clinical-pathological characteristics and with treatment response or resistance. Therefore, the main objective for the near future is to introduce these translational breakthroughs into routine clinical practice in order to personalize treatment for each patient.

scholarly journals Predictors of referral for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer and changes in practice over time

2015 ◽  
Vol 9 (7-8) ◽  
pp. 236 ◽  
Author(s):  
Geoffrey T. Gotto ◽  
Melissa Shea-Budgell ◽  
M. Sarah Rose ◽  
J. Dean Ruether
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Local Treatment ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Curative Therapy ◽  
Kaplan Meier ◽  
Muscle Invasive ◽  
Over Time

Introduction: In patients with non-metastatic muscle-invasive bladder cancer (MIBC) fit for curative therapy, a multidisciplinary approach consisting is recommended. This approach includes local treatment (usually radical cystectomy), ideally combined with neoadjuvant chemotherapy (NACT). Despite a survival benefit with NACT, uptake remains low. We assessed NACT consultation in Alberta and examined associative factors, as well as the relationship to survival.Methods: Patients with MIBC were identified through the Alberta Cancer Registry. Demographic and clinicopathologic information was collected from electronic medical records between 2007 and 2011. In addition to descriptive statistics, logistic regression was used to determine factors associated with receiving NACT consultation. Overall survival was described using a Kaplan-Meier estimate.Results: Of the 315 radical cystectomy patients, 140 (45.1%, 95% confidence interval [CI] 39.5, 50.8) received NACT consultation. Patients ≥80 years (odds ratio [OR] 0.21, 95% CI 0.08, 0.57, p = 0.002) and those treated in Calgary (OR 0.11, 95% CI 0.05, 0.25, p < 0.001) were less likely to receive NACT consultation. The rate of NACT consultation increased steadily from 2007 to 2011 (OR 1.23, 95% CI 1.04, 1.45 per year of diagnosis, p = 0.018). After a median follow-up of 28.1 months (range: 14.6–50.3), median survival was 54.7 months for patients who received NACT consultation versus 31.2 months for those who did not (p = 0.030).Conclusions: NACT consultation in patients with MIBC undergoing radical cystectomy has improved over time; however, regional differences underscore the need for a standardized approach to NACT consultation, including common referral mechanisms.

scholarly journals The consensus molecular classification of muscle-invasive bladder cancer

2018 ◽  
Author(s):  
Aurélie Kamoun ◽  
Aurélien de Reyniès ◽  
Yves Allory ◽  
Gottfrid Sjödahl ◽  
A. Gordon Robertson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Stromal Cells ◽  
Molecular Subtypes ◽  
Predictive Biomarkers ◽  
Molecular Classification ◽  
Classification Systems ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

AbstractMuscle-Invasive Bladder Cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, yielding diverse sets of subtypes, which hampers the clinical implications of such knowledge. Here, we report the results of a large international effort to reach a consensus on MIBC molecular subtypes. Using 1750 MIBC transcriptomes and a network-based analysis of six independent MIBC classification systems, we identified a consensus set of six molecular classes: Luminal Papillary (24%), Luminal Non-Specified (8%), Luminal Unstable (15%), Stroma-rich (15%), Basal/Squamous (35%), and Neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics. This consensus system offers a robust framework that will enable testing and validating predictive biomarkers in future clinical trials.

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