Progression to T1 High Grade (T1HG) from a Lower Stage/Grade is Associated with Poorer Survival Outcomes than Initial Diagnosis with T1HG Bladder Cancer

2017 ◽  
Vol 24 (8) ◽  
pp. 2413-2419 ◽  
Author(s):  
Jung Kwon Kim ◽  
Chang Wook Jeong ◽  
Cheol Kwak ◽  
Hyun Hoe Kim ◽  
Ja Hyeon Ku
Keyword(s):  
Bladder Cancer ◽  
Initial Diagnosis ◽  
Survival Outcomes ◽  
High Grade ◽  
Lower Stage

scholarly journals Survival Outcomes of Early versus Deferred Cystectomy for High-Grade Non-Muscle-Invasive Bladder Cancer: A Systematic Review

2020 ◽  
Vol 14 (2) ◽  
pp. 66-73
Author(s):  
Jonathan C. M. Wan
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Treatment Plan ◽  
Invasive Bladder Cancer ◽  
Survival Outcomes ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Term Survival ◽  
Muscle Invasive

Background: Studies report that survival outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) are worse when cystectomy is delayed. However, no systematic evidence is available. Objective: The aim of this study was to systematically review the literature to compare the long-term survival outcomes of patients with high-grade NMIBC (T1G3, including carcinoma in situ) who have early cystectomy compared to deferred radical cystectomy post-diagnosis. Materials and Methods: A systematic review was carried out by searching MEDLINE and related databases (Google Scholar, National Health Service Evidence) for all relevant studies published from 1946 to present. Additional studies were identified through following the references of relevant papers. Studies were included if they met the following criteria: inclusion of at least 30 patients having high-grade NMIBC, 2 groups treated with either early or deferred cystectomy with a clear temporal cut-off between groups and reported data on survival rate of at least 5 years. Results: Literature was systematically reviewed, and 10 studies were included, totaling 1,516 patients who underwent either primary cystectomy or deferred cystectomy. It was found that patients who underwent early cystectomy show improved 5- to 10-year cancer-specific survival (relative risk = 0.81, p = 0.029) suggesting a significant survival benefit when compared to deferred cystectomy. Conclusions: This study provides systematically gathered evidence showing benefit of early cystectomy. Despite this result, radical cystectomy greatly impairs quality of life and represents overtreatment for a significant minority. This result highlights the importance of a decisive treatment plan to minimize treatment delay.

scholarly journals Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Scott J. Weir ◽  
Prasad Dandawate ◽  
David Standing ◽  
Sangita Bhattacharyya ◽  
Prabhu Ramamoorthy ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Urothelial Cancer ◽  
Phase 1 ◽  
Intraperitoneal Administration ◽  
Presenilin 1 ◽  
Proliferation Index ◽  
High Grade ◽  
Lower Stage

AbstractCiclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and hematologic malignancies. Its clinical utility as an oral anticancer agent, however, is limited by poor oral bioavailability and gastrointestinal toxicity. Fosciclopirox, the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration. We characterized the activity of CPX-POM and its major metabolites in in vitro and in vivo preclinical models of high-grade urothelial cancer. CPX inhibited cell proliferation, clonogenicity and spheroid formation, and increased cell cycle arrest at S and G0/G1 phases. Mechanistically, CPX suppressed activation of Notch signaling. Molecular modeling and cellular thermal shift assays demonstrated CPX binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. To establish in vivo preclinical proof of principle, we tested fosciclopirox in the validated N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) mouse bladder cancer model. Once-daily intraperitoneal administration of CPX-POM for four weeks at doses of 235 mg/kg and 470 mg/kg significantly decreased bladder weight, a surrogate for tumor volume, and resulted in a migration to lower stage tumors in CPX-POM treated animals. This was coupled with a reduction in the proliferation index. Additionally, there was a reduction in Presenilin 1 and Hes-1 expression in the bladder tissues of CPX-POM treated animals. Following the completion of the first-in-human Phase 1 trial (NCT03348514), the pharmacologic activity of fosciclopirox is currently being characterized in a Phase 1 expansion cohort study of muscle-invasive bladder cancer patients scheduled for cystectomy (NCT04608045) as well as a Phase 2 trial of newly diagnosed and recurrent urothelial cancer patients scheduled for transurethral resection of bladder tumors (NCT04525131).

Bladder sparing surgery in high-grade bladder cancer

2019 ◽  
Vol 41 (2) ◽  
Author(s):  
P.G Yakovlev.* ◽  
◽  
D.A. Klyushin ◽  
R.I. Vereshchako ◽  
◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Grade ◽  
Bladder Sparing

scholarly journals Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer

2021 ◽  
Author(s):  
David D’Andrea ◽  
Peter C. Black ◽  
Homayoun Zargar ◽  
Kamran Zargar-Shoshtari ◽  
Francesco Soria ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Preoperative Chemotherapy ◽  
Objective Response ◽  
Pathologic Complete Response ◽  
Invasive Bladder Cancer ◽  
Survival Outcomes ◽  
Muscle Invasive Bladder Cancer ◽  
Patient Age ◽  
Patient Âgé ◽  
Muscle Invasive

Abstract Purpose To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). Materials and methods We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. Results pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6–37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. Conclusions While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Survival outcomes according to salvage treatments for local bladder cancer recurrences following radical cystectomy

2019 ◽  
Vol 18 (9) ◽  
pp. e3204-e3205
Author(s):  
M. Colicchia ◽  
M. Soligo ◽  
A. Morlacco ◽  
A. Pellizzari ◽  
L. Boeri ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Survival Outcomes
Sign in / Sign up

Export Citation Format

Share Document