Guideline of guidelines: non‐muscle‐invasive bladder cancer

Woldu, Solomon L.; Bagrodia, Aditya; Lotan, Yair

doi:10.1111/bju.13760

Cited by 206 publications

(190 citation statements)

References 64 publications

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“…Although lowgrade bladder tumors rarely invade the bladder muscle and metastasize, high-grade tumors will become muscle invasive if not detected early (1,2). Non-muscle invasive bladder tumors are treated with transurethral tumor resection, and with additional intravesical therapy if the tumor is high-grade; however, frequent recurrence of the tumors in the bladder require regular surveillance and is associated with morbidity and medical cost (3,4). Patients with muscle invasive bladder cancer (MIBC) undergo cystectomy.…”

Section: Introductionmentioning

confidence: 99%

β-Arrestins Regulate Stem Cell-Like Phenotype and Response to Chemotherapy in Bladder Cancer

Kallifatidis

Smith

Morera

et al. 2019

Molecular Cancer Therapeutics

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b-Arrestins are classic attenuators of G-protein-coupled receptor signaling. However, they have multiple roles in cellular physiology, including carcinogenesis. This work shows for the first time that b-arrestins have prognostic significance for predicting metastasis and response to chemotherapy in bladder cancer. b-Arrestin-1 (ARRB1) and b-arrestin-2 (ARRB2) mRNA levels were measured by quantitative RT-PCR in two clinical specimen cohorts (n ¼ 63 and 43). The role of ARRBs in regulating a stem cell-like phenotype and response to chemotherapy treatments was investigated. The consequence of forced expression of ARRBs on tumor growth and response to Gemcitabine in vivo were investigated using bladder tumor xenografts in nude mice. ARRB1 levels were significantly elevated and ARRB2 levels downregulated in cancer tissues compared with normal tissues. In multivariate analysis only ARRB2 was an independent predictor of metastasis, diseasespecific-mortality, and failure to Gemcitabine þ Cisplatin (GþC) chemotherapy; $80% sensitivity and specificity to predict clinical outcome. ARRBs were found to regulate stem cell characteristics in bladder cancer cells. Depletion of ARRB2 resulted in increased cancer stem cell markers but ARRB2 overexpression reduced expression of stem cell markers (CD44, ALDH2, and BMI-1), and increased sensitivity toward Gemcitabine. Overexpression of ARRB2 resulted in reduced tumor growth and increased response to Gemcitabine in tumor xenografts. CRISPR-Cas9-mediated gene-knockout of ARRB1 resulted in the reversal of this aggressive phenotype. ARRBs regulate cancer stem cell-like properties in bladder cancer and are potential prognostic indicators for tumor progression and chemotherapy response.

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Section: Introductionmentioning

confidence: 99%

β-Arrestins Regulate Stem Cell-Like Phenotype and Response to Chemotherapy in Bladder Cancer

Kallifatidis

Smith

Morera

et al. 2019

Molecular Cancer Therapeutics

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“…The drugs doxorubicin hydrochloride, MMC and gemcitabine hydrochloride were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Tritium labelled DTX ( 3 H-DTX, specific activity 50.8 mCi/mmol), 3…”

Section: Methodsmentioning

confidence: 99%

Enhanced taxane uptake into bladder tissues following co‐administration with either mitomycin C, doxorubicin or gemcitabine: association to exfoliation processes

et al. 2018

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The exfoliation effects of MMC, doxorubicin and gemcitabine allow for good tissue penetration of these drugs with no additional effect from CNP treatment of bladders. The observed exfoliation effect of these amine-containing drugs probably arises from a cationic interaction with the mucus and urothelium cell layer in a manner similar to that previously reported for CNPs. These studies suggest that the lack of long-term clinical efficacy of these drugs may not arise from poor intravesical drug penetration but may result from a rapid diffusion of the drugs into the deeper vascularised muscular region with rapid drug clearance. The enhanced uptake of PTX or DTX following co-administration with MMC, doxorubicin or gemcitabine probably arises from the removal of the urothelial barrier by exfoliation allowing for improved taxane partitioning into superficial layers. These effects may allow for dual drug intravesical strategies offering greatly improved taxane uptake and potential additive drug effects for improved efficacy.

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“…While, the American Urological Association guidelines suggest to offer an initial RC to patients with persistent T1 HG/G3 on re-TUR, the European Association of Urology (EAU) guidelines does not give specific recommendations [14]. Indeed, the presence of T1 on re-TUR after the initial TUR showing T1 HG/G3 confers worse survival in singlecenter or multicenter heterogeneous datasets.…”

Section: Introductionmentioning

confidence: 99%

High-Grade T1 on Re-Transurethral Resection after Initial High-Grade T1 Confers Worse Oncological Outcomes: Results of a Multi-Institutional Study

et al. 2018

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Introduction: The aim of this multicenter study was to investigate the prognostic impact of residual T1 high-grade (HG)/G3 tumors at re-transurethral resection (TUR of bladder tumor) in a large multi-institutional cohort of patients with primary T1 HG/G3 bladder cancer (BC). Patients and Methods: The study period was from January 2002 to December 2012. A total of 1,046 patients with primary T1 HG/G3 and who had non-muscle invasive BC (NMIBC) on re-TUR followed by adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy with maintenance were included. Endpoints were time to disease recurrence, progression, and overall and cancer-specific death. Results: A total of 257 (24.6%) patients had residual T1 HG/G3 tumors. The presence of concomitant carcinoma in situ, multiple and large tumors (> 3 cm) at first TUR were associated with residual T1 HG/G3. Five-year recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were 17% (CI 11.8–23); 58.2% (CI 50.7–65); 73.7% (CI 66.3–79.7); and 84.5% (CI 77.8–89.3), respectively, in patients with residual T1 HG/G3, compared to 36.7% (CI 32.8–40.6); 71.4% (CI 67.3–75.2); 89.8% (CI 86.6–92.3); and 95.7% (CI 93.4–97.3), respectively, in patients with NMIBC other than T1 HG/G3 or T0 tumors. Residual T1 HG/G3 was independently associated with RFS, PFS, OS, and CSS in multivariable analyses. Conclusions: Residual T1 HG/G3 tumor at re-TUR confers worse prognosis in patients with primary T1 HG/G3 treated with maintenance BCG. Patients with residual T1 HG/G3 for primary T1 HG/G3 are very likely to fail BCG therapy alone.

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Guideline of guidelines: non‐muscle‐invasive bladder cancer

Cited by 206 publications

References 64 publications

β-Arrestins Regulate Stem Cell-Like Phenotype and Response to Chemotherapy in Bladder Cancer

β-Arrestins Regulate Stem Cell-Like Phenotype and Response to Chemotherapy in Bladder Cancer

Enhanced taxane uptake into bladder tissues following co‐administration with either mitomycin C, doxorubicin or gemcitabine: association to exfoliation processes

High-Grade T1 on Re-Transurethral Resection after Initial High-Grade T1 Confers Worse Oncological Outcomes: Results of a Multi-Institutional Study

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