Prospective evaluation of a preoperative biomarker panel for prediction of upstaging at radical cystectomy

Shariat, Shahrokh F.; Passoni, Niccolò; Bagrodia, Aditya; Rachakonda, Varun; Xylinas, Évanguelos; Robinson, Brian D.; Kapur, Payal; Sagalowsky, Arthur I.; Lotan, Yair

doi:10.1111/bju.12343

Cited by 39 publications

(18 citation statements)

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“…p21 immunoreactivity was considered altered when samples had ≤10% staining [11]. Ki67 staining was considered to be altered when samples had >20% reactivity [12] [13] [14].…”

Section: Methodsmentioning

confidence: 99%

Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity

et al. 2014

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PurposeTo investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer.Materials and MethodsPatients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied.ResultsMuscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018).ConclusionADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.

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“…p21 immunoreactivity was considered altered when samples had ≤10% staining [11]. Ki67 staining was considered to be altered when samples had >20% reactivity [12] [13] [14].…”

Section: Methodsmentioning

confidence: 99%

Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity

et al. 2014

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“…Although the ‘gold standard’ treatment for muscle‐invasive bladder cancer (MIBC) remains radical cystectomy (RC), life expectancy after RC remains only 58% at 5 years . More accurate prognostication models and new therapeutic strategies are therefore under investigation to improve survival and follow‐up schemes in the field of bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

Comparing long‐term outcomes of primary and progressive carcinoma invading bladder muscle after radical cystectomy

et al. 2015

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ObjectiveTo assess the impact of primary or progressive status on recurrence-free survival (RFS), cancer-specific mortality (CSM) and overall mortality (OM) after radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). Patients and MethodsA total of 768 consecutive patients underwent RC as treatment for MIBC at our institution between 2000 and 2012. Primary MIBC was defined as no previous history of bladder cancer and progressive was defined as recorded previous treated non-MIBC (NMIBC) that had progressed to MIBC. The median follow-up was 85 (60-109) months. Univariate and multivariate Cox regression models were used to compare RFS, CSM and OM between these two cohorts. ResultsIn all, 475 (61.8%) patients had primary and 293 (38.2%) patients had progressive MIBC. There were no differences between the two groups in terms of demographics, pathological and peri-operative complications (all P > 0.1).The 10-year RFS, CSM and OM rates for primary vs progressive status were 43 vs 36% (P = 0.01), 43 vs 37% (P = 0.01), and 35 vs 28% (P = 0.03), respectively. On multivariable Cox regression analyses, progressive status remained significantly associated with a higher rate of recurrence (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.12-1.79; P = 0.03), CSM (HR 1.42, 95% CI 1.07-1.89; P = 0.01) and OM (HR1.42, 95% CI 1.13-1.65; P = 0.02). ConclusionsAmong patients treated with RC for MIBC, progressive status was associated with a higher CSM, OM and recurrence rate after RC. The present study thus provides an impetus to improve risk sub-stratification when bladder cancer is still at the NMIBC stage, be it through new biomarkers or improved imaging, as a subset of patients with NMIBC are likely to benefit from early RC.

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“…Urinary or circulating biomarkers represent a potential area of interest for the early detection and surveillance of bladder carcinoma due to the high accessibility of samples. Multiple tumor biomarkers have been investigated in this capacity, with variable results (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of MMP-2, MMP-9, TIMP-1, TIMP-2, NGAL and MMP-9/NGAL complex in urine and sera from patients with bladder cancer

Ricci¹,

Bruzzese²,

Carlo³

2015

Oncology Letters

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Abstract. The identification of biomarkers in urine or serum samples from patients with bladder cancer is urgently required for the development of non-invasive methods for the diagnosis of bladder carcinoma and to facilitate follow-up surveillance, to combat the high progression and recurrence rates of this type of cancer. The current study measured the content of matrix metalloproteinase (MMP)-2 and -9, as well as tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in the urine and sera of 41 patients with bladder cancer by ELISA. The association between levels of MMP-2 and -9 and TIMP-1 and -2, and tumor grade and stage were investigated to verify whether these molecules are involved in tumor differentiation. Statistical analysis of the data revealed that urinary TIMP-1 levels were significantly higher in the high grade group compared with those of the low grade samples (P=0.022). The results also revealed a significantly differing distribution of TIMP-1 expression between Ta and T1 stage specimens (P=0.040). The corresponding area under the curves (AUCs) were 0.72, with a sensitivity of 0.70 and specificity of 0.75. In addition, neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL complex levels in the sera were measured. All molecules evaluated were detected in the sera of the patients studied. In particular, tumors staged as non-muscle invasive (Ta and T1), demonstrated significantly higher NGAL levels compared with those of muscle invasive (>T1) bladder cancer (32.8 ng/ml vs. 16.2 ng/ml; P=0.029). The discriminatory ability of NGAL expression was confirmed by receiver operating characteristic curve analysis that revealed an AUC of 0.75, a sensitivity of 0.88 and a specificity of 0.67. These data indicated that urinary TIMP-1 and serum NGAL may be useful non-invasive biomarkers to provide clinical information for bladder cancer disease management. Multicenter, prospective studies are required to confirm these preliminary results. IntroductionBladder cancer (BCa) is one of the most common urologic malignancies worldwide; with a higher frequency amongst males than females (1). The two major environmental risk factors for BCa are high exposure to tobacco smoke, and occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons and chlorinated hydrocarbons (2,3). Furthermore, exposure to ionizing radiation, a variety of lifestyle choices, occupations, dietary factors, drugs, urologic pathologies, family history and genetic polymorphisms may increase the risk of bladder carcinoma (1-3). There are two clinical phenotypes of bladder carcinoma: Non-invasive and invasive BCa. Non-invasive BCa includes the papillary carcinoma phenotype (Ta) and flat carcinoma in situ (cis). Ta bladder carcinoma is superficial and rarely invades the basement membrane or metastasizes, but is associated with a high risk of local recurrence; while invasive bladder carcinoma has a high risk of disease progression, including muscle invasion and metastasis, and mortality. Ta tumorigenesis typically occurs via a mol...

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Prospective evaluation of a preoperative biomarker panel for prediction of upstaging at radical cystectomy

Cited by 39 publications

References 43 publications

Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity

Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity

Comparing long‐term outcomes of primary and progressive carcinoma invading bladder muscle after radical cystectomy

Evaluation of MMP-2, MMP-9, TIMP-1, TIMP-2, NGAL and MMP-9/NGAL complex in urine and sera from patients with bladder cancer

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