Prognostic Markers in Bladder Cancer: A Contemporary Review of the Literature

Stein, John P.; Grossfeld, Gary D.; Ginsberg, David A.; Esrig, David; Freeman, John A.; Figueroa, Arsenio J.; Skinner, Donald G.; Côté, Richard J.

doi:10.1016/s0022-5347(01)62747-2

Cited by 237 publications

(130 citation statements)

References 148 publications

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“…4 Furthermore, the overall specificity is relatively low, partly because those proteins may be increased in urine of patients with non neoplastic diseases such as inflammatory conditions. 3 Furthermore, certain tests must be performed in specialized laboratories. For example, NMP22 (Matritech, Cambridge, MA) detects a nuclear mitotic apparatus protein released in urine but must be performed in a reference laboratory only.…”

Section: Discussionmentioning

confidence: 99%

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ImmunoCyt/uCyt+™ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma

et al. 2005

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ImmunoCyt/uCytt is a fluorescent test combining three monoclonal antibodies. In this study, it has been tested as a complement to cytology in the detection of urothelial carcinoma in urine. It has been performed simultaneously with standard cytology and cystoscopy on 870 urine analyses from one hospital. In 136 cases, one or more bladder tumors were found. Overall sensitivity of cytology, ImmunoCyt/uCytt and combined analyses reached 29, 74 and 84%, respectively, and overall specificity was 98, 62 and 61%. The negative predictive value of cytology, ImmunoCyt/uCytt and both analyses was 88, 93 and 95%, respectively, and the positive predictive value was 70, 26 and 29%. The sensitivity of cytology for low malignant potential neoplasms, low-and high-grade papillary carcinomas was 6, 18 and 53%, while it reached 71, 79 and 93% when combined with ImmunoCyt/uCytt. The sensitivity of cytology for stages Ta, T1, T2 and over and Tis tumors was12, 67, 47 and 50%, while it reached 78, 83, 79 and 100% when combined with ImmunoCyt/uCytt. In the absence of tumor on cystoscopy but with positive ImmunoCyt/uCytt, 18% of patients developed a tumor, 2-6 months later. Of the 109 cases diagnosed as suspicious for malignancy by cytology, a tumor was present in 30 cases and ImmunoCyt/uCytt was positive in 22 (73%) of them. In conclusion, ImmunoCyt/uCytt may be used to postpone cystoscopies in patients followed for bladder cancer and may help to save cytologist and pathologist screening Keywords: urothelial carcinoma; cytology; ImmunoCyt/uCytt; immunofluorescence; urinary bladder; recurrence Superficial bladder cancers are defined as tumors limited to the mucosa (Tis, Ta) or invading into the lamina propria (T1), without muscle invasion. 1 They represent more than 80% of urothelial carcinomas and more than 50% will recur. 1-3 Patients with bladder cancer are followed with regular cytologies and cystoscopies. Cytology is very specific but this test is limited by its low sensitivity ranging from 16 to 60%. 4 Cytology is most useful at detecting highgrade (HG) cancer, whereas its sensitivity for lowgrade (LG) urothelial tumors is low and merely reaches 17%. 4 Furthermore, criteria used in urinary cytology to detect tumor cells are largely subjective and the ability to detect cancer cells is dependent on the experience of cytologists or pathologists. For instance, atypical cells and papillary aggregates may be found in either reactive or neoplastic conditions. 5 Furthermore, LG urothelial carcinomas do not always exfoliate in aggregates and the cell characteristics are often so subtle that they might not be recognizable even by an experienced cytologist. 5 Standard practice in the follow-up of patients with bladder cancer requires cystoscopies at regular intervals, but this technique is invasive, costly and causes discomfort to the patient. It is thus estimated that by improving the sensitivity of cytology, fewer follow-up cystoscopies would be needed. Furthermore, improved sensitivity would help cytologists and pathologists to save time c...

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Section: Discussionmentioning

confidence: 99%

“…1 They represent more than 80% of urothelial carcinomas and more than 50% will recur. [1][2][3] Patients with bladder cancer are followed with regular cytologies and cystoscopies. Cytology is very specific but this test is limited by its low sensitivity ranging from 16 to 60%.…”

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ImmunoCyt/uCyt+™ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma

et al. 2005

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“…1 Many efforts have been made in search of biomarkers associated with histopathological features and biological behavior of urothelial carcinomas, 2,3 in order to achieve accurate grading, staging, and optimal management. Molecules involved in cell death and proliferation are among those receiving more attention, but their roles in urothelial carcinogenesis and tumor progression are not well understood.…”

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confidence: 99%

Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder

Chen

Zhang

et al. 2006

Modern Pathology

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The caspase family proteases are key proapoptotic proteins while the inhibitor of apoptosis proteins (IAP) prevent apoptosis by antagonizing the caspases or other key proapoptotic proteins. Limited studies of IAPs suggested their deregulation contributed to urothelial neoplasia. However, the expression status and biologic or prognostic significance of the caspase and IAP family proteins in urothelial neoplasms is not clear. In the present study, we first systematically evaluated the expression profile of the major apoptosis regulators, including caspases (CASP3,6,7,8,9,10,and 14), IAPs (survivin/BIRC5, CIAP1, CIAP2, XIAP, and LIVIN), APAF1, SMAC, and BCL2, as well as proliferation markers Ki67 and PHH3, in Ta/T1 human urinary bladder urothelial carcinomas and normal urothelium samples by immunohistochemistry. The analysis showed that survivin/ BIRC5 nuclear labeling index (BIRC5-N), but not cytoplasmic staining, was the only apoptotic marker which correlated significantly with tumor grade, stage, and patient outcome. We further analyzed the prognostic value of BIRC5-N in 101 Ta/T1 urinary bladder urothelial carcinomas by univariate analysis, which showed that BIRC5-N as well as the more classical prognosticators (stage, grade, and Ki67 index) were of prognostic significance. However, multivariate analysis by Cox proportional hazard regression demonstrated BIRC5-N was a stronger prognosticator than tumor grade, stage, and Ki67 labeling index. BIRC5-N index of 8% or more predicted unfavorable disease-specific survival (relative risk (RR) ¼ 6.6, 95% confidence interval ¼ 1.6-26.7, P ¼ 0.0080) as well as progression-free survival (RR ¼ 4.4, 95% confidence interval ¼ 1.3-14.6, P ¼ 0.0151). We conclude that BIRC5-N is a superior biologic and prognostic marker for Ta/T1 urothelial carcinomas of urinary bladder.

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“…1 T1 and T2a classification tumors often create a therapeutic dilemma that ideally would require a definitive prognosis factor, which so far remains undiscovered.…”

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confidence: 99%

Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma

Alonso

Pita-Fernández

González-Carreró

et al. 2002

Cancer

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BACKGROUNDDetermination of prognosis factors associated with survival, recurrence, progression, and development of metastasis in T1 and T2a transitional cell carcinoma (TCC) of the bladder is discussed.METHODSA study was conducted of a group of 210 patients with primary bladder TCC at classification T1 (n = 175) and T2aN0M0 (n = 35). A total of 177 variables were studied in each patient. The monoclonal antibodies used were the following: DO7 (p53) and MIB‐1 (Ki‐67). Prognosis was obtained using Kaplan–Meier methodology and Cox proportional hazards model.RESULTSThe average follow‐up period was 6.7 years. Cancer‐related survival rates at 5 and 10 years were 82.96% and 74.78%, respectively. The independent survival variables were the following: age and expression of p53. Recurrence free survival at 5 and 10 years stood at 51.80% and 42.71%, respectively. The independent recurrence variables were T2a classification, tumor multifocality, tumor size of greater than 3 cm, carcinoma in situ in random biopsy, and expression of Ki‐67. Progression free survival rates at 5 and 10 years were 75.31% and 69.16%, respectively. The independent progression variables were age, T2a classification, and expression of p53. Metastasis free survival rates at 5 and 10 years stood at 87.23% and 84.55%, respectively. The expression of p53 was the sole variable to provide an independent prediction of metastasis.CONCLUSIONSThe expression of p53 clearly has an independent effect on the prediction of survival, progression and development of metastasis, showing a dose–response effect. Tumor multifocality and T2a classification are the variables that best predict recurrence. Cancer 2002;94:1677–84. © 2002 American Cancer Society.DOI 10.1002/cncr.10376

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Prognostic Markers in Bladder Cancer: A Contemporary Review of the Literature

Cited by 237 publications

References 148 publications

ImmunoCyt/uCyt+™ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma

ImmunoCyt/uCyt+™ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma

Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder

Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma

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