Elsevier

European Urology

Volume 41, Issue 1, January 2002, Pages 15-29
European Urology

Molecular Aspects of Bladder Cancer: III. Prognostic Markers of Bladder Cancer

https://doi.org/10.1016/S0302-2838(01)00007-0Get rights and content

Abstract

The current pathological and clinical parameters provide important prognostic information, yet still have limited ability to predict the true malignant potential of most bladder tumors. In the last years, investigation of the basic mechanisms involved in carcinogenesis and tumor progression by molecular biology has provided a host of markers which are of potential diagnostic or prognostic value for bladder carcinoma. These markers may serve as tools for early and accurate prediction of tumor recurrence, progression and development of metastases and for prediction of response to therapy. The precise prediction of tumor biological behavior would facilitate treatment selection for patients who may benefit from radical surgical treatment or adjuvant therapy.

We provide a current, comprehensive review of the literature on bladder tumor markers with a special emphasis on their prognostic potential.

The literature suggests that currently no single marker is able to accurately predict the clinical course of bladder tumors and thus would serve as a reliable prognosticator. A combination of prognostic markers could predict which superficial tumors need an aggressive form of therapy and which invasive tumors require adjuvant therapy. Altogether, the most promising markers are, at this point, Ki-67 and p53 expression as well as matrixmetalloproteinase complex and angiogenesis.

Introduction

Molecular markers are potential tools for the detection of bladder cancer but also for the prediction of tumor recurrence and progression and for the development of metastases. We previously provided a review of markers with diagnostic value in the detection of bladder cancer [1]. In this article, we will focus on molecules that may serve as prognostic indicators.

Up to 80% of patients with superficial bladder carcinoma will have recurrent tumors after transurethral resection while, dependent on tumor stage and grade, approximately 25% of these patients develop progredient disease [2], [3]. The 10% of all patients with superficial bladder carcinoma progress to muscle-invasive tumors [4]. The majority of Ta tumors are low grade. Although these tumors frequently recur, less than 5% progress to invasion [5], [6]. In contrast, most T1 tumors are high-grade and 30–50% eventually progress in stage [7], [8]. High-grade Ta tumors have a 10–15% higher risk of progression than low grade Ta tumors but less than that of T1 tumors [9]. Unfortunately, in those patients with muscle-invasive bladder cancer, approximately half will develop metastatic disease. Intravesical Bacillus Calmette-Guerin (BCG) prophylaxis has lowered the cumulative disease progression rates of superficial tumors [10]. However, early failure is associated with poor prognosis, and this has prompted some authors to advocate primary cystectomy for high risk superficial tumors [11]. This strategy is associated with a high 5-year survival rate, but some patients may be overtreated [12].

As it is crucial to establish the intrinsic biologic behavior of the presenting lesion (in cases of both superficial and invasive tumors) and to determine whether the patient may be at risk for recurrence, or recurrence with progression, it would be useful to distinguish responsive from nonresponsive tumors as well as metastatic from locally invasive cancers [13]. Various pathological and clinical parameters, such as tumor grade, stage, multiplicity or size have been associated with adverse prognosis. Although these parameters provide a certain degree of tumor biological potential, a significant degree of tumor heterogeneity remains even within prognostic subgroups. With increasing understanding of the cellular mechanisms underlying the development of cancer several groups of potential molecular markers have been identified in the past years. These markers may serve as tools for early and accurate prediction of tumor recurrence, progression and development of metastases. The ability to predict precisely true tumor biological potential would enable the urologist to decide which superficial tumors require aggressive treatment and which invasive tumors would require adjuvant therapy additional to cystectomy.

Section snippets

Methodology

In the present article we provide a comprehensive review of prognostic bladder tumor markers (Table 1). To obtain literature on each of the markers we performed an online PubMed search. Terms for the PubMed search included bladder cancer, bladder tumor markers, review, tumor markers, molecular markers, immunohistochemistry, prognostic indicators, prognosis and the names of the individual bladder cancer markers. The search was not limited to any particular period. We referenced and discussed as

Tumor associated antigens

Antibody screening studies produced a number of monoclonal antibodies that are more or less specific to transitional cell carcinoma of the bladder. Some of the antibodies or the corresponding antigens have clinical value as diagnostic markers [1]. However, only the T138-antigen achieved not only diagnostic but also prognostic relevance. The T138-antigen is a glycoprotein cell surface antigen which is expressed in 15% of superficial and 60% of invasive tumors. 80% of patients with T138-positive

Conclusion

In this review we have presented the current knowledge about the value of potential prognostic markers in monitoring bladder cancer. It is common for most of the markers to be disregulated and inappropriatly expressed, in amount and in location, in bladder cancer. The ideal tumor marker should be objective and interpreter independent and results should provide prognostic information complemetary to that obtained on histopathological evaluation or imaging studies. Furthermore, it should predict

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