The Bladder Cancer Group at MOMA

About Bladder Cancer

Bladder cancer is the fifth most common neoplasm in industrialised countries. Risk factors include tobacco smoking and occupational exposure to carcinogens. The prevalence is three to eight times higher than the incidence, making bladder cancer one of the most prevalent neoplasms, and hence, a major burden for all health care systems. 

Non-muscle invasive tumors (Ta and T1)

The most frequent form of all newly diagnosed cancers is the stage Ta tumor. The prognosis of these tumors is good as more than 90% never progress to higher stages with conservative treatment.
However, more than 70% of the tumors recur in the bladder, which makes this tumor type responsible for the high prevalence rate. Consequently, after transurethral resection of the tumors, an attempt to prevent recurrences is frequently made by intravesical instillations of Bacille Calmette-Guerin (BCG). The surgical removal of the whole bladder (cystectomy) may be considered in selected cases of patients with very frequent recurrences, high grade lesions and failure of BCG treatment.

Invasion of the lamina propria (stage T1) is evident at diagnosis in about 20% of all cases. These tumors have a worse prognosis and most will be fatal if not treated aggressively.

CIS

Carcinoma in situ (CIS) is rarely diagnosed as the primary lesion; concomitant CIS is more common, and may be found in up to 40% of stage T1 cancers and in 50% of the muscle invasive stages. CIS is treated by BCG instillations. In case of failure, cystectomy is the treatment of choice. About 30% of stage T1 tumors of the CIS-type will progress to muscle invasion under a conservative regimen. Large tumors and tumors with multiple recurrences or widespread CIS have a very high risk of progression, so many of these cases are primarily offered radical treatment.

Muscle invasive tumors (T2 to T4)

Muscle invasive bladder cancer (stage T2-4) is a fatal disease if left untreated. Although endoscopic and partial bladder resections may cure the disease in selected cases, the standard treatment today is the complete removal of the bladder (radical cystectomy).
Unfortunately, a substantial fraction of muscle invasive bladder cancers have distant metastases already at this stage, and this is critical for the long term prognosis. Metastatic disease is treated by chemotherapy. Five year cause specific survival rates are stage dependent and rank from 40% (stage T2) to less than 10% (stage T4).

Molecular Markers

There is an urgent need for highly sensitive and specific molecular markers that:

identify bladder tumor recurrences in plasma or urine

predict subsequent disease progression in early stage bladder cancer

identify metastatic disease prior to cystectomy

predict if the patients respond to chemotherapy.

Aim of Research

We aim at performing translational research to identify and validate molecular markers that pave the way for optimal personalized treatment regimens. Furthermore, we want to obtain a better understanding of the molecular biology of the disease and the underlying affected molecular pathways.

Bladder Cancer Tissue Bank

Most of our research is based on our large bladder cancer tissue bank (MOB). It currently contains more than 70,000 samples of tumor tissue, blood and urine from more than 2600 patients with bladder cancer, prospectively collected since 1994 in close collaboration with the Department of Urology, Pathology and Oncology at Aarhus University Hospital. All information is organized in a database, including detailed pathology information, treatment regimens followed, and sample characteristics (size, growth pattern, multiplicity, concomitant carcinoma in situ).

We have constructed several tissue microarrays (TMAs) based on formalin fixed paraffin embedded (FFPE) tumors for validating key molecular markers in large patient cohorts. A progression TMA (284 tumors) and a metastasis TMA (400 tumor) are currently available. The tissue bank has been approved by the Central Denmark Region Committee on Biomedical Research Ethics and the Danish Data Protection Agency.

 

Current research activities

• EU FP7 project: Prospective multicenter evaluation of gene expression signatures for disease outcome and establishment of risk scores for outcome predicting combining molecular markers and clinical risk factors. See www.uromol.eu.

• Long non-coding RNAs as biomarkers and novel drivers of human bladder cancer

• Deep sequencing of bladder tumors to discover novel molecular pathways involved in disease progression.
• Exosome characterization and function in bladder cancer.
• Identification of diagnostic and prognostic genomic tumor alterations to be used individualized patients follow-up and surveillance screening using plasma and urine samples.
• Identification and validation of molecular markers for predicting disease outcome and treatment response in advanced bladder cancer.