INVASIVE BLADDER CANCER - Aspects on staging and prognosis

Abstract: Background: The difficulty of determining the prognosis for the individual patient with invasive bladder cancer is a major clinical problem. Currently, decisions regarding therapy are mainly based on tumour stage and grade, the first of which is notoriously demanding to ascertain. New molecular markers are however proposed to be of prognostic value. At present, there is considerable debate regarding the effects of delay on prognosis, lymph node staging and detection and staging of transitional cell carcinoma (TCC) involving the prostatic urethra and prostate in males. This thesis is based on investigations of the impact of diagnostic and treatment delay on prognosis in invasive bladder cancer (Papers I and II). Intra-operative sentinel node (SN) detection for lymph node staging is evaluated prospectively in Paper III, as are the incidence of TCC in the prostatic urethra and prostate and the preoperative detection of such tumour growth in Paper IV. The prognostic values of expression profiling and tissue microarray (TMA) in high-risk bladder cancer are investigated in Papers V and VI. Results and conclusions: 1) Diagnostic delay in patients with T1 tumours might have an adverse effect on the prognosis. 2) Treatment delay in patients with invasive bladder cancer submitted to radical cystectomy did not influence disease-specific survival or stage progression in the present study. 3) Intraoperative SN detection is feasible during radical cystectomy and improves nodal staging. 4) Preoperative biopsies from the prostatic urethra identified 66% of patients with TCC in the prostatic urethra and/or prostate in a prospective study investigating the prostate and bladder neck with sagittal whole-mount technique. 5) Preoperative investigation with cold cup mapping biopsies has a low sensitivity for detection of CIS (23%) and is probably of little clinical value for identifying patients at risk of TCC in the prostatic urethra/prostate in the cystoprostatectomy specimen. 6) Expression profiling identified a 50 gene signature predicting lymph node metastasis and survival in patients submitted to radical cystectomy. 7) TMA-based analysis of prognostic markers in invasive bladder cancer seems to be of limited value.