This proposal focuses on diagnostic issues directly related to the selection and outcome of appropriate treatment regimens aimed at increasing the survival rates of prostate cancer (PC) patients. We intend to :
1. Construct highly sensitive and specific techniques to improve the early, cost effective detection of aggressive, organ confined and curable PC.
2. Construct sensitive and specific techniques that at an early phase can detect micrometastatic dissemination of the tumour in the blood circulation.
3. Identify molecular markers in tissue and blood to distinguish aggressive life-threatening cancers from non-aggressive, latent tumour lesions.
The proposed research goals are distinct, though relevant to those of the European Randomised study of Screening for Prostate Cancer (ERSPC) supported by EC grants.
The interactive programme involves 5 established European research groups (four academic and one from the industry) with long-term records of successfully combining fundamental, applied and clinical research. Two groups are from the Netherlands (Rotterdam, Nijmegen), one group from Sweden (Malmö) and two groups from Finland (Turku). The three clinical centres co-operate in prospective collection and analyses of tissue and blood specimens from patients and controls. A retrospective material with follow-up data is obtained from the ERSPC pilot study in Rotterdam : ~400 PC patients and ~1700 control subjects. The number of prospectively diagnosed cases of PC from the three clinical study sites will be ~600 patients per year.
The research goals are :
1. To design sensitive, specific and standardised methods for the early detection of PC by(i) constructing assays for multiple forms of PSA and glandular kallikrein (hK2) in serum, (ii) analysing collected sera at three clinical sites, (iii) comparing the obtained data with those of presently available test (total PSA, digital rectal examination (DRE) and transrectal ultrasonography) in order to evaluate their clinical utility and to reduce the number of unnecessary biopsies.
2. To design sensitive, specific and standardised techniques to distinguish aggressive from non-aggressive and possibly also organ confined from metastatic PC by (I) detecting specific mRNAs for PSA, hK2, prostate specific membrane antigen and the androgen receptor from micrometastatic cells in the blood, (ii) evaluating these techniques clinically.
3. To study tissue parameters that may distinguish aggressive from non-aggressive PC by : (I) developing standardised procedures for morphometric analysis and cytochemical detection of tissue markers, and by (ii) evaluating the data from the developed procedures with clinical data.
Funding SchemeCSC - Cost-sharing contracts
6500 HB Nijmegen
205 02 Malmö