Download Objectives Prostate cancer (PCa) is the most common malignancy in

Objectives
Prostate cancer (PCa) is the most common malignancy in Western men. When localised within the
prostate, the tumour can be treated by radiotherapy or surgical removal of the prostate. However, a
substantial number of patients suffer relapse due to metastatic tumours that can only be treated by
palliative therapy.
The Prostate Cancer Molecular Medicine (PCMM) project will address two major clinical needs. Firstly,
the need to reduce overdiagnosis and overtreatment of prostate cancer due to today’s less than ideal
screening tests (PSA tests). Secondly, the need for better therapy monitoring techniques for advanced
disease.
To improve overdiagnosis, the project will attempt to develop and validate novel biomarkers in blood,
urine and tissue that can be used to differentially diagnose and evaluate prognosis for individual patients,
and that can also be applied for tailored treatment. To improve therapy monitoring for metastatic tumours,
it will develop and test innovative imaging tools that can be used to visualise and evaluate early response
to treatment, allowing therapy management at the level of the individual patient.
The biomarker and imaging studies in PCMM will be facilitated by a unique Dutch prospective biobank
composed of biological specimens and imaging data from patients with various stages of prostate cancer.
An IT infrastructure will be designed that allows for the integration of clinical and research data in a
central database.
Prostate Cancer Molecular Medicine (PCMM) – Erasmus University Medical Centre, Rotterdam
Principal Investigator: Professor Chris H. Bangma
CTMM Program manager: Eric Caldenhoven
In The Netherlands, prostate cancer is the most frequent malignancy and one of the major causes of
cancer-related death in men. The diagnosis of prostate cancer is increasing as a result of the more
widespread use of a screening test that measures the level of Prostate Specific Antigen (PSA) in blood.
The disease can be treated by curative therapy, such as surgical removal of the prostate or radiotherapy,
if at the time of diagnosis the tumour is still localised within the prostate. However, a substantial number
of patients experience a relapse after curative therapy. In these patients, the tumour has typically
escaped the prostate and metastasised to other parts of the body, with a preference for the skeleton. This
advanced stage of prostate cancer can only be treated by palliative therapy, initially by hormonal
treatment aimed at temporarily slowing down tumour growth and in the final stages by chemotherapy to
reduce pain and improve quality of life.
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Reduction in over-diagnosis and over-treatment
The Prostate Cancer Molecular Medicine (PCMM) project will address two major clinical needs in prostate
cancer care. The first is the need for a reduction in over-diagnosis and over-treatment of the disease due
to PSA test screening. Prostate cancer is diagnosed via a biopsy that determines the presence of tumour
cells in the prostate, the biopsy being performed as a result of an elevated level of PSA in the blood.
Recently, the Rotterdam-based European Randomised Study of Screening for Prostate Cancer
demonstrated that the use of PSA as a screening tool in men aged 55-70 reduces the rate of death from
prostate cancer by at least 20%. However, it also demonstrated that the PSA test is associated with a
high risk of over-diagnosis. This is because PSA levels are not only increased by prostate cancer. They
can also be increased as a result of other conditions such as benign prostate enlargement. Unnecessary
biopsies are therefore being performed in a significant number of screened men.
In addition, PSA is a poor predictor of the aggressiveness of a prostate tumour. About 50% of the cancers
detected by screening are harmless and not life threatening, and can therefore best be treated by active
surveillance. Since PSA cannot adequately discriminate between these indolent tumours and tumours
that require invasive therapy, a large number of men diagnosed with prostate cancer are unnecessarily
treated by surgical removal of the prostate or radiotherapy. Unfortunately, these treatments are
associated with highly unpleasant side effects, such as impotence and incontinence. There is therefore a
strong need for biomarkers other than PSA to reduce worldwide over-diagnosis and over-treatment in
men who undergo screening for prostate cancer.
The PCMM project will develop and validate novel biomarkers in blood, urine and tissue that can improve
the diagnosis and prognosis of prostate cancer, and that can also be applied for tailored treatment of this
malignancy.
Improvement of therapy monitoring
The second clinical need addressed by the PCMM project concerns the improvement of therapy
monitoring for advanced prostate cancer. In clinical practice, the level of PSA in blood is also used as a
tool to monitor the response of a prostate tumour to treatment. However, especially in advanced prostate
cancer, PSA is a less suitable marker to assess the effect of treatment on metastases. As a result,
clinicians require a therapy-monitoring tool that can visualise metastatic lesions in bone and other parts of
the body. The PCMM project will develop and test accurate, innovative imaging tools that can be used to
visualise and evaluate early response during treatment, enabling health care management at the level of
the individual patient. These tools could also be used to address the urgent need for more effective
clinical assessment of new candidate drugs.
The biomarker and imaging studies in PCMM will be facilitated by a unique Dutch prospective biobank
composed of biological specimens and imaging data from patients with various stages of prostate cancer.
This will be established within the Dutch ‘String of Pearls’ biobanking initiative.
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Based on the data from this PCMM biobank, an infrastructure will be created that will facilitate the
integration of biomarkers and imaging outcome in a future clinical decision support system for prostate
cancer. It is expected that such a system will be introduced in clinics in the near future in order to assist
physicians in selecting the best individual treatment strategy for patients suffering from prostate cancer.
The PCMM consortium is composed of 11 partners, including the four top urological academic hospitals
in The Netherlands, the best Dutch prostate cancer biomarker and imaging research groups, and wellrecognised pharmaceutical, diagnostics and technology companies. By developing novel diagnostic,
prognostic and therapy monitoring tools for prostate cancer, the PCMM project will contribute to the
worldwide need to improve the quality of life for a growing number of men diagnosed with prostate cancer
and the need to develop tailored treatment for these patients.
Budget, organization and partners
Project budget 15 M€
Start date: 01-12-2009
End date: 30-11-2014
4 Industrial partners
6 Academic partners
ASTELLAS Pharma Europe BV
Dionex Benelux BV
NovioGendix Research BV
Philips Electronics Netherlands BV
Erasmus University Medical Center
Netherlands Cancer Institute
Radboud University Nijmegen
University Medical Center Groningen
University Court of University Glasgow
University of Verona
Allocated at year-end-2011:
53 researchers (21.4 FTEs)
General
In response to the first call for project proposals in 2007, the Center for Translational Molecular Medicine (CTMM)
announced on April 1, 2008, that nine first-call projects would receive research funding amounting to a total of 150
million Euro. On March 10, 2009, it announced that eight new project proposals, submitted in the fall of 2008 in
response to the second call for proposals, will receive funding amounting to a total of almost another 100 million
Euro. On August 4, 2009, it announced further funding of 15 million Euro for the following research project on
prostate cancer.
All Dutch university medical centres, plus several universities, a broad spectrum of small and medium-sized
enterprises, major industry leaders including Philips and DSM, and the Dutch Government are involved in CTMM
projects. The funding is provided by the Dutch government, industry and academia. The research is focused firmly on
the ‘translational’ aspects of molecular medicine so that results can be applied as quickly as possible to actual patient
care. PCMM is one of the projects from the second call.
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