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Exploring the aggressiveness of prostate cancer to enable an individualised treatment approach

Final Report Summary - EXACTA (Exploring the aggressiveness of prostate cancer to enable an individualised treatment approach)

Prostate cancer is one of the most frequently diagnosed malignancy in the western male population and the associated socio-economic impact on healthcare is more than worrying. The ERC Starting Grant project Exploring the aggressiveness of prostate cancer to enable an individualised treatment approach, has addressed the current key feature of confined (stage T2) prostate cancer: its true aggressiveness. Not all cancers are life threatening and early diagnosis, although needed to improve outcome, currently leads to overtreatment of patients with indolent prostate cancer resulting in unnecessary treatment-related morbidity. In this project, state-of-the-art MRI methods have been validated for their potential to discriminate between low and intermediate and high aggressive prostate cancer, leading to a large number of publications in scientific literature, not only in the field of Radiology, but also in Urology. The findings in this project, disseminated to experts in the field, contributed to the development of new standards in the prostate imaging and reporting system (PIRADS 2). In due time, the validated MRI methods will have an essential role in the active surveillance of patients with small-volume low-aggressive prostate cancer.
Next to near-clinical research, great progress has been made in developing new MRI methods for prostate cancer research at a ultra-high magnetic field strength of 7T. Anatomical imaging methods have been developed, and new spectroscopic imaging methods of cancer-related metabolites have been implemented (in so-called phosphorus spectroscopic imaging). New magnetic resonance hardware (radiofrequency coils) was developed, tested and approved for safe human use, and the initial measurements on patients with prostate cancer were successful: new possible biomarkers for prostate cancer aggressiveness have been discovered with phosphorus MRSI, and MRI at an unprecedented spatial resolution revealed more anatomical detail in in vivo MR examinations.
As a third pillar in this project, a dynamic nuclear polarisation system has been built for studies of prostate cancer cell systems. Apart from the polarization system itself, we developed a setup enabling dynamic measurements of metabolism on cell cultures of as little as 500.000 cells. Because of the small sample volumes, intra- and extracellular metabolite pools could be distinguished, which allows to calculate metabolite transport across the cell membrane. These studies are essential to interpret future in vivo work of hyperpolarized substrate in patients with prostate cancer, to better understand the disease, its stage and metastatic potential.