MRI-targeted fusion-guided prostate cancer diagnostics - strategies to avoid overdiagnosis and overtreatment

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Prostate cancer (PC) is a leading cause of cancer-related morbidity and mortality in men. PC diagnosis is dependent on prostate biopsy. However, standard transrectal ultrasound-guided random biopsies may miss clinically important tumors and they also result in cancer detection in men who are unlikely to benefit from the diagnosis. Due to widespread adoption of PSA-testing, there is an eightfold difference between incidence- and mortality-rates in developed countries. While high risk tumors are still often detected too late, at the same time overdiagnosis and overtreatment of large numbers of biologically insignificant low risk tumors represent important clinical and economical problems.The optimal management of localized PC is critically dependent on an accurate assessment of the individualized risk of tumor progression within the lifetime of the patient. Although active surveillance should nowadays be the treatment of choice for indolent disease, still up to 40% of men shift to active therapy early during their active surveillance due to reclassification towards higher risk disease. To safely increase widespread use of active surveillance, PC diagnostics need to be refined in order to correctly identify aggressive disease from the start.Evidence is accumulating that multiparametric magnetic resonance imaging (mp-MRI) can be used to improve the performance of prostate biopsy. In this context we have developed a novel prostate biopsy system, which fuses pre-interventional MRI-data with peri-interventional ultrasound for image-guided transperineal prostate biopsies. This platform enables accurate examination of all regions of the prostate and exact targeting of cancer-suspicious lesions. The first goal of this proposal is to validate the efficacy and accuracy of mp-MRI and MRI-targeted fusion-guided prostate biopsies to detect clinically significant cancers as compared to specimen obtained by radical prostatectomy as reference standard. Furthermore, we aim to prospectively optimize image-guided prostate biopsy protocols and numbers of cores needed to reduce overdiagnosis of indolent tumors without underdetecting aggressive disease.Using novel 3D-image-guided tissue sampling we want to achieve unprecedented diagnostic accuracy. The results of this proposal will increase patient safety and further individualise the management of PC patients. Ultimately, they will be valuable to prevent overdetection and overtreatment of men with indolent disease.