Diagnostic and predictive tools in localized prostate cancer : biopsies, magnetic-resonance imaging, and tissue markers

Prostate cancer (PC) is the most common non-cutaneous cancer in Western men. In Finland, 4500-5000 new cases are diagnosed annually. There is great variability in the clinical course of PC. Patients are therefore stratified into risk groups, reflecting how aggressive their PC is and how actively it should be treated and monitored. Currently, risk stratification is based on diagnostic prostate biopsies, the patient’s prostate-specific antigen level, and the disease’s clinical stage. This system has well-established limitations. The biggest uncertainty stems from prostate biopsies, which can be inaccurate. The current system also ignores prostate magnetic-resonance imaging (MRI), which is already widely used. Prognostic tissue markers from cancer samples could possibly improve the prediction of patients’ outcomes. This thesis study was carried out at the Department of Urology at Helsinki University Hospital during 2011-2016. The study looked into the safety (Study I) and diagnostic performance (Study II) of transrectal prostate biopsies, the value of prostate MRI in the follow-up of patients on active surveillance (AS) (Study III), and the correlation of tissue markers with clinical outcomes of patients following radical prostatectomy (RP) (Study IV). Study I: The incidence of severe infections following transrectal prostate biopsies has increased alarmingly in recent years. In Study I, we retrospectively evaluated the incidence of bacteremic post-biopsy infections in the Helsinki and Uusimaa hospital district during 2005-2013. A 2.4-fold increase was observed over the study period. In Study II, we retrospectively investigated in RP specimens of 96 men operated at our institution between 2009 and 2010 the performance of 12-core prostate biopsies in predicting tumor location and extent. We found biopsies to be inaccurate, which makes them a poor tool for detailed planning of radical or focal therapies. Study III was a prospective study investigating the value of prostate MRI in the follow-up of AS patients. In 2009-2011, 80 men at our institution underwent prostate MRI after being on AS for one year. We found prostate MRI to, at the time, add no value to the standard follow-up of AS patients. In Study IV, we retrospectively analyzed 815 men treated with RP between 1983 and 2005 at Helsinki University Hospital and at Turku University Hospital. The association of expressions of three PC tissue markers–ERG, PTEN, and AR–with clinical outcomes—requirement for secondary therapy after RP, disease-specific survival, and overall survival—were explored. Loss of PTEN expression appears to be a strong driver for disease progression, and its performance as a prognostic tool should be further studied in prospective settings.