Marieke van Son

9 GENERAL INTRODUCTION AND THESIS OUTLINE Figure 2 – Trends in age-standardized cancer mortality rates among males in the United States. Image adapted from: Siegel et al., 2020(2) Prostate cancer is most frequently diagnosed among men aged 65-74, and it is more common in men of African ancestry, men with a genetic predisposition (e.g., Lynch syndrome and BRCA1 and BRCA2 mutations) or a family history of close relatives diag- nosed with prostate cancer, especially before the age of 65(8). At presentation, ±80% of patients have localized disease, ±15% has regional lymph node involvement and ±5% has distant metastases(9). Stage at diagnosis has a dramatic impact on 5-year relative sur- vival rates, with excellent survival for patients with localized or regional disease (>99%) and much lower survival for patients presenting with metastases (31%)(8). This not only reflects the aggressive nature of late-stage disease, but also the indolent nature of early-stage disease and potentially the effectiveness of local treatments for these tumors. Diagnosis and staging To improve accurate staging (and to provide a better framework for suitable choice of treatment), there has been a heavy focus on improving diagnostic imaging over the last years. Although several developments have led to improved cancer detection and potentially better patient selection, the challenge remains how to incorporate these new techniques in diagnostic pathways and, consequently, in treatment decisions. Although local tumor staging (Figure 3) is historically performed using digital rectal examination (DRE) and current guidelines still refer to DRE-findings for determination of the clinical T-stage(10), the role of multiparametric magnetic resonance imaging (mp-MRI) seems to become more prominent. Its added value in terms of initial cancer screening in biopsy-naïve patients has been under debate, considering its low specific- ity and therefore high number of false positives(11). Nevertheless it has been suggested that the combination of mp-MRI with clinical and biochemical data in a multivariate prediction model may aid in the decision process of whether or not to biopsy at all, thereby reducing the number of unnecessary biopsies(12). More established is its role as pre-biopsy visual aid, since mp-MRI allows for targeted biopsies which seem to im- 1