Timo Soeterik

11 General Introduction and Thesis Outline Clinical T-stage The cT describes the primary tumour’s size and extent. In prostate cancer, the conventional modality to establish cT of the tumour is by digital rectal examination (DRE). Findings established by DRE, such as palpation of a nodule or extraprostatic extension, were considered valuable to establish disease stage. 3 Ever since the first prostate cancer staging system was established, information regarding primary tumour size, assessed by digital rectal examination, was included as an essential component. 3 Throughout the years, staging systems have evolved and the cT is now part of the widely accepted tumour, nodal and metastasis (TNM) classification of malignant tumours. 4 At present, the 8 th Edition of the AJCC is used to define the cT (Table 1). 5 Histological grading of prostate cancer The first structured approach to grade prostate cancer based on the underlying histological architecture was developed in 1966 by Donald Gleason, who proposed a morphologic classification of prostate cancer. 6 The grading system showed to contribute significantly to the mortality rate prediction information, in addition to that provided by the clinical staging of the tumour. 7 To establish the Gleason score, the pathologist assigns a primary score and a secondary score. The primary score includes the most dominant pattern of the tumour, that has to be greater than 50% of the total pattern observed. The secondary score is based on the next-most frequent pattern, less than 50% of the total pattern, and at least 5%. Subsequently, the total score is summed resulting in the Gleason sum score, with a range of 2 to 10. Contemporarily referred to as the Gleason grading system, this scoring system has gained worldwide recognition allowing a more individualized approach to patients with prostate cancer. In 2005, the International Society of Urologic Pathology (ISUP) made the first revisions to the grading system. Modifications are based on novel insights regarding the prognostic implications of different histological patterns that can be found in prostate cancer specimens. Most recent updates were established during the ISUP consensus conference in 2014, wherein various grade patterns were defined and a new grading system of prostate cancer was proposed (Table 2). 8 1