## 1 Introduction  
In 1853, [PERSON], a surgeon at the London Hospital, diagnosed a cirrhosis of the prostate gland as an orphan disease, the first described case of Prostate Cancer (PCa). In 2020, the disease was responsible for 7.3% of all cancer deaths in men and was the second most frequent malignancy [1]. The prostate gland is about the size of a walnut and located in the pelvis surrounding the prostatic urethra and below the bladder. Usually, PCa originates from the peripheral zone of the prostate, adjacent to the rectum [2]. Silently asymptomatic in an early stage, PCa is usually diagnosed by a Digital Rectal Examination (DRE) and a Prostate Specific Antigen (PSA) blood test. The aggressiveness of PCa is quantified by the Gleason Grading System [3]. Based on the glandular architecture of cells, the pathologist assigns a grade of 1 if prostate cells are uniformly packed, up to a grade of 5 depending on pattern irregularity. The most predominant pattern and the second most prevalent are identified and graded accordingly,and finally summed to obtain the Gleason Score (GS), proportional to PCa aggressiveness [4]. In 2014, [PERSON] et al. [5] proposed a new Gleason grading system when several studies showed that a GS 7 = 4 + 3 had a worst prognosis than GS 7 = 3 + 4. A deeper stratification by Grade Group (GG) was then possible, including the most likely prognosis. The low/very low Risk Group (RG) is assigned to patients with a GS \(\leq\) 6. The intermediate RG includes patients classified with a GS of 7, with both favourable (3+4) and unfavourable (4+3) prognosis. Finally, the high/very high RG includes patients with a GS \(>\) 7. GS plays an important role in the determination of the type of treatment to follow. A low-grade cancer with a GS 6, together with a low PSA level and a small tumor may be an indication for active surveillance only. PCa evaluation takes into account the PSA levels, GS, TNM, patient history and physical examinations in order to provide a decision baseline for proper treatment and success prediction. Current guidelines suggest External Beam Radiotherapy (EBRT) as a curative option for localised and locally advanced disease and as a palliative option for metastatic low-volume disease [6]. The effectiveness of the treatment usually relies on the monitoring of PSA blood levels, the current reference biological test. Although a high value is associated with an increased risk of PCa, it is not PCa specific. High values of PSA are also associated with Benign Prostatic Hyperplasia (BPH), an enlarged prostate gland [7]. With the wide availability of PSA tests and the known long-term effects of definitive therapy, overdiagnosis and overtreatment have become a major issue. PCa treatments may cause sexual dysfunction, infertility, bowel and urinary problems [6], and so more conservative approaches such as active surveillance or watchful waiting have been adopted [8]. These are valid options, even for intermediate risk patients with a favourable prognosis (GS = 3 + 4). During the EBRT workflow, many imaging modalities are available. The Computed Tomography (CT) provides the Hounsfield Unit (HU) values critical for dose estimations. For PCa, Magnetic Resonance Imaging (MRI), providing superior soft-tissue resolution, is used for volume delineation. Positron Emission Tomography (PET) provides tumour cells' metabolic insights and finally, the Cone Beam Computed Tomography (CBCT), acquired during EBRT sessions, is used for patient positioning and setup verifications. Quantitative analysis of medical images may have a similar prognosis power to phenotypes and gene protein signatures [9]. This is the hypothesis behind radiomics (the extraction of features from radiographic images using data-characterization algorithms). As an emerging field in medicine, radiomics provides the quantification of phenotypic characteristics in medical imaging [10].