General introduction and thesis outline 15 NCCN risk group Clinical/pathological features Very low-risk T1c AND grade group 1 AND PSA < 10.0 ng/mL AND < 3 positive biopsy fragments/cores with £ 50% cancer in each AND PSA density < 0.15 ng/mL/g. Low-risk T1-T2a AND grade group 1 AND PSA < 10.0 ng/mL AND does not qualify for Very low-risk. Intermediate-risk Intermediate-risk factors: - T2b-T2c - Grade group 2-3 - PSA 10.0-20.0 ng/mL Favourable No more than one intermediate-risk factor (see left) AND grade group 1-2 AND < 50% positive biopsy cores. Unfavourable Two or more intermediate-risk factors (see left) AND/OR grade group 3 AND/OR ³ 50% positive biopsy cores. High-risk T3a OR grade group 4-5 OR PSA > 20.0 ng/mL AND does not qualify for Very high-risk. Very high-risk T3b-T4 OR primary Gleason pattern 5 OR > 1 High-risk feature OR > 4 cores with grade group 4-5. active surveillance.40 In patients with high-risk disease on the other hand, aggressive multi-modal treatment should be provided and mostly consists of either radiotherapy with systemic androgen deprivation therapy (ADT) and/or a brachytherapy (see ‘Radiotherapy techniques’) tumour boost or surgery with additional radiotherapy to the prostate bed or ADT.28 Patients with localised intermediate-risk prostate cancer are usually treated with radiotherapy (with or without ADT and/or a (brachytherapy) boost) or RP (with or without pelvic lymph node dissection [PLND]).28 With RP, the entire prostate gland and seminal vesicles are surgically removed. This surgery is nowadays often performed using a laparoscopic, robot-assisted approach (robot-assisted radical prostatectomy [RARP]). This approach usually shows low complication rates (< 5%).41 Potential complications for RP include excessive blood loss needing blood transfusion, organ injury, infection, and anastomotic leakage.41 However, post-operative comorbidity is much more common and can have a major impact on quality of life.42 This mainly consists of urinary incontinence (up to 21% at one year post-surgery) and erectile dysfunction (up to 75% at one year post-surgery) and the incidences depend, apart from patient characteristics, on the surgical technique, the surgeon, and hospital volumes.28,42,43 In addition to surgery and radiotherapy, several investigational treatments for localised prostate cancer exist. These include freezing (cryotherapy) and heating (high-intensity focused ultrasound [HIFU]) of the tumour and prostate.28 For cryotherapy, cryo-needles are inserted into the prostate under ultrasound-guidance. HIFU, on the other hand, uses focused ultrasound as a therapeutic mean. Although outcomes in small, single arm case-studies have been published, directly comparative data with surgery and/or radiotherapy is scarce.44 Table 2 – National Comprehensive Cancer Network (NCCN) prostate cancer risk groups. 1
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