Marieke van Son

11 GENERAL INTRODUCTION AND THESIS OUTLINE decisions, patients in the intermediate-risk group are frequently subdivided into favor- able (ISUP grade 2) and unfavorable (ISUP grade 3) risk groups(27). Table 1 – Risk stratification groups for patients with localized prostate cancer Low-risk (all) PSA <10 and ISUP 1 and cT1-T2a Intermediate-risk D’Amico/EAU/NICE – PSA 10-20 and/or ISUP 2-3 and/or cT2b NCCN – PSA 10-20 and/or ISUP 2-3 and/or cT2b-c High-risk D’Amico/NICE – PSA >20 and/or ISUP 4-5 and/or cT2c-T3 EAU – PSA >20 and/or ISUP 4-5 and/or cT2c or any PSA/ISUP with cT3-4 or cN+ NCCN – PSA >20 and/or ISUP 4-5 and/or cT3 or ≥2 intermediate risk features PSA: prostate specific antigen, ISUP: grade group by the International Society of Urological Pathology, EAU: European Association of Urology, NICE: National Institute for health and Care Excellence (UK), NCCN: National Comprehensive Cancer Network (US). Beyond local staging, further nodal and metastatic screening is strongly advised for unfavorable intermediate- and high-risk patients(24, 28). Although relatively modern imaging modalities (prostate specific membrane antigen [PSMA]-PET/CT and diffu- sion-weighted MRI) provide the most sensitive detection of lymph node and bone me- tastases(29-32), there remains hesitation regarding treatment of modern imaging-only detectable lesions since its clinical benefit in terms of overall survival has not yet been established(33). Although current guidelines still advise using a classical work- up with bone scan and abdominopelvic CT, recent level 1 evidence supports offering PSMA-PET/CT to high-risk patients(34). Treatments in the primary setting For patients with clinically localized non-metastatic prostate cancer, there are local treatment options with curative intent. Among these, surgery and radiotherapy are the two major contemporary approaches, with apparent equivalence in terms of overall survival. As long-term data from a randomized study (among predominantly low-risk patients) have shown, 10-year prostate cancer-specific mortality is very low (±1%)(35), which shifts the attention towards treatment-related side-effects. Radical prostatectomy (RP) entails the complete removal of the prostate and seminal vesicles, nowadays usually performed using a laparoscopic (LRP) or robot-assisted (RARP) approach(36). On average, intra- and peri-operative complications such as need for blood transfusion, organ injury, infection, or anastomotic leak are rare (<5%)(37), although patients with existing comorbidities are at higher risk of surgical complica- tions(38). Post-operative morbidity is a more common problem, mainly presenting in the form of urinary incontinence (±20% one year post-treatment) and erectile dysfunc- tion (ED) (±70-75% one year post-treatment)(39). Both are the direct result of surgically compromised critical structures, such as the external urethral sphincter and neuro- vascular bundles. Studies assessing the effect of sphincter reconstruction or bladder 1