Timo Soeterik

168 CHAPTER 10 In this thesis, we have evaluated patient selection and follow-up for active surveillance in a real-world patient cohort, and related selection and follow-up intensity to oncological outcomes. Additionally, we evaluated the impact of incorporating prostate MRI information into risk classification systems and nomograms to assist primary staging of prostate cancer, and treatment consequences of MRI including extent of surgery. This chapter is a discussion of the main findings and their implications, and future perspectives. EVALUATION OF ACTIVE SURVEILLANCE IN REAL-WORLD CLINICAL PRACTICE Our analysis revealed that in real-world practice, 49% of patients on AS for prostate cancer are selected “off-protocol”; not fulfilling the traditional eligibility criteria used in the landmark AS studies such as the Prostate Cancer International Active Surveillance Study (PRIAS) (Chapter 2). 1 Although number of studies performed describing the outcomes of “off-protocol” (PRIAS-ineligible) selected patients are scarce, our findings implicate that AS is frequently advised in these patients, even though outcomes of AS in these patients are relatively unknown. In order to fill this scientific gap, we established rates of metastasis, risk of biochemical recurrence and outcomes of deferred surgery for both PRIAS-eligible and PRIAS-ineligible patients. These results show that PRIAS-ineligible patients experienced tumour progression significantly earlier than PRIAS-eligible patients, and had a three-fold increased risk of unfavourable surgical pathology after deferred radical prostatectomy. Our study also resulted in the identification of PSA density (PSAD) as an important prognostic parameter for unfavourable outcomes. For instance, PSAD ≥0.2 ng/ml/ml at diagnosis was associated with a three-fold higher risk of metastasis, compared with patients with a PSAD <0.2 ng/ml/ml. Identification of such clinically relevant predictors of AS outcomes is important, since these parameters and their related outcomes enable more individualized treatment decision-making. A limitation of the study is that the vast majority of patients (97%) were diagnosed by transrectal ultrasonography guided systematic biopsy, without prebiopsy MRI and target biopsy. 1 As systematic biopsy is associated with missing one-third of clinically significant tumours on initial biopsy, this may limit the generalisability of the results to the contemporary population of patients on AS in whom pre-biopsy MRI and subsequent target biopsy are increasingly used. 2 Another important limitation of this study includes the lack of comparative analysis of PRIAS-ineligible patients on AS with a matched patient cohort undergoing immediate radical treatment. Consequently, we were not able to conclude if better overall oncological outcomes would be achieved if this subset would undergo immediate active treatment. Future studies should focus on revealing the most optimal treatment strategy for PRIAS-ineligible, low to favourable intermediate-risk