Timo Soeterik

162 CHAPTER 9 Prostate cancer is a common disease, which can present in a wide variety of stages. Accurate staging of prostate cancer is crucial for determining the most suitable treatment strategy, resulting in the best possible outcomes. Optimising primary tumour staging and consequent treatment indication for either invasive or non-invasive therapeutic strategies are therefore crucial to ensure patients are offered the best treatment. In this thesis, we explored a number of scientific topics within the context of prostate cancer, including: the evaluation of real-world active surveillance (AS) outcomes, focusing on patient selection criteria and follow-up intensity, the impact and value of magnetic resonance imaging (MRI) on staging as well as consequences of staging such as extent of surgery and implementation of MRI information into existing and novel prediction tools. In the following chapter, the findings of the performed studies presented in this thesis are summarized. PART I. OPTIMISING ACTIVE SURVEILLANCE In Chapter 2 , we conclude that patient selection for AS in the real-world clinical setting substantially differs from the selection of patients in a trial setting. Our analysis revealed that 49% of the patients in a real-world Dutch AS cohort did not meet one or more of the inclusion criteria used in the largest ongoing AS study (Prostate Cancer Research International Active Surveillance Study [PRIAS]). We observed large differences in AS outcomes comparing PRIAS-eligible and PRIAS-ineligible patients. PRIAS-ineligible patients experienced tumour progression during AS significantly earlier and had a three-fold increased risk of unfavourable surgical pathology after deferred radical prostatectomy, compared with PRIAS-eligible patients. Of all PRIAS selection criteria, PSA density (PSAD) was found to be a significant predictor for developing metastasized prostate cancer. Patients with PSAD ≥0.2 ng/ml/ml at diagnosis had a three-fold higher risk of metastasis, compared with patients with PSAD <0.2 ng/ml/ml. The novel insights regarding AS outcomes of patients who are selected “off-protocol”, can help guide patients and their treating physicians to determine if AS is a suitable treatment option, taking into account the patient’s baseline characteristics and preferences. In Chapter 3 , we report that AS follow-up in daily practice is also less stringent than advised by the prevailing AS follow-up protocols. Overall, less than half of all patients (43%) evaluated underwent PSA testing and repeat biopsies concordant with the PRIAS protocol. In patients meeting all PRIAS criteria at baseline (PRIAS-eligible), less frequent PSA monitoring as well as less frequent repeat biopsy were not associated with an increased risk of metastasis. Whereas among patients who were PRIAS-ineligible, concordant monitoring (especially PSA testing) is strongly advised, as discordant follow- up was associated with an increased risk of developing metastasized prostate cancer. Our findings suggest that it may be possible to loosen follow-up intensity in selected patients