Timo Soeterik

18 CHAPTER 1 compared with DRE, on existing and novel prediction models includes an important research area that deserves further exploration. ACTIVE SURVEILLANCE Contemporary state of knowledge on active surveillance In the mid-twentieth century, prostate cancer was mostly detected when it had reached an advanced and incurable stage. 3,41 Nowadays, the most common presentation includes screen-detected asymptomatic localised prostate cancer. 42 Although detection of the disease in an earlier stage by screening leads to an overall higher likelihood of curation, it also increases diagnosis of indolent cancers which may not have caused any harm. 43 To prevent unnecessary treatment-related morbidity in newly diagnosed patients, expectant management strategies can be initiated. Expectant management can grossly be divided into two strategies: watchful waiting (WW) or active surveillance (AS). WW refers to conservative management for patients deemed unsuitable for treatment with a curative intent because of limited life expectancy. Within this context, patients are “watched” for the development of local or systemic progression. Palliative treatment can eventually be initiated according to their symptoms. AS aims to avoid unnecessary treatment in men who have prostate cancer who do not need immediate treatment, but at the same time aims to achieve the correct timing for curative treatment in those who eventually do. 17 Since the introduction of AS, significant progression has been made in reducing unnecessary treatment in patients who harbor prostate cancer showing to follow an indolent course. Based on the current ongoing AS registries, using AS can lead up to 58% of patients that remain untreated at 15 years of follow-up. 44,45 Several prospective cohort studies have been initiated showing favourable results. 46 However, AS outcomes have been described for a specific selected subgroup of patients with very low-risk disease characteristics. Although there is some variation regarding eligibility criteria used in AS studies, the selection criteria generally include: clinical stage T1c, Gleason sum score ≤6 (Gleason grade group 1), PSA <10 ng/ml, maximum of two biopsy cores with cancer and ≤50% involvement in any core. 47 Strictly adhering to these selection criteria leads to, potentially unjustified, exclusion of a substantial number of low-risk patients from AS. For instance, patients are advised against AS if in more than two biopsy cores prostate cancer is found, even if this includes ISUP 1 grade disease; the least aggressive form of prostate cancer of which it is known to only rarely metastasize. 48 It is attainable that AS can also be a safe strategy in patients with higher- risk tumour characteristics, not fulfilling all very low-risk criteria. Given the potential benefit of AS in terms in quality of life outcomes, applicability of AS in patients that harbor higher-risk tumour characteristics should be explored. Unfortunately, due to the strict inclusion criteria used in the ongoing AS studies, the number of patients with higher risk characteristics on AS in a trial setting is limited. Only few studies have described