Marieke van Son

181 GENERAL DISCUSSION AND FUTURE PERSPECTIVES received local staging in these studies. In contrast with prostate cancer in the primary setting, localized radiorecurrent disease is usually unifocal, occurring predominantly at the site of primary disease(33). It is likely that the primary dose to the dominant lesion within the prostate was often too low while microscopic disease elsewhere in the pros- tate was eradicated. This supports the use of targeted treatment in the salvage setting. Figure 2 – Anatomical patterns of prostate cancer relapse after primary radiotherapy. Image adapted from: Cancer Research UK, 2020 Beyond detection of prostate cancer presence, radiological findings alone cannot deter- mine the clinical significance of recurrent disease. It has been suggested that prostate biopsies are critical to confirm that the source of PSA progression originates from local disease recurrence(34). However, its interpretation is problematic with high occurrence of false negatives due to sampling error, false positives due to delayed tumor regression, and indeterminate biopsies showing radiation effect in residual tumor(35). Since the pathologic assessment of radiorecurrent disease falls short in accurately distinguish- ing clinically significant cancer, biopsy results are of limited value in predicting which patients will have long-term benefit from local salvage treatment and whom should be left untreated to avoid unnecessary side-effects. Understanding the true impact of biochemical recurrence after primary treatment is crucial, since it does not necessarily indicate that a patient will develop clinically relevant (metastatic) disease or will even die from the disease. Studies have shown that only certain patient subgroups, namely those with increased age, high initial ISUP grade, high PSA or short PSA doubling time, are at high risk of progressive disease(36, 37). In a recent systematic review on the natural history of recurrences after primary curative treatment, biochemical relapse after radiotherapy was associated with worse survival rates, but this was limited to men with a short interval to biochemical failure or men with a high initial ISUP grade(38). Within this review, the authors proposed recurrence stratification criteria, stratifying post-radiotherapy patients with an inter- 10