Marieke van Son

64 CHAPTER 4 it possible to further escalate the dose to the tumor, without compromising the dose constraints for the organs at risk [13]. This feature can also be used to deliver a con- current tumor boost next to whole-gland EBRT techniques, thereby further increasing the therapeutic efficacy for intermediate- to high-risk disease [14]. Recurrence risk and location Although dose escalation is increasingly adopted, recurrent prostate cancer after pri- mary radiotherapy remains common. A recent series of 2.694 patients treated with doses above 78 Gy revealed 10-year biochemical recurrence risks of approximately 10%, 23% and 44% in low-, intermediate- and high-risk patients, respectively [15]. Bio- chemical recurrences according to the Phoenix definition (i.e. PSA nadir + 2.0 ng/ml) preceded the development of distant metastases and death due to prostate cancer by 5.4 years and 10.5 years, respectively. In patients with a reasonable life-expectancy, management of these recurrences is therefore often necessary to prevent cancer-re- lated complications and mortality. Primary prostate cancer is often a multifocal process [16,17], with a hypothesized ‘index lesion’ driving metastatic potential [18,19]. Within this hypothesis, it is thought that synchronous lesions outside the index lesion are secondary insignificant cancers which lie dormant [20]. After primary whole-gland radiotherapy, several series have shown that recurrences nearly all (89-100%) regrow at the site of the primarily largest and/or highest grade index lesion [21-25]. This indicates that the malignant remnant causes biochemical failure, while secondary indolent tumor foci have been successfully treated by the primary radiation course. Building on this, the rationale behind focal treatment in the localized radiorecurrent setting becomes clear. Although the index lesion hypothesis remains controversial due to a lack of robust evidence, long-term oncological efficacy data of focal treatments in the future might help to either support or undermine this view. Traditional approach to radiorecurrent prostate cancer The treatment of prostate-confined recurrences after primary radiotherapy is called salvage and will be denoted as such in the subsequent part of this review. Within the literature there are reasonably large series available describing the results of salvage treatments directed at the entire prostatic volume. These series include salvage radical prostatectomy (SRP) [26], whole-gland salvage cryotherapy [27,28], whole-gland sal- vage high intensity focused ultrasound (HIFU) [29,30], and in increasingly larger series, whole-gland salvage brachytherapy [31-33]. These studies show an approximate 5-year biochemical failure-free survival (bFFS) of 50-60%, thereby postponing the use of pal- liative ADT with its associated toxicity [34]. However, due to previous radiation damage to organs at risk, toxicity of secondary surgery or radiation can be deleterious. Severe genitourinary (GU) and gastro-intestinal (GI) toxicity, requiring operative intervention to resolve, are observed in about 30% of patients, with erectile dysfunction (ED) often present in 100% of cases post-salvage [35]. For this reason, whole-gland techniques