General introduction and thesis outline 21 Locally recurrent prostate cancer Although recurrence rates after primary prostate cancer are very low in low-risk patients, still up to 50% of the high-risk patients develop a (biochemical) recurrence within 10 years after treatment.73 The management of recurrent prostate cancer remains controversial, as the natural course is very heterogeneous.74 In some patients, the cancer remains indolent for many years, without becoming clinically relevant. In others, the cancer progresses rapidly, causing morbidity and mortality. Generally, biochemical recurrence precedes both progression to distant metastases and prostate cancer-specific mortality.73,75 As with primary prostate cancer, it remains important to weigh the potential benefits and harms of treatment. Nowadays, many patients with biochemical recurrence are still treated with (deferred) ADT.76 However, ADT is a systemic treatment and is associated with significant side effects, such as hot flushes, osteoporosis, loss of libido, erectile dysfunction, and therefore deterioration of quality of life.77 Moreover, tumour progression under hormonal treatment (i.e. castration resistant prostate cancer) usually occurs within 1-3 years after start of hormonal treatment, requiring further systemic treatment with for example second-line hormonal treatment or chemotherapy.29,78–80 Local treatment for recurrent prostate cancer Since after radiotherapy the recurrent lesion (radiorecurrent prostate cancer) is often confined to the prostate, local therapy is an attractive treatment option with the aim of postponing toxic systemic treatment. Various salvage treatment modalities, such as salvage radical prostatectomy, brachytherapy, HIFU, and cryotherapy have been investigated for patients with local, organconfined recurrences.81–84 In the early days, salvage treatment was aimed at treating the entire prostate gland (so-called whole-gland treatment). These treatments were associated with high rates of urinary incontinence, impotence, fistulae, and urethral strictures.85–88 Focal salvage treatment Prostate tumours seem to recur most often at the site of the primary dominant lesion (the so-called index lesion) and are mostly unifocal.89,90 Because of this, focal salvage is an attractive treatment option for patients with a local, intraprostatic recurrence. Due to improved imaging techniques, such as mp-MRI and PSMA-PET/CT, focal treatments have become available over the last two decades. With focal salvage treatment, only a part of the prostate, such as the tumour or the quadrant or hemi-prostate containing the MRI- and PSMA-PET/CT-visible tumour, is targeted. The advantage of focal salvage over whole-gland salvage treatment is the reduced risk of (severe) side effects.82 Due to the lower treatment volume, OARs can be spared more optimally. Multiple focal salvage techniques have been investigated over the last years in – often small and retrospective – single arm cohort studies. Currently, focal salvage treatment is performed using a range of modalities, mostly still within clinical trials. These include brachytherapy91–99, cryotherapy100–106, and HIFU107–110. As the studies often included a small sample size, and because of heterogeneity with respect to inclusion criteria, the results are difficult to compare. Overall, focal salvage techniques seem to have similar outcomes with respect to cancer control when compared to whole-gland 1
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