Prostatic Artery Embolization: A Potential Treatment Option for Localized Prostate Cancer

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two common problems in aging men, and pose increasing concerns in health care and social burden as the population ages. In the United States, PCa accounts for over one-quarter of newly diagnosed cancers in men and ranks as the second leading cause of cancer-related death; it is estimated that one in twelve men died of cancer is due to PCa in 2016 [1]. During the past decades, numerous emerging techniques characterized by minimal invasion in the management of BPH and/or PCa have gained in popularity worldwide, including cryosurgery, high-intensity focused ultrasound (HIFU), radiofrequence ablation, microwave therapy , IRE, and photodynamic therapy etc. More recently, prostatic artery embolization (PAE) has showed promising results in animal experiments and clinical practice in relieving lower urinary tract symptoms (LUTS) in patients with BPH. Transcatheter arterial embolization of the prostate has long been used since 1970s to stop bleeding after prostate needle biopsy or transurethral prostatectomy and for intractable gross hematuria of prostatic origin [2]. In 2000, DeMeritt et al. [3] first reported superselective PAE by the use of coaxial microcatheter and polyvinyl alcohol particles to embolize prostatic artery in a BPH patient with severe gross hematuria, requiring a blood transfusion. Not surprisingly, bleeding was immediately terminated even though PAE had been performed only on one side of the prostatic artery; however, the patient reported significant relief in LUTS, the prostate shrank and PSA decreased remarkably during 6-month follow ups. The anecdotal findings revealed a potential therapeutic option in the management symptomatic BPH. Ever since Sun et al. first published an animal experimental study that confirmed the technical feasibility, efficacy, and safety of PAE for the treatment of BPH in 2008 [4], PAE attracted much academic attention and underwent its rapid translation from bench research into clinical practice [5]. In 2010, Carnevale et al. [6] reported successful application of PAE as primary treatment in 2 patients with acute urinary retention due to BPH. Subsequently, Pisco et al. [10] published their clinical series of PAE in the management of symptomatic BPH [7]; in the same year, Sun et al. [8] reported their animal experiments in a canine model revealing technical efficacy of PAE and suggesting its potential application in patients with localized PCa. Up to now, approximately 2000 patients with BPH have undergone PAE worldwide. As indicated in an official position statement of Society of Interventional Radiology, PAE for BPH is a novel and promising therapy that appears safe and efficacious with high patient satisfaction and low repeat intervention rates [9]. The major rationale of PAE behind its therapeutic effects is to destroy targeted tissue in the prostate by creating local devascularization. During the procedure of PAE, a microcatheter is selectively inserted into the prostatic arteries, through which micro particles are injected to occlude small precapillary arterioles, thus inducing irreversible ischemic injury. This peripheral embolization yields extensive and complete intraprostatic ischemia (anoxia), directly resulting in ischemic necrosis or infarction and associated inflammatory reactions, including cytotoxic edema and leukocytic infiltration [2]. Apart from ischemic necrosis, apoptosis is another important pathologic mechanism behind PAE-induced prostate ablation. In general any event that can result in necrosis by cell destruction can induce apoptosis. The hypothesis of ischemia-induced apoptosis is supported by previous experiments in rats and dogs, and clinical observation in BPH patients during follow-ups after PAE [2]. More importantly, androgen-related apoptosis behind PAE is of great clinical implications. The pivotal effects of androgens to development and growth of the normal prostate, as well as pathogenesis of BPH or prostate cancer, depend on a functional androgen-signaling axis. The major components of the axis include: 1) testosterone synthesis, 2) conversion of testosterone to DHT outside and inside of the prostate, 3) transport of testosterone and DHT to target tissue, and 4) binding of DHT to androgen receptor with consequent modulation of the expression of genes and secretion of growth factors that control cellular proliferation and apoptosis [2]. Therefore, interventions in blockage of the androgen-signaling axis at any point would Prostatic Artery Embolization: A Potential Treatment Option for Localized Prostate Cancer