Author(s):
Jonathan Wakim
Perelman School of Medicine ’23

Triet Do
Tulane School of Medicine ’22

Caitlin Smith
Touro School of Medicine ’24

Pascal Acree
Medical College of Georgia ’24

Akshita Pillai
UTMB School of Medicine ’22

History
Benign prostatic hyperplasia (BPH) is a common condition in men over the age of 60 that can cause symptoms such as urinary urgency, nocturia, decreased urinary flow rates, hesitancy, and incomplete bladder emptying. Effective treatment of BPH is important in order to improve quality of life and prevent complications such as bladder stones, urinary tract infections, and damage to the bladder. Recently, prostatic artery embolization (PAE) performed by an interventional radiologist has been approved as a safe, minimally invasive treatment option to alleviate symptoms secondary to BPH.1

Transcatheter arterial embolization for urologic disease was first reported in 1976 by Mitchell et al for managing severe hematuria due to uncontrollable bleeding from the bladder or prostate when all other measures were unsuccessful.2 This technique involved embolization of bilateral internal iliac arteries to treat the life-threatening bleeding. This technique has since evolved to more selective catheterizations of specific internal iliac branch arteries with the development of microcatheters. The benefit of PAE was first discovered in 2000 by DeMeritt et al when the authors embolized the right inferior vesical artery until complete devascularization of the prostate. This resulted in a reduction of prostate volume by 40% and a decrease in the patient’s urinary tract symptoms.3 In 2015 de Assis et al treated 35 patients with BPH using PAE and observed a significant reduction in urinary tract symptoms and prostate volume with no major complications reported.4

Currently, moderate to severe symptoms resulting from BPH are commonly treated either pharmacologically, or with prostate surgery. Pharmacologic therapy commonly includes α-adrenergic blockers, 5α-reductase inhibitors, or muscarinic receptor antagonists.1 These drugs are effective but can be associated with many side effects including dry mouth, blurred vision, tachycardia, urinary retention, constipation, erectile dysfunction and delirium.5 Transurethral resection of the prostate (TURP) is regarded as the surgical gold standard for BPH, however this procedure may result in complications including acute urinary retention, retrograde ejaculation, urinary tract infection, bladder neck stenosis, erectile dysfunction, and bleeding.1 In contrast to surgical treatments, PAE has the advantages of being a minimally invasive, outpatient procedure with a low risk of major complications and shorter recovery time. Current data is very promising for PAE, but further studies are required before it becomes a part of standard-care-treatment for BPH.

Current Indications
PAE is a minimally invasive treatment option for men with symptomatic BPH. Constriction of the urethra due to BPH can cause symptoms including bladder obstruction and lower urinary tract problems (frequency, urgency, nocturia, weak urinary stream, urinary tract infections and bladder stone disease). A pre-procedural workup is required for patients undergoing PAE. This includes measuring baseline prostate specific antigen (PSA) and a full urologic clinical evaluation. Patients complete questionnaires to quantify their baseline urinary and erectile function.Urodynamic testing is done to evaluate the extent of bladder obstruction, the maximum urinary stream and the contractile capability of the bladder. Prostate biopsy or imaging studies with CT/MRI can be obtained based on a case-by-case basis⁶.

PAE is a procedure in which embosphere particles are used to occlude the prostatic artery. The prostatic artery usually arises from the anterior division of the internal iliac artery. However, prostatic artery size and origin differs among patients and even between the right and left side of an individual.. Furthermore collateral vessels from adjacent pelvic organs can anastomose with the prostatic artery, or extraprostatic vessel supply may also be present⁶. Thus, knowledge of the patient’s vascular anatomy is important in identifying the prostatic artery as well as preventing non-target embolization. Intraprocedural cone beam CT (CBCT) is used in conjunction with digital subtraction angiography (DSA) to target both prostatic arteries and to identify accessory or collateral supplies⁶. Embolization of PAE is pressure-dependent due to the small arterial caliber. High injection pressures can increase likelihood of reflux and nontarget embolization. Therefore, slow controlled embolization with diluted particles is performed⁶.

Due to contrast use, poor renal function can be an excluding factor for PAE determination. Atherosclerotic or tortuous vessels of the prostate are also contraindications.  Patients with previous pelvic radiotherapy, bladder calculi, or diverticulae are also not suitable for PAE.7 The need for prostatic biopsy is not addressed with PAE and requires an additional procedure.

Acute urinary retention occurs in roughly one-fourth to a third of patients following PAE. Post-PAE syndrome is the most common complication occurring in ~9% of patients and includes perineal pain, nausea/vomiting, and dysuria. Puncture site hematomas are of low incidence (<1%) and this risk is much less than that of trans-urethral resection of the prostate (TURP).7 Prophylactic antibiotics are administered to decrease the incidence of urinary tract infection following PAE.

Future Directions
TURP is currently considered the standard surgical treatment for BPH and generally results in immediate improvement of bladder obstruction. However, TURP can cause lifestyle-limiting side effects such as urinary stricture, retrograde ejaculation and erectile dysfunction. Additionally, TURP requires significant operative time and hospitalizationFor these reasons, PAE has emerged as an attractive option due to its endovascular approach with a beneficial side effect profile. Current evidence demonstrates that PAE maintains sexual function and ejaculation, but is shown to be less effective in terms of functional outcomes such as maximum urinary flow, post void residual, and reduction of prostate volume.8 However, it should be noted that some of these outcomes, especially differences in quantified urodynamics, are of questionable clinical relevance. Furthermore, although relief of obstruction has been shown to be inferior to TURP in comparative studies, PAE has advantages over TURP in treating patients on anticoagulation or large glands (over 100 cc).9 There are significantly fewer adverse events occurring in patients undergoing PAE versus TURP, namely hematuria, UTI, irritative voiding symptoms, and urethral strictures. PAE has also been shown in cost analyses to be associated with significantly lower direct in-hospital costs and shorter hospital stay. Disadvantages of PAE include longer time for symptom relief, need for ionizing radiation and iodinated contrast, and the rare events of non-target embolization causing, for example, rectal or bladder ischemia. Current research is investigating the effectiveness of PAE using different materials such as HydroPearl beads versus medication for treatment of BPH, exploring ways to reduce the postembolization syndrome in men undergoing PAE, and evaluating PAE for treatment of BPH in larger prostate glands. More high-quality studies such as well-designed randomized controlled trials and meta-analyses of randomized controlled trials are necessary to definitively evaluate and compare efficacy of treatment for BPH. Furthermore, larger-scale studies and longer follow-up periods are necessary to explore long-term effects of this intervention, as well as define the indication for PAE in treatment of BPH.

Current applications have focused on utilizing PAE for treatment of BPH; however PAE is also being considered for intractable prostatic bleeding, similar to management of splenic rupture, epistaxis, or postpartum hemorrhage. Refractory bleeding often occurs in the setting of prostate cancer or post-operative or traumatic bleeding. Current studies show success in control of bleeding, with minor complications ranging from 10-50% and recurrence of hematuria ranging from 10-57%. Though most of the data has been retrospective, heterogenous, or studied in case series, the procedure currently appears safe with low risk of complications and accomplishes technical and clinical success, especially in patients who are poor candidates for surgical intervention.10,11

The true paradigm shift lies in the successful development of a transarterial embolization procedure capable of directly treating prostate cancer (PCa). Such a procedure would need to be technically feasible, safe, and effective at palliating or treating some subset of prostate cancer patients. Pisco et al have demonstrated in a single-center prospective cohort study that prostatic artery chemoembolization (PAC) may be a viable management option for men with prostate cancer. Although the study sample size is small with only 20 patients, the authors show that both safety and periprocedure morbidity are acceptable. In addition, most treated patients experienced a biochemical response and a trend toward improved quality of life.12

Assuming future studies can demonstrate a benefit in delaying PCa progression, men with localized disease and weary of active surveillance can choose prostate cancer chemoembolization as an initial option and not exclude curative therapy (eg, surgery or radiation) at a later date. Through choosing PAC initially, the side effects of definitive treatment (eg. urinary incontinence, erectile dysfunction, radiation effects to bladder and rectum) are diminished or possibly never experienced. In patients with locally advanced disease, PAC may delay the need for androgen deprivation therapy and consequently the side effects associated with castrate levels of testosterone (eg, fatigue, hot flashes, depression, changes in body composition, cardiovascular decline). Finally, in men with locally advanced or metastatic disease (especially men with castrate-resistant PCa), PAC can control the local symptoms of advanced cancer (eg, gross hematuria, lower urinary tract symptoms, bladder outlet obstruction, ureteral obstruction and hydronephrosis) and drastically improve a patient’s quality of life from a palliative perspective.13 However, larger prospective studies are needed to demonstrate the utility of PAC in PCa management and, specifically, to identify men most likely to benefit. More importantly, the effect and potential risks based on disease stage need to be ascertained. Only then can PAC become a recognized management option for men with PCa.

Another recent development with potentially significant future implications is intra-arterial delivery of Y-90 microspheres to deliver high-dose radiotherapy to prostatic tissue to treat locally advanced prostate cancer. Led by Dr. Sam Mouli of Northwestern University, a team of researchers utilized an animal model previously used to establish the basis of PAE and safety for BPH treatment. The team looked to show technical delivery and safety of Y-90 microbeads to prostatic tissue. The team delivered escalated doses of Y-90 microspheres and looked at any postoperative complications in the subsequent three months. Imaging follow-up demonstrated prostate reduction in a dose-dependent fashion starting at two weeks post-embolization and continuing to three months post-therapy, when compared to the untreated contralateral side. The investigators report no clinical adverse events or evidence of nontarget embolization or of any radiation damage to the surrounding bladder, rectum, and erectile tissues on MRI and pathologic analysis. The team is hoping to push this promising work into a clinical trial to bring Y-90 as a potential treatment modality to patients with BPH.14

Alternatives to transarterial embolotherapy for prostate cancer and BPH include transperineal or transrectal thermal ablative techniques, such as cryotherapy, laser therapy, high-intensity focused ultrasound (HIFU), steam ablation (REZUM), and mechanical BPH decompression (UroLift). These techniques provide similar results to PAE and are generally shorter outpatient procedures accomplished without radiation (guided by ultrasound, cystoscopy or MRI). As with PAE and PAC, percutaneous ablations are recent innovations requiring validation and comparison with existing techniques.

References:
1. Yu, H., Isaacson, A., & Burke, C. (2016, September). Review of current literature for prostatic artery embolization. Retrieved March 13, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005086/
2. Mitchell M E, Waltman A C, Athanasoulis C A, Kerr W S Jr, Dretler S P. Control of massive prostatic bleeding with angiographic techniques. J Urol. 1976;115(6):692–695.

3. DeMeritt J S, Elmasri F F, Esposito M P, Rosenberg G S. Relief of benign prostatic hyperplasia-related bladder outlet obstruction after transarterial polyvinyl alcohol prostate embolization. J Vasc Interv Radiol. 2000;11(6):767–770

4. de Assis A M, Moreira A M, de Paula Rodrigues V C. et al.Prostatic artery embolization for treatment of benign prostatic hyperplasia in patients with prostates > 90 g: a prospective single-center study. J Vasc Interv Radiol. 2015;26(1):87–93.

5. Yu, Z., Yan, H., Xu, F., Chao, H., Deng, L., Xu, X., . . . Zeng, T. (2020, May 8). Efficacy and side effects of drugs commonly used for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Retrieved March 13, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225336/

6. Mouli S, Hohlastos E, Salem R. Prostate Artery Embolization. Semin Intervent Radiol. 2019;36(2):142-148. doi:10.1055/s-0039-1688431

7. Maclean D, Maher B, Modi S, et al. Prostate artery embolization: a new, minimally invasive treatment for lower urinary tract symptoms secondary to prostate enlargement. Ther Adv Urol. 2017;9(8):209-216. Published 2017 Jul 10. doi:10.1177/1756287217717889

8. Russo GI, Kurbatov D, Sansalone S, Lepetukhin A, Dubsky S, Sitkin I, Salamone C, Fiorino L, Rozhivanov R, Cimino S, Morgia G. Prostatic Arterial Embolization vs Open Prostatectomy: A 1-Year Matched-pair Analysis of Functional Outcomes and Morbidities. Urology. 2015 Aug;86(2):343-8. doi: 10.1016/j.urology.2015.04.037. Epub 2015 Jul 18. PMID: 26199151.

9. Abt D, Hechelhammer L, Müllhaupt G, Markart S, Güsewell S, Kessler TM, Schmid HP, Engeler DS, Mordasini L. Comparison of prostatic artery embolisation (PAE) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia: randomised, open label, non-inferiority trial. BMJ. 2018 Jun 19;361:k2338. doi: 10.1136/bmj.k2338. PMID: 29921613; PMCID: PMC6006990.

10. Zumstein V, Betschart P, Vetterlein MW, Kluth LA, Hechelhammer L, Mordasini L, Engeler DS, Kessler TM, Schmid HP, Abt D. Prostatic Artery Embolization versus Standard Surgical Treatment for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis. Eur Urol Focus. 2019 Nov;5(6):1091-1100. doi: 10.1016/j.euf.2018.09.005. Epub 2018 Oct 3. PMID: 30292422.

11. Stężewska A, Stężewska M, Żabicki B, Salagierski M. The application of prostate artery embolization in the management of intractable prostate bleeding. Cent European J Urol. 2020;73(3):328-335. doi:10.5173/ceju.2020.0149

12. Pisco J, Bilhim T, Costa NV, Ribeiro MP, Fernandes L, Oliveira AG. Safety and Efficacy of Prostatic Artery Chemoembolization for Prostate Cancer-Initial Experience. J Vasc Interv Radiol. 2018 Mar;29(3):298-305. doi: 10.1016/j.jvir.2017.10.013. Epub 2018 Jan 17. PMID: 29352696.

13. Culp SH. Prostatic Artery Chemoembolization-A Viable Management Option for Men Diagnosed with Prostate Cancer? J Vasc Interv Radiol. 2018 Mar;29(3):306. doi: 10.1016/j.jvir.2017.11.006. PMID: 29455873.

14. https://podcasts.apple.com/us/podcast/ep-78-is-radioembolization-future-option-for-prostate/id1448283964?i=1000489017607