Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and older men, with a prevalence of >50% in men over 50 years of age and 90% in men over 80 years of age reported in the literature.BPH leads to bladder outlet obstruction, dyspareunia (lower urinary tract obstruction symptoms, LUTS), and eventually bladder and kidney damage. Currently, the main methods of treating BPH are drugs, surgery and microtechnotherapy, all of which have limitations. The drugs used for conservative treatment of BPH are alpha blockers and 5 alpha reductase inhibitors, which can be used alone or in combination to reduce the symptoms of obstruction to a certain extent First-line treatment measures are suitable for moderate lower urinary tract obstruction, but require long-term medication and have certain side effects.
Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly men, with a reported prevalence of >50% in men over 50 years of age and 90% in men over 80 years of age.BPH leads to bladder outlet obstruction, difficulty in urination (lower urinary tract obstruction symptoms, LUTS), and eventually bladder and kidney damage. Currently, the main methods of treating BPH are drugs, surgery and microtechnotherapy, all of which have limitations. Conservative treatment of BPH includes alpha-blockers and 5α-reductase inhibitors, which can be applied alone or in combination and can reduce the symptoms of obstruction to some extent First-line treatment measures are suitable for moderate lower urinary tract obstruction, but require long-term medication and have certain side effects. Surgical resection of the prostate includes open surgery and transurethral resection (TURP). The former is the standard technique for treating BPH with a volume >80-100 g, while TURP is the standard technique for treating BPH with a volume <80 g. The former is the standard technique for treating BPH with a volume <80 g. The former is the standard technique for treating BPH with a volume <80 g. Surgical treatment is effective but more invasive, with problems of longer hospital stays, postoperative pain and discomfort, and a certain rate of complications (urethral infection, urethral stricture, postoperative pain, urinary incontinence, urinary retention, and sexual dysfunction). The clinical application of various minimally invasive techniques, including laser ablation, transurethral microwave ablation, transurethral RFA, and percutaneous transluminal cryopexy/RFA, has been reported more frequently in an attempt to replace traditional surgical treatment and reduce the risk of treatment, and has achieved certain results, but at present, no minimally invasive treatment technique has been proven to be superior to TURP in terms of efficacy, complication rate, economic cost, safety, and other comprehensive assessments.
Prostatic artery embolization (PAE) offers a new option for the treatment of BPH. PAE has been used to a certain extent in Europe and the United States, and is safe, without serious complications or deaths, when the interventional radiologist is fully familiar with the pelvic vascular anatomy and applies appropriate techniques. The results of PAE are considered an important advancement in interventional radiology in recent years, and its therapeutic value and significance are similar to that of uterine artery embolization for the treatment of uterine fibroids, with good prospects for application.
1. About the anatomy of the prostatic artery
One of the key techniques of PAE is to identify the prostatic arteries in order to avoid accidentally embolizing the normal vessels surrounding the prostate (such as the bladder artery, the cavernous artery of the penis and the rectal artery). Most anatomic monographs describe the prostatic arteries as “arising from the cystic artery, the inferior cystic artery, or the internal-rectal pubic artery”. In recent anatomical journal literature, most studies of prostatic arteries are based on the observation of nonprostatic cadaveric specimens, with inconsistent descriptions, including 41.5% from the inferior vesical artery, 26.4% from the internal pudendal artery, 15.1% from the umbilical artery, and 15.1% from the internal rectal artery. artery (15.1%), obturator artery (5.7%), inferior gluteal artery (1.9%), and internal iliac artery (9.4%); other arteries included superior bladder artery and inferior rectal artery. Due to factors such as deformation of the isolated specimen, non-physiological silicone perfusion technique and the small size of the normal prostatic artery, the prostatic artery observed at autopsy is not consistent with the prostatic artery in vivo, especially in the hyperplastic state of the prostate.
Bilhim T et al. of the University of Lisbon, Portugal, did a comparative detailed analysis of 75 cases (all BPH patients intended for PAE) and 150 lateral pelvic arteries using CT-enhanced angiography (CTA) and angiography (DSA) and found that: two and more (2-4) prostatic arteries on one side of the pelvis in 43% of cases and single in 57% of cases; prostatic arteries originated from the internal pubic The prostatic arteries originated from the middle-distal segment of the internal pubic artery in 34.1%, from the common trunk with the superior cystic artery in 20.1%, from the inferior gluteal artery – internal pubic artery trunk in 17.8%, from the occluded artery in 17.8%, and from the common trunk with the inferior rectal artery in 8.4%; rare origins included the inferior gluteal artery in 3.7%, the internal parapubic artery in 1.9%, and the superior gluteal artery in 1.4%. In addition, nearly 60% of prostatic arteries had anastomosing branches with other arterial branches (bladder, rectal, obturator, intrapubic, contralateral prostate, superior/inferior gluteal, and internal parapubic arteries).
The prostatic artery and adjacent arteries were observed in 117 patients (112 BPH, 5 tumors) by DSA, combined rotational angiography and CB-CT (cone-beam CT), and the main differences seen from those reported by Bilhim T were: (1) high origin of the prostatic artery (4.3% directly from the anterior trunk of the internal iliac artery, or 17.1% from the beginning of the internal pubic artery The majority (68.7%) of the prostatic arteries originated directly from the anterior internal iliac artery in 4.3%, or from the beginning of the internal pubic artery in 17.1%, from the beginning of the inferior gluteal-internal pubic artery in 18.2%, and from the superior cystic artery in 29.1%, which corresponds to the level of the inferior border of the sacroiliac joint, which is one of the most characteristic features and a marker for finding prostatic arteries; (2) 25.6% originated from the middle-distal segment of the internal pubic artery, which is significantly lower than that reported by Bilhim T. (3) from the occluded artery (3.0%) and rectal artery (2.7%) were significantly lower than those reported by Portuguese scholars. (4) The frequency of anastomotic branches between the prostatic artery and other arterial branches was related to the pressure of the contrast injection, and the higher pressure of the contrast injection resulted in non-physiological anastomotic branch visualization. Whether these differences in results are due to differences in the method of observation or to differences in ethnicity needs to be further investigated.
Regardless of the differences in the origin of the prostatic arteries, both in vivo and ex vivo studies, the arteries that ultimately supply the prostate (reaching the prostatic margin) have two components (branches): the anterior-lateral branch and the posterior-lateral branch, the former being the vessel supplying the central part of the prostate and the BPH The former is the blood vessel supplying the central part of the prostate and BPH nodes, and is the ideal artery for embolization; while the posterior-lateral branch mainly supplies the peripheral part of the prostate, and can communicate with the rectal-seminiferous artery in the back.
2.Selection of embolization material
There is no consensus on the most suitable embolization material for PAE. Theoretically, all materials that can be used for uterine artery embolization (UAE) for uterine fibroids are suitable for PAE; however, because of the differences in the vascular architecture of uterine fibroids (vessel diameter, density, spiral-like type, etc.) and that of prostatic hyperplasia, PAE should not simply apply the UAE technique.
Currently, Brazilian, Portuguese, American, British, French, and Italian authors report different embolic materials used, ranging from PVA particles (100-200 μm, non-deformable, non-absorbable polyethylene material, represented by Portugal) to polypropylene microspheres or particles of similar material (Brazil: 100-500 μm Embosphere Microspheres [Biosphere Medical, Roissy, France]; USA: 100C400μm Embozene [CeloNova, SanAntonio,Texas]), the latter being soft and deformable. Based on the successful experience with embolization of malignant tumors and hepatic hemangiomas, the basic conditions for obtaining ischemic necrosis of tumors or lesions are: complete embolization of microvessels of the tumor, avoidance of collateral or traffic branch formation, destruction of endothelial cells of the tumor vessels, induction of thrombosis, and avoidance of recanalization. Therefore, the particles for embolization of prostatic arteries should be ≤100 μm in diameter, and the material should be soft and deformable in nature to facilitate filling the entire vascular bed; theoretically, embolization with smaller particles (10-50 μm) may obtain more tissue necrosis, but misembolization of adjacent organs via traffic branches is a matter of concern.
In addition to the size of embolic particles, comparing the efficacy of different types of embolic materials is also a work worthy of attention. It should be emphasized that some materials, although they can be used for intravascular embolization to treat vascular malformations (such as anhydrous alcohol, other vascular sclerosing agents, iodine oil, gum, etc.), should not be used blindly for PAE.
3.About PAE indications
BPH is a common specialty disease, and PAE must be performed with the assistance and support of a urologist, and some of the specialty tests related to BPH (such as IPSS [international prostate symptom score], QOL score [quality of life Some of the specialized tests related to BPH (such as IPSS [international prostate symptom score], QOL score [quality of life assessment, QOL], urinary flow rate peak urinary flow [Qmax] and IIEF score [International Index of Erectile Function], etc.) must be performed by a specialist or a physician with specialized training.
The recommended indications for PAE in Europe and the United States are: age >50 years, moderate to severe symptoms clearly due to BPH (IPSS >18, quality of life score [QoL]>3, urinary flow rate <12 mL/sec, with or without acute urinary retention), ineffective drug therapy for more than 6 months, prostate volume >40 g, and indication for surgical or minimally invasive surgical treatment. Indications for puncture biopsy: clinical examination (fingerprinting), MRI or ultrasound suspicion of prostate cancer, PSA > 4.0 ng/mL. Not recommended: malignant tumors of the prostate or bladder (not an absolute contraindication in those treated with hemostasis or palliative care); large bladder diverticula (> 5 cm), large stones (> 2 cm); renal failure; acute urinary tract infection; neurogenic bladder and forced abnormal urethral function; urethral strictures; uncorrectable coagulation disorders; and other conditions for interventional treatment.
Since there are still many uncertainties about the efficacy of PAE (see later), in addition to the above basic principles, the author emphasizes the following indications and contraindications for PAE: (1) Currently, as a complementary technique, PAE is suitable for patients with significant symptoms, ineffective drug therapy, and unsuitable for surgery or other treatments; (2) PAE is a mature technique for BPH-related bleeding that is ineffective with conservative treatment. (2) PAE is a proven technique for BPH-related bleeding where conservative treatment is ineffective and is also suitable for rich vascularity and surgical treatment of high-risk giant BPH (PAE reduces intraoperative major bleeding complications); (3) the presence of severe atherosclerosis and severe tortuosity of the iliac arteries is not an absolute contraindication to PAE. In addition, symptoms due to BPH include urinary urgency, frequency, increased nocturia, dysuria, urinary incontinence, hematuria, and hydronephrosis, and PAE can benefit or improve those symptoms, which need to be further defined. From our limited experience, the efficacy of PAE on acute urinary retention caused by BPH and obstructive symptoms such as dyspareunia and hematuria is clear.
4. Regarding the evaluation of the efficacy of PAE
Traditionally, subjective (e.g., IPSS, QoL, IIEF) and objective (e.g., urodynamic (Qmax, bladder residual urine volume, pressure parameters, etc.), PSA, prostate volume, etc.) parameters are used to evaluate the efficacy of treatment of LUTS due to BPH, but not all of them are considered effective when improvement is obtained. In clinical practice, 1-3 parameters (e.g. IPSS, QoL, Qmax) are usually selected to evaluate the effectiveness of a particular technique. The patient’s subjective perception after treatment (IPSS, QoL) is generally used as the main evaluation index, while laboratory tests (e.g. PSA) and imaging tests (e.g. ultrasound, MRI) are only used as reference indicators, not essential indicators.
At present, the criteria for evaluating the clinical efficacy of PAE are not consistent, and this is one of the points that the urological community questions about PAE. What parameters or indicators are appropriate for evaluating the efficacy of PAE? There is a need for industry standards that can be accepted. Pisco JM et al, University of Lisbon, Portugal, used subjective indicators (25% reduction in IPSS or total score <18< span=""> points; Qol reduction of at least 1 point or total score ≤3 points). Carnevale FC et al, University of São Paulo, Brazil, defined the indications of clinical success as patients with acute urinary retention who were able to withdraw the catheter and approach normal voiding after PAE; significant improvement in IPSS and QoL, and no significant complications. Bagala S et al. in the United States used the American Urological Association (AUA) scoring system (similar to QoL), and a postoperative reduction of 3 points was considered a clinical success. Recently, the American Interventional Radiology (SIR, JVIR, 2014,25:1349) in its review of PAE mentioned the use of IPSS (subjective index) and Qmax (objective index) as appropriate indicators to evaluate the clinical efficacy of PAE, in line with the recommendations of the European Society of Urology, which is also advocated by the author’s unit.
Regarding the changes in prostate volume after PAE: (1) the prostate volume reduction rate of 15%-40% after PAE (mean about 30%; most <30< span="">%) is much lower than the reduction of the entire uterus (50%-60%) after embolization of uterine fibroids with the same technique, the reasons for which are unclear and suggest the need for further exploration; (2) the literature reports that The improvement of clinical symptoms, urodynamic changes and the degree of prostate volume reduction in patients after PAE are not completely consistent: although there is a clear reduction in prostate volume after PAE but no improvement in symptoms, there is no change in prostate volume after PAE but significant improvement in symptoms; it indicates that prostate volume reduction after PAE is not a single factor in relieving symptoms, other factors such as reduced prostate blood flow (lower hormone levels) after embolization resulting in histological changes in the prostate and changes in tone may affect bladder emptying. For the same reason, it has been suggested that the psychological factors that arise after PAE cannot be ignored (does PAE really work?) , and even the idea of doing a controlled study with placebo versus PAE has been proposed.
5. Technical difficulties and challenges of PAE
(1) There are limitations in the understanding and knowledge of the anatomy of the prostatic arteries. In addition to the controversial origin of the prostatic arteries, it is not clear whether the arteries involved in prostate blood supply are multiple branches or non-physiological traffic branches (open only in pathological conditions).
(2) The presence of more severe atherosclerosis, arterial tortuosity, and stenosis obstruction in elderly patients is one of the main technical difficulties of PAE. About 10% of patients have narrow prostatic artery openings, and the openings are at right angles or even acute angles making super-selective cannulation very difficult.
(3) In about 5-10% of patients, only one side of the pelvic prostatic artery can be found during PAE. This is not a true case of absence or dysplasia of one side of the prostatic artery, but rather a failure to show the prostatic artery because it is too small, severely stenosed, or has a different origin. In this case, unilateral PAE has to be performed, and it has been reported in the literature that embolization of unilateral PAE results in a 52.6% clinical symptom relief rate and a 15% average reduction in prostate volume; however, the experience of the author’s unit is that only about 1/3 of the patients with unilateral PAE had symptom relief after the procedure, and half of them had a recurrence of symptoms to the pre-embolization level within 6 months. Therefore, unilateral PAE cannot be considered a complete technical success (except for cases such as unilateral dominant blood supply and dysplasia of one prostatic artery).
(4) The problem of recanalization (symptom recurrence) after embolization: This is a problem that cannot be ignored to affect the medium- and long-term efficacy. Brazilian scholars reported that the incidence of recurrence of symptoms after PAE is about 5%. The analysis of data from 10 cases of second PAE (8 cases with insignificant improvement of symptoms after the first PAE, 2 cases with recurrence of symptoms 3 or 6 months after the first PAE) revealed that: unilateral embolization (2 cases of failure to find the other prostatic artery for the first time, 2 cases of premature occlusion of one prostatic artery due to entrapment or spasm), although embolization of both prostatic arteries, but missed embolization of one of them The prostatic arteries (all posterior lateral branches, 4 cases) and collateral formation (complete occlusion of the first embolized prostatic artery, appropriate embolization technique, but multiple small collateral branches formed to supply the prostate in 2 cases) were the reasons for the failure of the first PAE. Among them, how to avoid the establishment of side branches supplying the prostate is a focus and difficulty that affects the medium- and long-term efficacy of PAE.
6. Comparison with other treatment methods
(1) What are the advantages of PAE compared with traditional open surgery and TURP? No general or lumbar anesthesia, no urethral route, no bleeding risk, short or even no hospitalization, repeatable treatment, no common complications of traditional open surgery and TURP (urethral stricture, postoperative pain, urinary incontinence, sexual dysfunction) are the advantages of PAE; while low objective efficiency, more factors affecting efficacy, uncertainty of long-term efficacy are the current problems of PAE. (2) Objective comparison of PAE is needed.
(2) Objective comparison of the efficacy of PAE and HoLEP is needed: HoLEP (holmium laser enucleation of the prostate) is considered to be equal to or better than TURP in terms of efficacy, and is characterized by the fact that it is not limited by the size of the prostate (TURP is suitable for those with a volume < 80 mL), and its high efficiency in removing prostate tissue and low complication rate are also advantages of HoLEP. Although PAE is also not limited by the size of the prostate, overall, the larger the prostate and the more abundant the blood supply, the higher the technical and clinical success rate.
(3) Need for comparison with other minimally invasive techniques: Minimally invasive techniques for the treatment of BPH still include percutaneous puncture microwave, radiofrequency, and cryopreservation. The literature reports that various minimally invasive techniques applied in the past have excellent recent efficacy, but about 25% of patients need to receive TURP within 2 years because of the limited time to maintain efficacy after treatment with these minimally invasive techniques. The efficacy beyond 2 years after PAE needs to be observed.
Summary.
Treatment of BPH with PAE is considered one of the important advances in urology and interventional radiology in recent years, and its therapeutic value and significance are considered similar to the use of uterine artery embolization for the treatment of uterine fibroids, but there are still different voices (mainly from the urology community), and there are limits and difficulties in initiating a larger scale of universal application. In the author’s experience, PAE is currently used as a complementary treatment technique, selectively for patients who have failed pharmacological treatment, whose quality of life is affected, who have no indication for surgical treatment, and who are not suitable for other minimally invasive treatments (e.g., TURP, HoLEP, microwave, etc.). From the data reported in the current large sample, even with appropriate application techniques and choice of embolization materials, the degree of prostate reduction after PAE is limited (most about 30%) and the clinical efficiency is 70% to 80%, which differs from the reduction (60-70%) and clinical efficacy (90-95%) of uterine fibroids embolized with the same method; the recurrence of LUTS symptoms, vascularization, and de novo prostate nodules with more than 2 years of follow-up recanalization, and de novo prostatic nodules at more than 2 years of follow-up are also issues of concern.