Outcome after prostatic artery embolization in patients with symptomatic benign prostatic hyperplasia

Abstract

Background

Prostatic artery embolization (PAE) has recently been described as a promising alternative treatment for lower urinary tract symptoms (LUTS) due to an enlarged, benign prostate.

Purpose

To evaluate the safety, morbidity, and functional outcomes after PAE.

Material and Methods

Twenty-nine consecutive patients were included. All patients had computed tomography angiography before the procedure. Microcatheters were used for selective embolization of the PAs. Large side branches to non-target organs were embolized with coils. The PAs were embolized with calibrated 300–500 µm tris-acryl gelatin microspheres. Complications were recorded before discharge. Clinical visit was performed after three months, magnetic resonance imaging (MRI) after 6–12 months, and any further intervention recorded in the chart. Mean follow-up was 23 months. Clinical success was defined as no longer needing urinary catheter, no long-term complications, and no need of further interventions.

Results

Sixteen patients (55%) had permanent or intermittent catheter before the procedure. Bilateral embolization was performed in 26 patients (90%). Five patients underwent two procedures. Twelve of 16 patients (75%) with permanent or intermittent catheter were able to remove the catheter. Five patients were operated with transurethral resection of the prostate (TURP). Except for one patient, all patients without catheter at baseline improved in the International Prostate Symptom Score (IPSS) and had no further treatment. Twelve patients experienced complications; all were grade 1 according to the Clavien–Dindo classification.

Conclusion

PAE reduced LUTS symptoms in most patients without severe complications. The treatment did not exclude additional surgical treatment when needed.

Keywords

Benign prostatic hyperplasia prostatic artery embolization CT angiography adverse events

Introduction

Population-based studies suggest that 14% of men in their 40s and > 40% of men aged > 60 years have benign prostatic hyperplasia (BPH) (1). Lower urinary tract symptoms (LUTS) are common complaints secondary to BPH and consist of hesitancy, weak stream, straining, feeling of incomplete bladder emptying, frequency, intermittency, urgency, and nocturia. LUTS severity is most commonly evaluated by means of the International Prostate Symptom Score (IPSS): mild LUTS (IPSS 1–7); moderate LUTS (IPSS 8–19); and severe LUTS (IPSS 20–35). When LUTS are refractory to medical therapy, TURP and open prostatectomy are the historical reference-standard surgical procedures for prostates with volumes < 80 mL and ≥80 mL, respectively (2). Both procedures offer lasting improvements in urinary functional outcomes but have the potential for considerable perioperative complications and morbidity (3 –5) and carry significant healthcare costs (6). Following surgery, the majority of men will experience retrograde ejaculation after both treatments. Other important short-term side effects are risk of bleeding and need of transfusion in 8–27% and urinary tract infections. The most important long-term side effects are incontinence (3–6%), erectile dysfunction (10%), stricture, and need for a secondary procedure (5–14%) (3 –5). Mandal et al. reported an association between Charlson co-morbidity index (7), large prostate volume, extended operative time, and duration of hospitalization in men who underwent TURP (5). Open prostatectomy is a more invasive and resource-demanding surgical procedure than TURP, with significant rates of complications and extended periods of hospitalization. Prostatic artery embolization (PAE) has recently been described as a promising, minimally invasive alternative treatment for LUTS due to an enlarged, benign prostate (8 –11). Several recent reports describe PAE as a safe and promising minimally invasive method as a supplement to TURP and transvesical open prostatectomy for treatment of symptomatic BPH in patients with large prostates (12 –14). Few complications have been reported (15,16) and clinical results are promising also when compared to TURP and open prostatectomy (17 –20). PAE is performed under local anesthesia through a vascular access sheath inserted in the common femoral artery (21 –23). Small particles are injected through microcatheters directly into the arteries supplying the prostate. The main challenges are variation in arterial anatomy, the small size of the arteries, side branches to vital organs in the pelvis, and arterial atherosclerotic disease. The purpose of this study was to evaluate safety, morbidity, and functional outcomes of PAE in men suffering from LUTS secondary to BPH.

Material and Methods

This is a prospective single-center observational study. Twenty-nine consecutive patients suffering BPH-related LUTS between December 2015 and March 2017 were included. Inclusion criteria were men presenting with moderate to severe LUTS and evidence of urinary retention or bladder outlet obstruction as assessed by measurements of post void residual volume and performing cystometry and uroflowmetry (24). LUTS had to be refractory to medical treatment for at least six months or the patient was unwilling to accept medical treatment. All participants were able to provide signed informed consent. Prostate volume should be > 80 mL or > 30 mL if the patient was unfit for surgery or declined proposed TURP due to risk of side effects. Exclusion criteria included urological disorders, suspected prostate cancer, prostatitis, detrusor-sphincter dyssynergia, evidence of neurogenic bladder, urethral strictures, bladder neck contracture, bladder stone, or bladder cancer. We also excluded renal insufficiency defined as GFR < 50 mL/min/1.73m² and known allergic reactions to iodine-based contrast or gadolinium-based contrast.

All patients had magnetic resonance imaging (MRI) of the prostate to exclude prostate cancer. Computed tomography angiography (CTA) of the pelvic arteries was performed to evaluate atherosclerotic disease and arterial supply to the prostate. Anatomy was evaluated in the Syngo.Via software (syngo.via, version VA20, Siemens Healthcare). An indwelling urinary catheter was placed before the PAE procedure unless the patients already had permanent catheter (25). In the angio suite ampicillin 2 g was given i.v. and diazepam 2.5–5 mg i.v. was given on demand. The right femoral artery was the preferred access site and 6F sheath was placed into the artery (Destination RDC 45 cm, Terumo Interventional Systems, Leuven, Belgium). A 5F 65 cm diagnostic catheter was placed into the hypogastric artery ipsilateral and contralateral and a microcatheter was placed into the PAs (Progreat 2.0 or 2.7, Terumo Interventional Systems, Leuven, Belgium). Bilateral embolization was planned from one single femoral puncture. The tip of the catheter was placed to avoid particles into the bladder arteries. Large side branches to non-target organ were embolized with coils (Cook Medical, Bloomington, IN, USA). When flow to the prostate was ceased, the catheter was further advanced as close to the prostate as technical possible (25,26). Particles used were calibrated 300–500 µm tris-acryl gelatin microspheres (Embosphere; Merit Medical, South Jordan, UT, USA). Angioseal (St. Jude Medical, Minneapolis, MN, USA) was used for femoral hemostasis and the patient had bed rest for 2 h after the procedure. The Foley catheter was removed the same evening for all the patients with intermittent catheterization and no catheter before. Removal of permanent catheters was attempted after 14 days.

Acute angiographic success was recorded as either unilateral or bilateral. Complications were recorded before discharge and at clinical follow-up. Clinical visit was performed after three months. Patients with more than one procedure had the same follow-up after the last procedure. Possible needs for catheter and further intervention with TURP were checked in the chart after a mean of 23 ± 5 months (range = 16–32 months). MRI was performed after six months (12 months in one patient). Clinical success was defined as no further need of a urinary catheter, no long-term complications, no need of further interventions. PAE was considered to have failed when the patient later needed a permanent or intermittent catheter or further intervention with TURP. Complications were recorded according to the Clavien–Dindo classification system (27). The continuous variables are described using the mean ± standard deviation and ranges.

The study was approved by the regional ethical committee (2016/360) and the Data Protection Official for Research at the hospital.

Results

Twenty-nine patients were included (mean age = 69 years, age range = 54–86) (Table 1). Sixteen patients (55%) had permanent or intermittent catheters. Bilateral embolization was performed in 26 (90%). Five patients underwent two procedures (Table 2); one repeat bilateral embolization, three separate procedures of the two sides, and one who was initially embolized had bleeding after the following TURP. Unilateral embolization was performed because of stenosis in two and unilateral PA in one. The CTA showed that the origin of the PA was from the inferior epigastric artery in six patients (21%) on one side. The other PAs originated from branches of the hypogastric arteries. MRI-based prostate size before embolization was larger for the patients with permanent catheter (205 ± 100 mL) than the patients using intermittent catheter (85 ± 40 mL) and the patients with no catheter (95 ± 47 mL).

Table 1.

Pretreatment patient characteristics.

	n	Mean	SD	Range
Age (years)	29	69	8.0	54–86
Prostate volume (mL)		127	84	33–405
Permanent catheter	9
Intermittent catheter	7
No catheter before	13
IPSS		25.1	4.8	16–33
Peak urinary flow rate (mL/s)		6.9	3.2	2.3–14.5
Postvoid residual urine (mL)		146	115	0–384

IPSS, International Prostate Symptom Score.

Table 2.

Angiographic and embolization data.

Patients (n)	29
Procedures (n)	34
Bilateral (n (%))	26 (90)
Unilateral (n (%))	3 (10)
Coil embolization (n (%))	8 (28)
Angioseal for hemostasis	All
Time in angio suite (min)	126 ± 40, range 45–220
Fluoroscopy (min)	41 ± 18, range 10–75

MRI showed reduction in prostate size after embolization from 127 ± 84 mL (range = 33–405 mL) to 97 ± 61 mL (range = 34–258 mL). The reduction was the same for patients with permanent catheter, intermittent catheter, and no catheter. Clinical success was obtained in 23 patients (79%). Five patients were operated with TURP and one patient continued with intermittent catheter. The non-responders had the same prostate size as the whole group. Twelve of 16 patients with permanent or intermittent catheter (75%) were able to remove the catheter and no further treatment was necessary (Table 3). Unilateral embolization in three patients was successful in one. Repeat bilateral embolization did not improve the outcome.

Table 3.

Clinical results.

	Before	After	TURP after*
Patients with catheter (n)	16	4	4
Permanent catheter (n)	9	2	2
Intermittent catheterization (n)	7	2	2
Patients without catheter (n)	13		1
IPSS, mean ± 1 SD	25.1 ± 4.8	12.1 ± 7.4
Peak urinary flow rate (mL/s)	6.9 ± 3.2	10.2 ± 3.3
Postvoid residual urine (mL)	146 ± 115	86 ± 62

*Underwent transurethral resection of the prostate after embolization.

IPSS, International Prostate Symptom Score.

Twelve patients experienced complications. The complications were all grade 1 according to the Clavien–Dindo classification system. The minor complications included urinary tract infection (n = 4), temporary pelvic pain (n = 6), post embolization syndrome (n = 2), rectal bleeding (n = 3), and temporary discoloration of the glans penis (n = 2).

Discussion

This is a prospective, single-center study of the early experience with embolization of the PAs in 29 patients to treat LUTS from BPH. Twenty-three patients (79%) improved after 1–2 embolizations and no further intervention was required. Our findings are in accordance with previous studies (8 –11). In this initial study we included many patients with either permanent catheter or intermittent catheter. The success rate was high, 12 of 16 (75%), and comparable to other studies. In one study by Rampoldi et al. (28), an 80% success was achieved. Looking at those patients with no catheter beforehand, all but one patient improved, and no further intervention was needed. In this patient group, the significant reduction in IPSS may better evaluate the outcome of the PAE. Various endpoints have been used to evaluate the clinical effect of PAE. These include relief of acute urinary obstruction, significant IPSS reduction, improved quality of life, increase in urinary peak flow rate, and prostate volume reduction. Repeat embolization is possible when particles are used. We did re-embolize one patient, but the symptoms were not relieved. Previous studies have presented results from re-embolization (29,30). However, the long-term clinical results were < 50% (29). In our report, not all patients improved sufficiently, but importantly, the PAE did not prevent subsequent TURP treatment.

The results of PAE may be inferior to TURP regarding effects on the urinary obstruction and reduction of IPSS. However, PAE has few and minor complications. This is in accordance with our early experience. All complications were grade 1 in the Clavien–Dindo classification system. Post embolization syndrome is a known complication and is probably more frequent in large prostates (13,28). After initial experience with pelvic pain in one patient with a large prostate, we decided to split the procedure into one side at the same time in two patients with prostate volumes 127 and 255 mL. The patients did well after this approach. However, we do not know whether this approach may help in general. Two patients experienced discoloration of the glans penis. Both healed well after a few weeks. This complication may be related to particles entering the pudendal artery or the permanent occlusion of the pudendal artery. Coil embolization of the common pudendal artery was performed in five patients to prevent this complication and one of these experienced the penis problem. Serious complications from particles into non-target organs are possible, but very few have been reported so far (11,29). The number of urinary tract infections in four patients was probably related to the high number of permanent catheters used previously (3/4).

Anatomic variants as well as atherosclerotic arterial disease are important factors to consider when selecting patients for PAE and planning the procedure (21,28). CTA of the pelvic arteries was performed with a slice thickness of 1 mm and reconstructed in three planes, as well as 5 mm maximum intensity projection (MIP) and volume rendering (VR) images. The CT was helpful in detecting the number of Pas and the origin and optimal angulation during intubation of the PAs. We did not use CT to exclude patients with tortuosity of the pelvic arteries, but the procedure lasted longer for these patients. Some PAs were difficult to visualize and were better seen at CTA after NG injection. We did not embolize all PAs. Some arteries were too small for selective injection even after the nitroglycerin 200 µg injection and were abandoned from embolization. The common trunk to the urinary bladder with multiple small branches was also not embolized. Many patients had arterial supply to the prostate from the inferior epigastric arteries. The number of PAs from the inferior epigastric artery was higher in our study compared to the anatomical study of de Assis et al., with 6/58 arteries (10% vs. 0.35%) (31).

Particles of various sizes and types of polyvinyl alcohol, non-spherical and spherical, have been used in PAE. We used spherical Embospheres 300–500 µm. Previous studies used smaller particles (13,18,29,32) and some used the same size as we did (25,29,32). We do not have any preference of particle choice. The PAs are normally small and peripheral embolization is required. However, there is an increased risk of small particles since it is difficult to completely avoid non-target embolization in this area. Bleeding from the urinary bladder and the rectum both underline this problem. When embolizing with particles, the microcatheters should be small enough to let the blood flow pass the catheter in the PA. Initially we used 2.7-F catheters but recognized that 2.0-F better preserved PA flow with the catheter in place. Having well-diluted particles, the small catheter did not occlude. Nitroglycerin given i.a. before injection of particles improved the size of the PA. In addition, replacement of the particle fluid with nitroglycerin further improved the size in the very small PAs.

Several other less invasive therapies have been made popular in the past two decades, including photo selective vaporization of the prostate, transurethral needle ablation, transurethral microwave therapy, and holmium laser enucleation of the prostate. The most promising results have been produced with the laser therapies, which achieve similar results to those of TURP, but with fewer complications and side effects (33,34). Data on long-term efficacy of these new therapies are lacking (35). Patients eligible for PAE are probably the same patients that presently undergo TURP or open prostatectomy in case of large prostates.

In conclusion, the initial results are good with few side effects and the treatment does not prevent additional treatment when needed. PAE is a day procedure. Our ambition is to proceed with a prospective randomized study of PAE versus TURP.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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