Introduction

Individuals with spinal cord injury (SCI) develop neurogenic bladder due to alteration of the neurogenic control of both the storage and the voiding phases [1]. In case of upper motor neuron lesions, urodynamic evaluation usually documents neurogenic detrusor overactivity with or without detrusor-sphincter dyssynergia. First line treatment for this condition typically includes antimuscarinic therapy to support a low-pressure filling phase and allowing the voiding with intermittent catheterization (IC) without any involuntary urine leakages [2]. When this approach fails, the use of detrusor injections of botulinum toxin-A or nerve stimulation (e.g., sacral neuromodulation, sacral anterior root stimulation) may be employed successfully [3]. In case of patients with detrusor areflexia due to injury of lower motor nerves, IC alone is usually the preferred method for bladder management [2, 4].

The life expectancy of people with SCI is increasing thanks to medical advances, and old men are frequently experiencing difficulties during IC because of benign prostatic hyperplasia (BPH) [5]. This age-related phenomenon results in a large prostate with subsequent compression of the prostatic urethra, increasing the risk of urethral trauma, macrohematuria and urinary tract infection (UTI) during IC [6].

Individuals with SCI who do not urinate may avoid a complete prostate adenoma removal that could be associated with severe complications in favor of the creation of enough space in the prostatic urethra to allow an easy and safe catheter passage. Therefore, a minimally invasive approach to reduce prostate volume (PV) and ease IC is warranted in spinal cord inured patients, especially considering their frailty. Over the last years, prostatic artery embolization (PAE) emerged as an effective technique associated with minimal morbidity to treat BPH [7,8,9,10].

The aim of our study was to assess the feasibility, safety and efficacy of PAE for reducing PV in patients with SCI who experienced difficulties with IC due to concurrent BPH by a tertiary referral center for SCI.

Methods

We retrospectively collected data from all patients followed by our tertiary referral center, the Unit of Neuro-Urology—Unipolar Spinal Unit, Niguarda Hospital, Milan, Italy. In January 2021, we considered all patients with SCI who underwent PAE from January 1st, 2015, to December 31st, 2020. All study phases followed the principles outlined in the Declaration of Helsinki and all applicable institutional and governmental regulations.

We included the following pre-procedural data: neurological level of SCI, age at PAE, antithrombotic therapy, and bladder management (indwelling urinary catheter [IDC] versus IC, and use of muscarinic receptor antagonist [MRA]). Before the procedure, all patients underwent multiparametric magnetic resonance imaging (mpMRI) of the prostate following the criteria of Prostate Imaging-Reporting and Data System version 2 [11]. In this way, we excluded the presence of suspected prostate neoplasms and estimated the PV using T2-weighted coronal and sagittal images (Fig. 1). We repeated mpMRI after about 6 months since PAE to estimate the PV and its percentage decrease.

Fig. 1: Pre-procedural prostate multiparametric magnetic resonance imaging (mpMRI) of Case n°7.
figure 1

The mpMRI allows to evaluate prostate volume (114 ml) and pelvic vessel anatomy in order to plan the prostatic artery embolization.

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We screened for procedure time, intra- and post-procedural complications. The length of stay was not comparable, as some patients stayed more than necessary by our Unit for other medical reasons (e.g., treatment of pressure ulcers, training for trans-anal irrigation, rehabilitation program). In case of patients with IDC, we started IC after 15-30 days depending on visit availability. We collected data about the bladder management after PAE, which was established following post-procedural videourodynamics.

Procedural description

Patients received 400 mg intravenous ciprofloxacin prior to the procedure, and 500 mg oral ciprofloxacin twice per day for one week following the procedure.

All PAE procedures were performed by a group of five expert interventional radiologists trained in the technique developed by Carnevale et al. [12]. Unilateral femoral access under local anesthesia was used to perform embolization from two positions in the inferior vesical artery (IVA): an initial proximal position just beyond any collateral branches to adjacent structures, and then from distal positions within the intraprostatic branches of the IVA. Pelvic arterial anatomy was bilaterally assessed and classified according to de Assis et al. [13]. Progreat 2.0 microcatheters (Terumo, Tokyo, Japan) and Phantom 0.016 (Boston Scientific, Boston, MA, USA) or BMW Hi-Torque Balance Middleweight Elite 0.014 (Abbott Vascular, Abbott Park, IL, USA) guidewires were used to superselectively catheterize arterial branches to be embolized, and 300–500 μm Embosphere Microspheres® (Merit Medical Systems, South Jordan, UT, USA) were employed to occlude the prostatic arteries. Procedural technical success was defined as bilateral embolization.

Statistical analysis

Data were stored anonymously using Microsoft Excel (Microsoft Corporation, Washington, USA). Descriptive analysis was performed blindly by another author using SPSS version 20 (IBM Corporation, Armonk, NY, USA). Each conflict was solved by senior authors (E.M., A.R., and M.S.). We estimated median and interquartile range (IQR) for each quantitative variable, while we reported the occurrence of the various outcomes for qualitative variables.

Results

We included 10 patients with SCI requiring PAE due to BPH-related difficulties during IC (Table 1). The neurological level of SCI was the following: C1-4 AIS A-C (n = 2), C5-8 AIS A-C (n = 3), T1-S5 AIS A-C (n = 4), and AIS D (n = 1). The SCI etiology was traumatic (n = 8, 80%), vascular (n = 1, 10%), and degenerative (n = 1, 10%). The median age was 70 years (IQR: 64-76, range: 59-86). The median time lapse from SCI to PAE was 5 months (IQR: 3-10, range: 3-224). Five (50%) patients were under antiplatelet therapy, which was not interrupted for the procedure.

Table 1 Pre-, intra- and post-procedural data of the considered population (n = 10). The pre- and post-procedural evaluation of the prostate volume was performed by magnetic resonance imaging. Post-procedural complications were recorded within a median follow-up of 33 months (range: 6-59).
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Seven out of 10 (70%) patients had IDC, while the others (n = 3, 30%) performed IC with Tiemann tip catheters, experiencing several difficulties (i.e., macrohematuria, recurrent UTIs, partial mechanical obstruction). The pre-procedural PV ranged from 40 to 114 ml (median: 61, IQR: 44-86).

The median procedure time was 130 min (IQR: 118–143, range: 105–155). No intra-procedural complications occurred. Technical success was achieved in 9/10 (90%) patients. Case n°3 underwent unilateral PAE due to stenosis of the prostatic vasculature on the left pelvic side (Fig. 2). After recovering without any adverse events, he was able to perform IC without any complications.

Fig. 2: Intra-procedural images of Case n°3, who was the only patient in our series (n = 10) to undergo a unilateral prostatic artery embolization.
figure 2

A Initial angiogram of the right side showed patent vessels to embolize. B Angiogram of the left side showed a stenosis (arrow) which prevented prostatic artery embolization on this side.

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The classification of prostatic artery anatomy was the following: for the right side type I (n = 4), type II (n = 3), type III (n = 1), and type V (n = 1); for the left side type I (n = 4), type II (n = 3), type III (n = 1), and type IV (n = 1).

After 15–30 days, 7/7 (100%) patients removed IDC and started IC safely.

After 6 months, we registered a median post-procedural PV of 50 ml (IQR: 34–77; range: 32-89 ml). The percentage reduction ranged from 10.2 to 28.3% (median: 19.6%, IQR: 12.2–22.9).

We observed no post-procedural complications and all patients continued with IC within a median follow-up of 33 months (IQR: 31–55, range: 6–59). The bladder management after PAE was based on IC (10/10, 100%), MRA (7/10, 70%), and periodical injection of botulinum toxin into the external urethral sphincter (1/10, 10%). Among people performing IC, the Tiemann tip was adopted in three cases who previously had IDC.

Discussion

The epidemiology of SCI has changed over the past several decades: survival rates after trauma and life expectancy significantly have increased thanks to improved clinical management and advanced therapies [14]. This trend led to an increased number of older patients with functional deficits secondary to SCI and a corresponding shift in the comorbidities that contributed to patient management considerations [15]. Among them, BPH represents one of the most common benign conditions, affecting 70% of men in their 60s and 80% of those aged 70s or older [16]. Considering the frequency of SCI is higher in males, the rising prevalence of SCI in older patients indicates that concurrent BPH may present an increasing challenge to bladder management in this population [17]. In people without sensory impairment, BPH typically presents as a constellation of irritative and obstructive lower urinary tract symptoms (LUTS) that can be managed medically or surgically [18, 19]. Sensory deficits may prevent people with SCI from experiencing BPH-related LUTS. In this population, BPH usually manifests as difficulties with IC (e.g., macrohematuria, urethral trauma, UTI), requiring IDC, which is associated with significant issues [5]. Therefore, BPH-related symptom questionnaires, which are usually adopted in general population, are not applicable to evaluate the PAE efficacy in people with SCI.

Since the first description in 2000, PAE has gained popularity as a minimally invasive therapy for BPH that relieves symptoms and achieves functional improvements by inducing an infarct of the prostatic parenchyma, thus reducing PV [20, 21]. PAE is a particularly appealing therapeutic option for poor surgical candidates who have failed medical management, as it is usually performed under local anesthesia and without interruption of anticoagulation regimens or concomitant therapies to manage comorbidities; indeed, the procedure has been successfully performed in patients with prostate sizes exceeding 500 g, in people receiving chemotherapy to treat concurrent cancer diagnoses, and those requiring IDC for extended periods [13, 22,23,24]. The safety profile of the procedure is characterized by mild, transient pain and bleeding events, but significant ischemic and radiation-related complications are possible [25,26,27]. These complications may be masked by the absence of pain in people with SCI. Indeed, they must be monitored carefully during and after the procedure, as the surgical stress may even trigger life-threatening dysautonomic crises, characterized by severe hypertension, tachycardia, vomiting, excessive sweating, and salivation [28]. As for blood pressure, we monitored it constantly, and it remained within normal range values throughout all the procedures. In our limited case series, we did not experience any intra- and post-procedural complications. However, the authors advocate PAE in centers with expert interventional radiologists and doctors specialized in the management of SCI to limit the risk of complications and manage appropriately the issues related to SCI [29].

The results of the current case series are in line with the PAE-related published literature: in particular, our median PV reduction of 19.6% after 6 months was comparable with the previous investigations reporting mid-term PV reductions ranging from 19.2 to 32.8% after 3-6 months since PAE, with a trend towards improved volume reduction and symptom relief following bilateral rather than unilateral embolization [13, 20, 22, 30, 31].

A meta-analysis comparing PAE versus trans-urethral resection of the prostate, considered as the gold-standard treatment for BPH, proved PAE was associated with significant advantages regarding safety and sexual function, but clear disadvantages regarding patient-reported and functional outcomes (e.g., maximum urinary flow, post void residual, and prostate volume reduction) [32]. Since the considered population does not report specific problems related to symptoms and undergoes PAE not to improve micturition, but to perform IC safely and easily, clinicians should offer effective treatment options associated with a reduced morbidity, like PAE [33].

PAE is thought to address both the static and dynamic components of BPH by debulking the enlarged gland and reducing intraprostatic innervation. According to authors, the valid PV reduction observed in spinal cord injured people could be due to the synergistic effects of prostate ischemia due to PAE and the absence of trophic stimuli due to SCI [34,35,36].

As for the evaluation of the procedural success, the authors believe the reduction of prostate specific antigen (PSA) is not a good indicator in people having IDC or undergoing IC, as the PSA may be altered due to prostate inflammation related to catheter irritation.

Our study presented some limitations. The considered sample was small, even if it was representative of the cohort followed by a tertiary referral center for SCI with the same strategy for the management of all sacral area dysfunctions (i.e., bladder, bowel, and sexuality). Another limit is represented by PV evaluation only after 6 months since PAE.

Further studies with larger samples and longer follow-up should assess the persistence of PV reduction over the years and the adverse event profile of PAE in this population, which may differ from that reported in able-bodied individuals for the reasons discussed above.

Conclusions

The current case series outlined the feasibility, safety and efficacy of PAE in people with SCI suffering from concomitant BPH, which represents a raising problem among old males. The minimal comorbidity may make PAE the gold standard for BPH treatment in this frail population, even if further studies are mandatory to test definitively our conclusions before warranting PAE widespread adoption in individuals with SCI.

Data archiving

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.