Penile Glans Necrosis Following Prostatic Artery Embolization for Benign Prostatic Hyperplasia: Case Series and Review of Current Literature

Abstract

Purpose

To report a case series of 6 patients with penile glans necrosis (PGN) following prostatic artery embolization (PAE) and review the current literature relating to PAE and PGN, including the emerging role of hyperbaric oxygen therapy (HBOT) for PGN.

Materials and Methods

All patients have failed medical BPH therapy and chose to undergo PAE over other minimally invasive BPH surgery. Patient demographics, preoperative and postoperative validated questionnaires such as the International Prostate Symptom Severity (IPSS) and International Index of Erectile Function (IIEF) scores, treatment-related adverse events (TRAE) and subsequent treatment for PGN were reviewed. All patients were follow-up with a minimum of 12 months post-PAE.

Results

Between January 2018 and June 2020, six males with a mean age of 52.3 years (44–66 y) received PAE for BPH therapy. An immediate postoperative PGN was recognised in 4 out of 6 patients with the mean penile glans pain score of 3 and 4 patients reported altered penile glans sensitivity. Comparing the mean (and median) IPSS and IIEF-5 scores were 16.5 (16) and 21.3 (21) pre-PAE, there was improvements in IPSS and IIEF-5 scores at 12.0 (12) and 18.0 (18) at 12 months review. All patients reported normal penile glans sensitivity and only 1 patient reported an on-going penile glans pain (score 2). Four patients received HBOT while 2 patients elected for conservative care. All patients reported worse erectile function scores despite complete resolution of PGN.

Conclusions

PGN is a rare but serious complication of PAE with ensuing erectile dysfunction. HBOT appears to expedite the recovery process in men with PGN related to PAE with better erection scores compared to conservative measure.

INTRODUCTION

Benign prostatic hyperplasia (BPH) and ensuing lower urinary tract symptoms (LUTS) can adversely impact across various quality-of-life domains [1]. While transurethral resection of the prostate (TURP) is often considered the standard surgical treatment for men with medical refractory BPH/LUTS [2], many younger males are keen to avoid TURP due to sexual complications such as erectile dysfunction (ED) and retrograde ejaculation or anejaculation [3]. In recent years, there is increasing interest and greater demands for minimally invasive surgical therapy (MIST) for BPH/LUTS given the emphasis on the preservation of erectile and ejaculatory functions.

Prostatic artery embolization (PAE) is a minimally invasive radiological intervention designed to induce ischaemia and subsequent shrinkage of the enlarged prostate through the injection of particulate microembolic agents directly into the prostatic artery [2]. Published literature including systematic reviews and meta-analyses have shown that PAE can be effective and safe in a carefully selected group of men with BPH/LUTS [2,4,5]. Nonetheless, PAE requires considerable radiological expertise since non-target embolization even in the setting of super-selective angioembolization can occur, resulting in ischemia and ulceration of embolized pelvic organs.

While most of these non-target organs ischemia is often self-limited, some can have serious complications with long term impact in male sexual function domains [5]. Herein, we report a case series of 6 patients who presented with penile glans necrosis (PGN) following PAE. This paper examines the current literature relating to PGN and PAE, and the evidence for hyperbaric oxygen therapy (HBOT) for PGN.

MATERIALS AND METHODS

Following Institutional Ethics Review Board approval, all PGN cases related to PAE between January 2018 and June 2020 were reviewed in a prospectively collected database in a tertiary specialist centre. Patients chose PAE over other BPH surgical modalities under the understanding that PAE is considered minimally invasive with minimal adverse sexual events. Since this database does not include all patients that had PAE, rather males presenting with sexual dysfunction, data regarding the total number of PAE performed or actual incidence of PAE-related PGN was not available. PAE procedure was conducted after preprocedural imaging with computed tomography angiogram (CTA) to define the tributaries of the internal iliac arteries and both prostatic arteries were embolized using trisacryl microspheres (Embosphere^® Microspheres; Merit Medical, South Jordan, UT, USA). Patient demographics, clinical presentation, PAE findings including treatment-related adverse events (TRAE) and subsequent treatments for PGN were reviewed and discussed. Medical records pertaining to each patient’s care was requested by the individual patient and author as the treating clinician, and all available data were recorded in the database. All patients received a minimum of 12 months follow-up post-PAE. Comparison between preoperative and postoperative validated questionnaires such as the International Prostate Symptom Severity (IPSS) and International Index of Erectile Function (IIEF) scores as well as uroflow rate (Qmax) were recorded too. Penile glans pain score was rated on a visual analogue scale from 0 to 5 (0 means no pain and 5 means the worst possible pain).

Ethics statement

The present study protocol was reviewed and approved by the Institutional Review Board of the Princess Alexandra Hospital, University of Queensland (Approval No: HREC/18/QPAH/178). Informed consent was signed by all subjects.

RESULTS

Over the two and half years, a total of six males with a mean age of 52.3 years (44–66 y) presented with PGN following PAE treatment for medical-refractory BPH symptoms (Table 1). All patients have been on BPH medications for more than 6 months with minimal benefits. Two of the patients reported a history of hypertension and hyperlipidemia, and none of the males has a history of renal failure, diabetes, or cardiac disease. All males were sexually active and can achieve a spontaneous erection for sexual intercourse. The mean (and median) IPSS and IIEF-5 scores were 16.5 (16) and 21.3 (21) while the uroflow rate was 7.7 mL/s (7.6 mL/s) (Table 1). The mean (and median) prostate size on CTA was 78.6 g (80 g).

Table 1. Selected variables on patient demographics pre- and post-PAE at 6 and 12-months.

Variable	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6
Age (y)	44	52	66	48	49	55
Duration of BPH (y)	2	4	5	3	4	3
Preoperative IPSS score	18	16	14	16	17	18
Preoperative IIEF-5 score	21	22	21	22	21	21
Preoperative Qmax (mL/s)	8.2	7.6	6.9	8.1	7.6	8.0
Prostate volume on CTA (cm3)	75	80	100	82	80	68
Duration of PAE procedure (min)	60	45	65	55	65	55
Postoperative IPSS score at 6 months	16	14	10	14	14	12
Postoperative IIEF-5 score at 6 months	19	18	18	19	18	19
Postoperative Qmax (mL/s) at 6 months	14.5	12.3	8.8	11.8	13.5	13.8
Postoperative IPSS score at 12 months	14	12	10	12	14	10
Postoperative IIEF-5 score at 12 months	19	18	18	18	17	18
Postoperative Qmax (mL/s) at 12 months	14	12	8	10	12	12
Treatment received for PGN	HBOT	Conservative	HBOT	HBOT	Conservative	HBOT
Time to resolution of glans penis colour (mo)	3	6	3	4	6	4

PAE: prostatic artery embolization, BPH: benign prostatic hyperplasia, IPSS: International Prostate Symptom Severity, IIEF: International Index of Erectile Function, CTA: computed tomography angiogram, PGN: penile glans necrosis, HBOT: hyperbaric oxygen therapy.

Bilateral super-selective PAE was conducted through either unilateral brachial artery (4 patients) or femoral artery (2 patients) punctures and complete bilateral prostatic arteries embolization were undertaken. The mean (and median) duration of PAE was 57.5 minutes (55 min). Additional cone-beam CTA was performed to confirm catheter position and prostate staining if there was suspicion of potential non-prostate embolization.

Immediate penile glans discolouration and pain was recognised in 4 out of 6 patients, and intraoperative CTA identified occlusion of collateral vessels from the lateral prostatic artery to the penis. Other TRAE included mild hematuria (all patients) and hematospermia (4 patients). The mean (median) penile glans pain score was 3.0 (3) and 4 patients reported altered penile glans sensitivity. All patients were referred and seen in the same week for urgent urological opinion. Clinical examination showed the presence of a necrotic ulcer surrounded by a zone of erythema and purplish discolouration on the glans penis which is indicative of PGN (Fig. 1). A formal cystoscopy examination was not conducted since every patient was able to void and there was no passage of blood clot or urinary retention. Following discussion regarding potential treatment strategies for PGN, 4 (67%) patients underwent HBOT to treat worsening PGN at 2 weeks post-PAE, while 2 (33%) patients elected for conservative watchful observation due to lack of time to attend HBOT (1 patient) and distance of travel for HBOT (1 patient).

Fig. 1. Penile glans necrosis following prostatic artery embolization (in patient 1). The evolving appearance penile glans necrosis in patient 1 from (A) ischemic penile glans at day 1, (B) established glans ulceration at week 4, and (C) resolving penile glans necrosis at 6 months review.

While the complete resolution of the PGN was achieved by all patients at the 6-month review and there were some improvements in the urinary function based on the changes in IPSS, all males reported a slight reduction in sexual function with lower IIEF-5 scores. At the 12 months follow-up, all patients who achieved complete resolution of the PGN did not experience any relapse of signs and no patient had evidence of meatal stenosis. All patients reported normal penile glans sensitivity and only 1 patient reported an ongoing penile glans pain (score 2). The mean (and median) IPSS and IIEF-5 scores were 12.0 (12) and 18.0 (18) at 12 months post-PAE (Table 1) and the recovery was faster with higher mean IIEF-5 scores following HBOT as compared to conservative measure (18.3 vs. 17.5) although this was not statistically significant (p>0.05).

DISCUSSION

PAE has gained considerable popularity as a MIST to treat BPH/LUTS especially among the interventional radiology community in the last decade [6]. In recent years, there have been further refinements in the technical aspects of PAE including the selection of the ideal patient and embolization techniques, as well as an optimization on the types and sizes of embolic agents to improve the clinical efficacy and safety outcomes [7]. According to the recently published American Urological Association (AUA) guideline on the management of LUTS/BPH [8], the current data does not support PAE as a routine treatment of LUTS/BPH, with treatment benefit over risk remains unclear, such that PAE should not be recommended for standard treatment outside the context of clinical trials (expert opinion). Similarly, the European Association of Urology (EAU) [9] advocates a need to better define the selection criteria of patients who will benefit from PAE and that PAE impacts the entire prostate without the option for focused and controlled action on bladder outlet obstruction. The National Institute for Health and Care Excellence (NICE) has issued a supporting statement that PAE can be accepted as a standard procedure in the management of symptomatic BPH under the guidance of a urologist and an interventional radiologist, provided that standard arrangements are in place for clinical governance, consent and audit [10]. In contrast, the Society of Interventional Radiology has released a position statement to support PAE as a novel and promising BPH therapy with reasonable safety and efficacy as well as high patient satisfaction rates [11].

The fundamental success of PAE is highly dependent on the operator [12], embolization technique(s) [13] and variations in the anatomy of the prostatic artery [14]. The prostatic artery is often tortuous especially in larger prostate and can be asymmetric between the pelvic sides, with variable origin of the prostatic artery, vessel size and extra-prostatic anastomoses [14,15]. While the ideal embolization particle size is yet to be determined, studies have reported equivocal outcomes between smaller and larger sized microspheres [15]. Although smaller sized microspheres may be more effective in reaching the terminal branches of the prostate artery, they could be riskier due to inadvertent embolization of non-target pelvic organs [15]. From a technical aspect, cone-beam CT performed at the time of PAE can assist with the identification of prostatic artery anastomoses resulting in safer and more effective embolization compared to conventional angiography [16]. Advanced embolization techniques such as the PERFECTED (Proximal Embolization First, Then Embolize Distal) technique has been developed to increase the embolic load administered to the prostate and avoid early proximal occlusion [17]. While this proposed technique lowers the risk of reflux during embolization and is associated with lower rates of symptom recurrence and ischemic complications [18], there are some risks with over-embolization due to smaller particles emboli (<300 µm) [19].

Reported PAE-related TRAE includes post-PAE syndrome, dysuria, urinary tract infection, hematuria, hematospermia and urinary retention [20,21] while serious complications due to non-target embolization can result in ischemia and/or ulceration of bladder, rectum, or penis [22,23,24,25,26]. PGN can occur following inadvertent embolization and subsequent occlusion of branches of common penile artery and bulbourethral artery resulting in congestive hyperaemia, necrosis, and ulceration of the glans penis. In our study, all patients reported hematuria and two-thirds of patients had hematospermia. Post-PAE PGN is a rare complication with potential long-term sexual dysfunction and currently, there is minimal published data on this unique clinical entity [23,25,26]. PGN can cause a myriad of sexual dysfunction symptoms such as penile pain, ED, and painful ejaculation. To date, other benign causes of PGN have been reported in the literature and these include infection, foreign body reaction, drugs, and systemic diseases (Table 2) [27,28,29]. While there are no pathognomonic histopathological characteristics to define PGN, the diagnosis often rests on clinical features such as the presence of penile glans discolouration, ulceration, or necrosis. In most benign cases, simple measures such as analgesia and the use of corticosteroid treatment will suffice although healing often takes a considerable amount of time [23,26]. In contrast, malignant causes of ulcerative necrosis of the glans penis require formal glans excision followed by surgical reconstruction of a neoglans for cosmesis and to allow for normal urethral voiding [30].

Table 2. Published data on penile glans necrosis in the literature.

Causation for PGN	Number of patients	Timing	First author surname, reference
BCG/MMC therapy	2	1 month later (BCG)	Kureshi, [27]
		24 hours (MMC)
Silicone injection	1	1 month later	Plaza, [28]
Nicorandil	3	2 years later	Yap, [29]
Post-embolization	1	Recognized immediately	Kisilevzky, [23]
	1	Recognized immediately	Chung, [25]
	1	Recognized immediately	Couture, [26]

PGN: penile glans necrosis, BCG: Bacillus Calmette–Guérin, MMC: mitomycin C.

The early success of HBOT in genitourinary medicine has been observed in the treatment of Fournier’s gangrene, radiation cystitis and calciphylaxis [31]. The HBOT increases the oxygen tension in ischaemic areas by enhancing the amount of dissolved oxygen in the blood and oxygen distribution to affected tissues [32]. It has been reported that HBOT reduces tissue inflammation and encourages antimicrobial action through bactericidal effects of leukocytes and macrophages, enhanced fibroblast growth factor proliferation, promotion of angiogenesis and improved wound healing [30]. Furthermore, HBOT induces the formation of new capillaries to reduce local vasospasm and increases the necessary time for wound healing as well as the induced rate of collagen deposition [32]. In our study, the use of HBOT significantly hasten the recovery of PGN compared to those who elect for conservative care (3 vs. 6 months). Furthermore, the reported IIEF-5 scores were higher in the HBOT groups indicating a potentially greater return of penile sensitivity and higher erectile function, although this did not reach statistical significance.

To our knowledge, this is the largest published case series of PGN following PAE. The use of HBOT expediates the recovery of PGN and appears to be associated with better erectile function compared to those who chose conservative care at 6 months review. Limitations in this case series include potential reporting bias, single-centre data, and a very small patient sample, thereby limiting the generalisability of PGN in PAE. Furthermore, post-PAE PGN is a relatively rare condition compared to other common complications of PAE such as dysuria and hematuria. Nonetheless, the strengths of this paper are a well-documented report of PGN following PAE, prospective outcome data collection, the use of validated outcomes measures and complete follow-up in all patients. As PAE emerges from a novel technique to become a more established minimally invasive BPH treatment option, proper patient counselling and better-informed consent should be obtained due to the potentially rare but serious complications such as PGN related to non-target embolization. Clinicians must understand PAE’s role with its strengths and weaknesses to ensure optimal patient selection since PAE may not be suitable for every patient. Further studies involving multi-centre larger cohort, longer durations of follow-up with well-defined clinical endpoints and imaging parameters are necessary to determine the optimal technique and embolization material(s) for PAE. Direct comparative studies between PAE and other minimally invasive BPH treatments [3], instead of TURP, should be conducted in terms of cost-effectiveness analysis, specific TRAE, ease of therapy administration and impact on various quality-of-life domains scores including sexual profile, should be incorporated into future clinical trials.

CONCLUSIONS

PGN is a rare but serious complication of PAE with ensuing ED and HBOT appears to expedite the recovery process in men with PGN related to PAE with better erection scores compared to conservative measures. It is important to understand that while PAE can have a useful role in LUTS/BPH treatment, this must be done with high technical expertise and strict patient selection coupled with proper informed consent, especially regarding non-target embolization events and longer-term clinical and safety data.