Abstract
Introduction:
Neurological disease is a known entity for causing erectile dysfunction (ED). Pharmacological therapies are not always effective these patients – penile prosthesis implant (PPI) is an established surgical treatment option. For a variety of reasons, neurological patients may experience differing outcomes of PPI compared to those whose ED arises from other causes. We investigated outcomes of PPI in neurological patients using the Italian multi-institutional national registry of penile prostheses [Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED)].
Methods:
Patients undergoing PPI were investigated via the INSIST-ED registry, from 2014 to 2021. Data were prospectively recorded by 45 surgeons on a dedicated website (www.registro.andrologiaitaliana.it) and reviewed by a data manager. We subselected patients with neurological disease undergoing PPI for ED, and these patients were reviewed at 3, 6, and 12 months, and annually thereafter. Postoperative complications and functional outcomes were evaluated through validated questionnaires [International Index of Erectile Function-5 (IIEF-5), Sexual Encounter Profile 2–3, and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS)]. A nonvalidated questionnaire was administered to assess patient satisfaction.
Results:
A total of 33 patients were included with a median age of 49 [interquartile range (IQR) 41–55]. Median follow-up was 83 months (IQR 67–99.5). A penoscrotal approach for PPI was performed in most cases (90.9%), while infrapubic was used in three cases (9.1%). Inflatable and malleable devices were implanted in 30 (90.9%) and 3 cases (9.1%), respectively. Intraoperative complications occurred in one case (3%). Early postoperative complications (<90 days) were observed in three cases (9.1%): two wound dehiscence (Clavien-Dindo G1 and G3a respectively) and one device infection requiring prosthesis explant (Clavien-Dindo G3a). Mechanical failures of inflatable devices were not observed during the follow-up period. Median IIEF-5 before surgery was 8 (IQR 7–9). At the latest follow-up, IIEF-5 was 22 (IQR 19–23.5), and median EDITS was 79 (IQR 64–88). A total of 28 patients (84.8%) self-reported to be fully satisfied with the PPI.
Conclusion:
Although PPI in the neurological population has been historically considered to be at increased risk, in our study, PPI complications and infections rates in this cohort did not differ from general population.
Introduction
Neurological diseases such as spinal cord injury (SCI), multiple sclerosis, spina bifida, and Parkinson’s disease include sexual dysfunctions, most notably erectile dysfunction (ED), within their spectrum of symptoms. ED may result in significant impairment of quality of life; hence, it requires considered attention by clinicians. 1
According to the European Association of Urology guidelines, ED should be addressed pharmacologically at first. Phosphodiesterase-5 inhibitors are considered the first-line treatment for ED proving to be effective and safe. Intracavernosal injection of vasodilators, such as prostaglandin E1, can be considered as a valuable alternative. 2
Despite the range of oral or intracavernosal medications, or alternative treatments such as vacuum devices available for the treatment of neurogenic ED, a proportion of patients will achieve suboptimal responses. Such patients may require a penile prosthesis implant (PPI). 2 Historically, PPI in neurological patients was considered with additional caution, because of a suspected higher incidence of postoperative complications when compared to general population.3,4 The complication more frequently reported was prosthesis infection. Despite the complication risk, however, several studies3,5–9 highlight high satisfaction rates in this population. Current literature unfortunately is limited, noncontemporary, and lacks high-powered studies supporting the role PPI to treat end-stage neurogenic ED.3,6,8–10 This paper presents the outcomes of a multicentric cohort of patients affected by neurological conditions, whom underwent PPI for the treatment of neurogenic ED.
Material and methods
The Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED) Registry is an Italian prospective database of PPI surgeries. 11 The registry includes demographics, surgical procedures, devices, surgical and functional outcomes, and duration of follow-up. All data are prospectively recorded by implanting surgeons on a dedicated website (www.registro.andrologiaitaliana.it) and revised by a data manager. A demonstration version of the INSIST-ED registry is accessible at http://registro.andrologiaitaliana.it/ (username: demo@registrosia.it; password: RegSia2015_demo). In the present study, data from the INSIST-ED registry relate to patients whom underwent PPI from 2014 to 2021. Patients with neurological conditions suffering from medically refractory ED, who underwent either inflatable or malleable PPI, were included in the analysis. Patients with iatrogenic neurogenic ED (pelvic surgery or external beam radiotherapy) and patients with incomplete follow-up data were excluded. Preoperative evaluation included a detailed medical and sexual history, bladder voiding management, medication use, duration, and progression of symptoms.
The parameters considered for surgical outcomes analysis included operative time, prosthesis model and length, use of rear-tip extenders, reservoir placement site, intraoperative adjuvant maneuvers to address penile curvature, as well as intraoperative and postoperative complications (utilizing the Clavien-Dindo scale 12 ).
Functional outcomes were assessed with both validated and nonvalidated questionnaires. Preoperatively, patients completed the International Index of Erectile Function-5 (IIEF-5) questionnaire 13 and items 2 (‘Were you able to insert your penis into your partner’s vagina?’) and 3 (‘Did your erection last long enough for you to have successful intercourse?’) of the Sexual Encounter Profile (SEP) questionnaire. 14 At 6 and 12 months following the procedure, patients were invited to complete the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), 15 and the IIEF-5 and SEP (items 2–3) questionnaires. Patient overall satisfaction and penile length satisfaction were evaluated, respectively, with ad hoc questionnaires based on two questions, ‘Are you satisfied about the effects of PPI on your sexual life?’ and ‘Are you satisfied with the length of the erect penis after the surgical procedure?’, rated on a five-point Likert scale (Figure 1).
Likert’s five-point scale on ‘ad hoc’ questions about patients’ satisfaction toward the PPI.
Privacy protection
The INSIST-ED registry protects patient privacy; no sensible data (i.e., patient name, date of birth, address, etc.) are present in the registry. For the protection of the privacy of each implanting surgeon, individual surgical data inserted in the registry can be accessed solely by the National Registry Coordinator and the Registry Monitor; Registry data are elaborated and circulated in a aggregated fashion only: no implanting surgeon can access data produced by individual implanting surgeons. Similarly, it has been the choice of the Registry Board, on behalf of Società Italiana di Andrologia (S.I.A.), to report device data in an aggregated fashion only: three-component hydraulic devices, two-component hydraulic devices, and malleable devices. The ‘Registry Project’ has been evaluated, before approval, by S.I.A, legal office, in particular under the profile of the patient privacy and anonymity protection law, and it has been found sound in this perspective.
Statistical analysis
Descriptive and inferential data analysis was performed using IBM SPSS Statistics for Windows, version 28 (IBM Corp., Armonk, NY, USA). Normal distribution of variables was tested by the Kolmogorov–Smirnov test. The categorical variables were described using frequency and percentage. Differences between groups were tested by the chi-squared test, Fisher’s exact test, Student’s independent t test, or the Mann–Whitney U test. Continuous variables are presented as median and interquartile range (IQR) or mean and standard deviation. Univariate logistic regression analysis was performed to investigate the association between neurological disease and complications. Variables with p value < 0.05 in the univariate analysis were then included in the multivariate stepwise logistic regression model. Two-sided p < 0.05 was considered to be statistically significant.
Results
A total of 33 patients met the inclusion criteria and were enrolled in the current study. Median age was 49 years (IQR 41–55) and median follow-up was 83 months (IQR 67–99.5). Table 1 summarizes patient clinical features. A total of 23 patients (69.7%) suffered from SCI, 4 (12.1%) were diagnosed with multiple sclerosis, while 3 (9.1%) were affected by parkinsonism. The remainder (9.1%) suffered from rare neurological conditions: Arnold Chiari Syndrome, Charcot-Marie-Tooth disease, and mitochondriopathy. Tables 2 and 3 illustrate the detail of implanted penile prosthetic devices and distribution for neurological disease category. An inflatable device was implanted in 30 (90.9%) cases, including the AMS 700 (American Medical Systems – Boston Scientific, Maple Grove, MN, USA), Coloplast Titan (Coloplast Inc., Minneapolis, MN, USA), and Zephyr ZSI 475 (ZEPHYR Surgical Implants Sarl, Geneva, Switzerland), respectively, in 22 (66.7%), 6 (18.2%), and 2 (6.1%) patients. In the remaining cases (9.1%), a malleable prosthesis was used: 2 (66.7%) AMS Spectra (American Medical Systems – Boston Scientific, Maple Grove, MN, USA) and 1 (33.3%) Coloplast Genesis (Coloplast Inc., Minneapolis, MN, USA). Intraoperative and postoperative features are listed in Table 4. A total of 30 (90.9%) of PPI were conducted through a penoscrotal approach, while an infrapubic approach was reported in 3 (9.1%). For the three-piece PPI, reservoirs were placed in the retropubic space of Retzius in 20 (60.6%) cases, in a submuscular ectopic space in 1 (3.3%) of cases, and an extraperitoneal space through a second abdominal incision in 9 (27%) of patients. The length of cylinders inserted ranged from 14.5 to 24 cm, with a median length of 19 cm (IQR 17.5–20). Median operative time was 100 min (IQR 72.5–120). In two patients (6.1%), a modeling maneuver 16 was employed for the management of a residual post PPI penile curvature.
Descriptive characteristics of patients suffering from neurogenic ED who underwent PPI.
A, American Spinal Injury Association, no sensory or motor function reserved in the sacral segment; B–D, partial sensory or motor function preserved; CIC, clean intermittent catheterization; ED, erectile dysfunction; IQR, interquartile range; MS, multiple sclerosis; PPI, penile prosthesis implantation; SCI, spinal cord injury; SE, spontaneous evacuation; SV, spontaneous voiding.
Penile prostheses devices characteristics.
Penile prostheses devices distribution for neurological disease category.
MS, multiple sclerosis; SCI, spinal cord injury.
Surgical procedure features of PPI.
IQR, interquartile range; PPI, penile prosthesis implant.
Intraoperative complications were uncommon (3%). These included a single case of distal cylinder crossover, which was immediately recognized and corrected. Postoperative complications occurred in a total of three patients (9.1%) including one (3%) acute device infection requiring surgical explantation (grade 3a), as well as two patients (6.1%) who experienced a wound dehiscence which were managed conservatively in one patient (grade 1), while the second patient required surgical wound revision (grade 3a).
Table 5 summarizes functional outcomes. A statistically significant improvement of IIEF-5 was observed between the preoperative and 12 months postoperatively (p < 0.001). The positive responsive rates to SEP-2 and SEP-3 showed significant improvements at 12 months compared to baseline. Median EDITS value at 6 and 12 months were, respectively, 78 (IQR 66–87) and 79 (IQR 64–88). Patients reported to be very satisfied (84.6%) or satisfied (6.1%) with the procedure. Overall satisfaction with the procedure was reported by 90.7% of the patients. The patient (3%) whom had their device explanted for infection reasons was completely unsatisfied. Satisfaction with penile length was observed in 27 (81.8%) patients, 13 of them (39.4%) declared themselves very satisfied, and 14 (42.4%) were satisfied.
Functional outcomes after PPI.
EDITS, erectile dysfunction inventory of treatment satisfaction; IIEF, international index of erectile function; IQR, interquartile range; mo, Month; PPI, penile prosthesis implant; SEP, sexual encounter profile.
Discussion
This study presents the outcomes of a relatively large cohort of patients with neurological conditions, who underwent PPI with a median follow up of 83 months. We observed an overall complication rate of 9.1%, which decreased to 6.1% when considering only high-grade complications (Clavien ⩾ 3). A total of 90.7% of patients were satisfied, which correlates with previously reported literature.5,17 Our study showed that early high-grade complications requiring the prosthetic explantation were no higher than in the general population, and the subjective satisfaction was as high as in the general population. Indeed, a systematic review which indagated the outcomes of penile prosthesis in general population published in 2020 by Mahon et al. reports an infection rate of 5% or less. 18 Similarly, the satisfaction rate in general population is above 90%. 19
Neuro-urological patients are inherently considered at higher risk of complication following PPI due to the need for clean intermittent catheterization (CIC) or indwelling urethral catheter much more frequently that the general population. Urethral catheterization was associated with a risk of infection and erosion up to 50%. 20 The explanation could reside in impaired sensibility that could lead not to notice possible traumatisms during CIC and the frequent bacterial colonization of the urinary tract in case of urethral catheterization. In our series, 1 out of 10 patients (10%) requiring CIC underwent penile prosthesis explantation for device infection. Even so, PPI can be a valuable tool in aiding the very bladder emptying since it can facilitate the CIC maneuver or the use of urinal condom in patients with limited manual ability or hidden penis. 9 Moreover, the risk of infection and erosion could arise in the presence of pressure sores, which are most frequent in neuro-urological patients. 21
Within current literature, there are several reports describing high complication rates in PPI in patients affected by neurogenic ED. In a study published in 1988, 3 17 out of 63 (33%) patients implanted with either a malleable or an inflatable penile prosthesis, required early explant due to complications. In 1994, 10 a prosthesis removal rate of 13.3% was reported, including nine due to extrusion or infection and three due to difficulty in bladder catheterization. Patient reported satisfaction remained high, with 63/69 patients declaring themselves satisfied by the procedure in the second study. Of note, the vast majority of patients (84% in the first and 100% patients in the second study) underwent malleable prosthesis implantation, which may have impacted both complication and satisfaction rates. A recent systematic review investigated the outcomes of PPI in SCI patients. 17 Overall complication rates of 4.2–61.1% were reported. Infection occurred in 0–16% cases, erosion in 3.7–11.1% and mechanical failure in 0–16.7%, which is generally higher that the data reported for general population 18 despite the great heterogeneity of data. The explantation rate was 2.1–16.7% and the revision rate was 2.7–44.4%. Again despite these revision rates, 79.2–92.9% of men were satisfied by the procedure. The review concludes that malleable prostheses are at increased risk for erosion (20.8%), while inflatable prostheses pose a higher risk for infection and mechanical failure (20% and 20% respectively). According to the review, complications are more likely in SCI population than in general population.
The most evident aspect of the data reported is the great heterogeneity among studies, with some series reporting complication rates as low as 4.1%. 22 While there are some contemporary data on this subject, the majority of studies were published prior to the year 2000. Even in those published after 2000, they often report series of patients implanted before the turn of the century. Several advances had taken place since then which may affect current data. These include antibiotic-coated and hydrophilic coated prostheses which were introduced in 2001–2002, reducing infectious complications by up to 50%. 23 The evolution of techniques has led to a reduction of complications, such as the ‘no touch’ technique introduced by Eid et al. 24 Thus, the presence of a vast majority of older studies in literature may be considered as a major bias in the evaluation of complications. We believe that those technological innovations can largely influence the outcomes of PPI even in neuro-urological patients. Moreover, another aspect that should be taken in account is the progressive improvement in bladder management in neuro-urological patients and the evolution in technology and materials also in CIC, which could result in less traumatic catheterization and less infections. 25
In order to further limit complications, as per the general population, PPI should be carried out by experts in high-volume centers. 2 It is the author’s opinion that in order to minimize complications, PPI in patients affected by neurological conditions should be performed in centers very acquainted with both patients affected by neurological conditions and penile prosthetic surgery.
Considering the abovementioned aspects and considering the high patient’s reported satisfactions (which is a well-documented aspect in literature), PPI in patients affected by neurological conditions nowadays should be reexamined in the light of new technologies and new techniques and should be carried out by referral centers for both neuro-urology and ED treatment. These observations are partly confirmed by a recent study by Xardel et al., 5 which included 27 patients implanted with inflatable penile prostheses with a mean follow-up (FU) of 6 years. In this study, even if a high overall complication rate of 29.6% was reported, only two cases were due to infection. Similarly, our series of patients, which started from 2014, acceptable rates of complications when all the abovementioned criteria are satisfied.
While the data from our study are pleasing, it is not devoid of limitations. Our data have been collected in high-volume centers and, thus, may not be applicable to all clinical contexts. The reliability of the data is dependent on the surgeons collecting it, with a possibility of excluding certain revision surgeries or complications particularly if patients had any subsequent surgeries outside of Italy. It is important to notice that our study involved any patients with a neurological condition, with various grade of severity. This was due to a lack of numerosity that could not allow us to perform a significant subanalysis of PPI outcomes based on the type and degree of severity of the pathology. It is indeed possible that our results are influenced by the relatively low number of patients performing CIC and the relatively low number of patients affected by ‘severe’ neurological conditions such as tetraplegic ASIA-A patients.
Conclusion
High-quality prospective studies are warranted in order to further assess the safety and efficacy of PPI in patients with neurological conditions; nevertheless, the indication of PPI implantation in neuro-urological patients should not be excluded a priori due to concern for complications.
Footnotes
Acknowledgements
The authors have no financial disclosures. No funding was provided for this study. The authors want to thanks the INSIST-ED registry group for the realization of this paper (Pescatori E.; Caraceni E.; Colombo F.; Vitarelli A.; Paradiso M.; Cai T.; Carrino M.; Franco G.; Schifano N.; Fiordelise S.; Silvani M.; Mondaini N.; Varvello F.; Palumbo F.; Avolio A.; Antonini G.; Corvasce A.; Pozza D.; Bitelli M.; Boezio F.; Conti E.; Negro C; Vicini P.; Ghidini N.; Alei G.; Italiano E.; Polito M.; Natali A.; Tamai A.).
