Background: Robot-assisted radical prostatectomy (RARP) is a common curative treatment for localised prostate cancer; however, erectile function is significantly impaired following non-nerve-sparing (NNS) surgery. Contemporary data evaluating erectile dysfunction (ED) treatment outcomes in this cohort remain limited.

Aim: We aimed to evaluate real-world functional outcomes and response to commonly utilised ED treatments following bilateral NNS RARP in contemporary practice.

Methods: We conducted a retrospective single-centre analysis of patients undergoing bilateral NNS RARP with subsequent andrology follow-up over a 6-year period. Patients with any degree of nerve sparing or prior prostate cancer treatment were excluded. Treatment success was defined as patient-reported erections sufficient for penetrative intercourse on at least two occasions. Continence outcomes and subsequent prosthetic surgery were also recorded.

Results: Overall, 402 patients were included, with a mean age of 64.2 years and median follow-up of 23 months. Median baseline and postoperative IIEF-5 scores were 13.5 and 2, respectively. Phosphodiesterase 5 inhibitors were prescribed to 301 patients, with only 5 men (1.6%) achieving erections sufficient for penetrative intercourse. Vacuum erection device was issued to 333 patients, of whom 73 (22%) achieved intercourse utilising the constriction ring. Response rates for intraurethral alprostadil were modest at 14% for Vitaros and 22% for MUSE. Intracavernosal injection with alprostadil and aviptadil phentolamine achieved response rates of 39% and 41%, respectively. Overall, 31 patients (7.7%) underwent or were awaiting penile prosthesis implantation. At ≥12 months, 69% were pad-free and 2.7% required artificial urinary sphincter implantation.

Clinical Implications: ED management following bilateral NNS RARP should be guided by nerve-sparing status, with earlier counselling regarding mechanical, injectable, and prosthetic options that do not rely on intact neurovascular pathways.

Strengths and Limitations: This is the largest contemporary series examining functional outcomes exclusively in patients undergoing bilateral NNS RARP. Limitations include the retrospective design, selection bias from inclusion of patients attending andrology follow-up, and limited use of validated patient reported outcome measures across treatment modalities.

Conclusion: Erectile function after bilateral NNS RARP remains poor, with very limited response to PDE5 inhibitors. However, treatment-assisted penetrative intercourse can be achieved in a subset of patients using vacuum erection devices, intracavernosal injection therapy, or penile prosthesis implantation, supporting earlier treatment escalation and individualised postoperative counselling.

• Erectile dysfunction

• Radical prostatectomy

• Non-Nerve-sparing

• PDE5 inhibitors

• Intracavernosal injection

• Penile prosthesis

di Giovanni A (2026) Erectile Dysfunction Treatment Outcomes Following Bilateral Non-Nerve- Sparing Robot-Assisted Radical Prostatec tomy. JSM Sexual Med 10(3): 1184.

Robotic assisted radical prostatectomy (RARP) has become the main surgical curative option for localised prostate cancer, the most common cancer in men worldwide [1,2].

As patients undergoing RARP achieve excellent long-term oncological outcomes, functional outcomes, particularly sexual function and urinary incontinence,remain critically important determinants of postoperative quality of life [3].

Prior to anatomical radical prostatectomy techniques, surgery often resulted in different degrees of erectile dysfunction (ED) and urinary incontinence [4]. Penile erection requires coordination between varied factors including psychogenic, neurogenic, hormonal and vascular systems. The neural control of erectile function has included two pathways: 1) a sacral parasympathetic centre that can respond to penile or psychic stimulation and 2) a lumbar sympathetic centre that can respond to psychic stimuli. Both nerves pass through the pelvic plexus with branches to the corpora cavernosa that are situated between the rectum and urethra and penetrate the urogenital diaphragm near or in the muscular wall of the urethra [5].

Despite advances in the understanding of pelvic neuroanatomy, postoperative ED rates following RARP remain variable [6]. Resection of the neurovascular bundles during RARP has been consistently associated with reduced postoperative erectile function and a consequent negative impact on patient quality of life [7]. While the widespread adoption of nerve-sparing techniques has improved EF recovery, ED remains common [8]. In contrast, patients undergoing non–nerve-sparing (NNS) RARP are generally considered to have a substantially lower likelihood of preserving EF compared with those receiving nerve sparing prostatectomy [9,10].

Postoperative management of ED following prostatectomy, in the United Kingdom, typically follows a stepwise therapeutic approach, including phosphodiesterase type 5 (PDE5) inhibitors, vacuum erection devices (VED) with application of a constriction ring, and intracavernosal injection therapy (ICI), most commonly using alprostadil (prostaglandin E1) or other combinations such as Bimix, Trimix or aviptadil and phentolamine mesilate (AvP; Invicorp, Evolan Pharma AB, Sweden). However, the response to these interventions in the setting of bilateral complete neurovascular bundle resection remains poorly defined [11,12].

Penile rehabilitation has been proposed as a strategy to promote erectile function recovery following prostatectomy by mitigating corporal hypoxia, smooth muscle apoptosis, and fibrosis during the postoperative period. This approach typically involves the early use of PDE5 inhibitors, VED, ICI, or combination therapies. While animal studies and mechanistic data support the biological rationale for penile rehabilitation, clinical evidence from randomised controlled trials remains inconsistent, with heterogeneous outcomes and conflicting guideline recommendations [13]. Importantly, most available data are derived from cohorts undergoing nerve-sparing procedures, with limited and inconclusive evidence in patients undergoing NNS radical prostatectomy [6,13].

Consequently, the real-world outcomes of established ED treatment modalities in this high-risk subgroup remain poorly defined. The present study therefore aims to evaluate current clinical practice at a tertiary referral centre and to describe the outcomes of commonly utilised ED treatments following NNS RARP, while also characterising continence outcomes in this patient population.

Patient cohort

All operative records for patients undergoing RARP at a single tertiary referral centre were retrospectively retrieved between March 2018 and November 2024. Inclusion criteria comprised patients who underwent elective RARP with bilateral nerve resection (non–nerve sparing) and attended the andrology clinic for follow up on at least two occasions. Patients with any degree of unilateral or bilateral nerve sparing were excluded. Additional exclusions included prior prostate cancer treatments, such as radiotherapy or focal therapy. For patients who developed biochemical recurrence requiring salvage pelvic radiotherapy, outcomes were included up to the commencement of radiotherapy. This study did not require ethics approval and was registered as an audit (registration number 202406).

Standardized protocol

All patients were seen in a specialised ED doctor- or nurse-led andrology clinic following surgery. Penile rehabilitation with the daily use of a VED was offered to all patients routinely with appropriate training. The safe and effective use of a silicone constriction ring was also demonstrated. All ED treatment options were discussed, and initial therapies included PDE5 inhibitors, VED, or alprostadil. Patients were offered on-demand PDE5 inhibitors, including sildenafil 100 mg and/or tadalafil 20 mg, with those failing one agent subsequently offered the alternative. Appropriate instructions regarding timing of tablet administration in relation to sexual stimulation were provided at the time of the initial prescription. A subset of patients were prescribed tadalafil 5 mg once daily on discharge, reflecting a change in institutional protocol over the study period; this was not analysed separately. Patients who did not respond to this approach at their first andrology follow-up were subsequently offered high-dose, on-demand sildenafil or tadalafil.

Additionally, at the initial consultation or following failure of oral medical therapy, patients were offered intraurethral alprostadil preparations in the form of either Vitaros or the Medicated Urethral System for Erections (MUSE), or ICI therapy. The maximum dose of alprostadil ICI used in our institutional protocol was 40 mcg. Patients who experienced inadequate response to alprostadil ICI or developed significant injection-related pain were subsequently offered AvP ICI as an alternative injectable therapy for refractory ED [12].

Patients were taught how to self-administer intraurethral alprostadil or ICI preparation with the first application/ injection performed in clinic. The initial dose was determined by the clinician, considering both the patient’s preference and their response to previous treatment, including erection rigidity and duration. This was followed by a prescription for patients to self administer at home. Follow-up after any tuition consisted of a telephone consultation at 6 weeks as well as a face-to face outpatient clinic appointment at 3 months to ensure correct technique and assess effectiveness. Since 2020, a YouTube video channel has been provided as an additional aid detailing VED use with ring application technique, different alprostadil preparations.

Outcomes measures

Treatment success was defined as the self-reported resumption of penetrative intercourse, sustained on at least two subsequent occasions. This outcome was ascertained through structured patient interview during outpatient consultation. Following initiation of therapy, patients who reported benefit continued to be reviewed at regular intervals to monitor longer-term response and adverse effects. Individuals undergoing ICI titration were specifically flagged during andrology follow-up to ensure that the most up-to-date outcomes were captured for analysis. ICI failure was defined as the inability to achieve erection sufficient for penetration at the maximum dose of the medication at least on 4 occasions. All treatment adverse effects or dropouts were recoded. Follow-up data were collected until January 2026. Continence outcomes were reported at ≥12 months where available; however, if patients achieved complete continence (0 pads per day) prior to 12 months, this was also recorded. Patients who subsequently proceeded to penile prosthesis implantation for ED or artificial urinary sphincter placement for urinary incontinence were also documented.

Statistical analysis

All statistical analyses were conducted using R software (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics were used to summarise patient characteristics and treatment outcomes. Continuous variables are presented as means with standard deviations or medians with interquartile ranges, as appropriate, and categorical variables as frequencies and percentages.

Patient demographics and baseline characteristics

A total of 402 patients were included in this study with a mean age of 64.2 and median follow-up of 23 months (IQR: 14- 38). Metabolic syndrome was prevalent in this cohort with hypertension, dyslipidaemia, diabetes present in 48%, 38% and 18% respectively. The final prostatectomy specimen yielded ISUP Grade Group 2 and 3 in 84.5% with the final histological stage being pT2, pT3a and pT3b in 45%, 41.8% and 13% respectively. Salvage radiotherapy was noted in 17.6%. Table 1 highlights the patient demographic and oncological details.

Table 1: Table shows the baseline, patient demographics, ISUP grade grouping,

Response rate to Erectile dysfunction treatment (Table 2)

Overall, erectile function sufficient for penetrative intercourse was achieved in a subset of patients following treatment, with increasing success observed with escalation from oral to mechanical and injectable treatments, and the highest response rates seen with ICI modalities.

Table 2: Erectile dysfunction treatment utilisation and response following NNS RARP

Phosphodiesterase 5 inhibitors: A total of 301 patients received high-dose PDE5 inhibitors, with only five patients (1.6%) achieving erections sufficient for penetrative intercourse. Lower-dose daily PDE5 inhibitors, in the form of tadalafil 5 mg, were trialled in 168 patients, with no patients achieving erections sufficient for penetrative intercourse.

Vacuum erection device: A vacuum erection device was issued to 333 patients, of whom 73 (22%) successfully applied a constriction ring and achieved penetrative intercourse. Among these patients, six subsequently progressed to penile prosthesis implantation.

Intraurethral alprostadil: Response rates for intraurethral alprostadil were modest (14% for VITAROS and 22% for MUSE), with no statistically significant difference observed between preparations (p = 0.3).

Intracavernosal injections: Overall, 173 patients received intracavernosal alprostadil, of whom 39% achieved erections sufficient for penetrative intercourse. The majority of responders (57/68, 84%) achieved this at doses below the maximum recommended dose, with the remainder requiring titration to the maximum dose of 40 mcg. Conversely, 16% (28/173) of patients failed therapy despite escalation to the maximum dose. Injection-related pain sufficient to deter further use was reported in 18% of patients, and one patient (0.6%) experienced a priapic episode, which was promptly treated. Cumulatively, 26% of patients discontinued therapy or were lost to follow-up.

Response to alprostadil ICI was assessed over the first four postoperative years, with relatively stable response rates observed: 35.4% (28/79) in year 1, 37.3% (19/51) in year 2, 50.0% (13/26) in year 3, and 47.1% (8/17) in year 4. There was no statistically significant difference across time (χ² = 2.26, p = 0.52).

Regarding AvP ICI, 49 patients received treatment, with 41% achieving erections sufficient for penetrative intercourse. Forty-five percent of patients failed to achieve satisfactory erections despite a trial of the maximum dose. Treatment discontinuation or loss to follow-up occurred in six patients (12%), and one patient (2%) experienced priapism. A detailed breakdown of intracavernosal injection outcomes is provided in Table 3.

Table 3: Intracavernosal injections sub-analysis

*Details: 5-hour priapism, settled with aspiration only no phenylephrine)

Combination treatment for ED: A total of 10 patients (2.5%) used combination therapy to achieve erections sufficient for penetrative intercourse. VED were successfully combined with ICI in five patients, with intraurethral alprostadil (Vitaros) in three patients, and PDE5 inhibitors in two patients.

Urinary incontinence outcomes

Urinary continence outcomes at ≥12 months were available for 218 patients. The majority of patients achieved favourable continence outcomes, with 69% reporting complete continence (0 pads per day) and a further 19% requiring only one pad per day, consistent with social continence. Higher degrees of urinary incontinence were less common, with 5% of patients requiring two pads per day and 4% requiring three pads per day. Profound incontinence, use of four or more pads per day, was observed in 2.4% of patients. These findings are summarised in Table 4.

Table 4: Urinary continence outcomes at ≥12 months (N = 218)

Of note, early recovery of continence was observed, with 42 patients (19%) achieving pad-free status by 3 months, increasing to 63 patients (29%) by 6 months.

Prosthetic Surgery

A total of 31 patients (7.7%) underwent or were awaiting penile prosthesis implantation for ED purely after NNS RARP. A further 10 patients, underwent penile prosthesis after NNS RARP and salvage radiotherapy therefore accumulatively 41 patients (10%) had a penile implant. Of these patients, 100% failed PDE5 inhibitors, 98% utilised VED, 90% failed Alprostadil ICI, 66% failed AvP ICI and 32% failed a form of intraurethral Alprostadil. An artificial urinary sphincter was inserted in 11 (2.7%) patients for significant post prostatectomy urinary incontinence purely after NNS RARP (supplementary table 1 for details on incontinence surgery).

This study represents, to our knowledge, the largest contemporary series examining functional outcomes exclusively in patients undergoing bilateral NNS RARP. Our findings demonstrate that erectile function following complete neurovascular bundle resection is markedly impaired, with a median postoperative IIEF-5 score of 2 (IQR 1–4) and only 5 of 301 patients (1.6%) achieving penetrative intercourse with PDE5 inhibitors. Despite this, a subset of patients were able to achieve functional erections with alternative therapies, including 73 of 333 patients (22%) using a VED and 68 of 173 patients (39%) with intracavernosal alprostadil, increasing to 41% with AvP ICI. Overall, 41 patients (10%) ultimately underwent or were awaiting penile prosthesis implantation. These findings highlight that while erectile function recovery is severely compromised following NNS RARP, meaningful functional outcomes may still be achieved in a proportion of patients with appropriate treatment escalation.

Previous literature assessing functional erections after NNS radical prostatectomy remains limited. Krishnan and colleagues reported that 13% of 92 patients achieved functional erections beyond two years following bilateral nerve resection [7]. In contrast, the present study demonstrates negligible response to PDE5 inhibitors in this cohort, with only 5 of 301 patients (1.6%) achieving penetrative intercourse when used as first-line therapy in the postoperative period. It is plausible that a rechallenge with high-dose PDE5 inhibitors at later follow-up might have yielded a modestly higher response rate; however, the retrospective design of this study precluded systematic re-evaluation of previously discontinued therapies, representing an inherent limitation of our analysis.

In contrast, a recent systematic review and meta analysis of PDE5 inhibitors following nerve-sparing radical prostatectomy demonstrated significantly higher rates of erectile function recovery, with improvements in IIEF scores and erectile recovery events observed in approximately 31% of patients [14]. Importantly, all included studies were conducted in nerve-sparing cohorts. This highlights the marked disparity in response observed in our study, reinforcing the limited role of PDE5 inhibitors in the absence of intact neurovascular pathways.

Taken together, these findings suggest that PDE5 inhibitors may have a limited role as early therapy in patients undergoing NNS RARP, with consideration of delayed use or earlier escalation to alternative treatment modalities.

VED promote penile tumescence via negative pressure, induced corporal blood filling and have been shown to preserve penile length, although they do not restore spontaneous erectile function [15,16]. There is, additionally, the potential advantage for motivated patients to apply the constriction ring to facilitate penetrative relations mechanically without the need for pharmacological therapy. Our study demonstrates that approximately one in five men who receive a VED with appropriate tuition use the device for intercourse, while the remainder primarily utilise it for penile rehabilitation. Further research is required to better characterise attrition rates among patients who use VEDs predominantly for rehabilitation.

ICI therapy induces smooth muscle relaxation independent of neural input. In our study, the observed response rates for both alprostadil and AvP ICI injection therapy appear lower than those previously reported [12]. However, this should be interpreted in the context of treatment discontinuation and loss to follow-up, which occurred in 26% and 12% of patients in the alprostadil and AvP groups, respectively. This dropout rate is consistent with the existing literature, where attrition rates for ICI therapy have been reported to range from approximately 30% to 80%, with more contemporary series demonstrating rates of around 30–35% [17-19]. Attrition with ICI therapy has been previously documented, and it is recognised that some patients are unable or unwilling to integrate penile injections into their sexual practices, highlighting the need for alternative treatment options for suitably motivated patients [19].

In our study, injection-related pain was reported by 18% of patients receiving alprostadil ICI, a rate higher than earlier studies [12]. Recent evidence has demonstrated a significant association between injection-related pain and the extent of nerve resection following radical prostatectomy, with patients undergoing NNS procedures shown to have a higher incidence of pain [20]. In that instance, alternatives such as AvP ICI, alprostadil-free Bimix or intraurethral preparations may be appropriate. Intraurethral alprostadil demonstrated modest response in our cohort, with response rates of 14% and 22% for Vitaros and MUSE, respectively. While intraurethral alprostadil has been shown to improve erectile function compared to placebo in mixed ED aetiology cohorts, the available evidence in post-radical prostatectomy patients remains limited and is largely restricted to nerve-sparing populations [21,22].

For patients with refractory ED, penile prosthesis implantation remains a definitive and highly effective treatment option, offering reliable restoration of sexual function and high patient satisfaction rates [23]. In the present study, 7.7% of patients ultimately underwent or were awaiting penile prosthesis implantation for ED. The majority of these patients had failed multiple prior treatment modalities, including oral, mechanical, and injectable therapies.

Bridge et al demonstrated a 65% pad-free rate at 12 months following radical prostatectomy utilising validated questionnaires; however, their analysis did not stratify outcomes by nerve-sparing status [8]. In our study which includes only NNS patients, 69% of patients were pad free at 12 months follow-up. Ultimately, 2.7% of patients received an artificial urinary sphincter for severe stress urinary incontinence.

This study has several limitations. Its retrospective design is subject to inherent biases, and the lack of robust use of validated patient-reported outcome measures limits the ability to objectively quantify functional outcomes across treatment modalities. In addition, the presence of pre-existing mild to moderate ED at baseline suggests that this cohort was comorbid, which may have influenced postoperative functional outcomes. Furthermore, only patients who engaged with postoperative andrology follow-up were included in this analysis, which may introduce a degree of selection bias. It is possible that patients who did not attend andrology services may have had differing priorities, including a lack of interest in sexual activity, or experienced different outcomes, such as minimal symptoms not warranting further care or more complex clinical courses. Detailed oncological outcomes were not captured as part of this analysis. However, this limitation is partially mitigated by the long-term median follow-up and the real-world assessment of treatment success, which reflects sustained functional outcomes that are ultimately meaningful to patients with ED.

Furthermore, reporting the proportion of patients who ultimately require penile prosthesis implantation may provide valuable context for patient counselling, supporting earlier and more integrated discussions regarding prosthetic surgery rather than framing it as the culmination of a prolonged treatment pathway characterised by multiple ED therapeutic failures.

Although the supporting evidence for penile rehabilitation remains limited and heterogeneous, it continues to be widely implemented in contemporary clinical practice and is often applied broadly following radical prostatectomy without stratification by nerve sparing status [13]. In the present study, response to first-line PDE5 inhibitors was observed in only 1.6% of patients, while higher response rates were achieved with mechanical and injectable therapies, including 22% with VED and 39–41% with injection therapy. These findings highlight the limitations of a uniform approach to penile rehabilitation in patients undergoing NNS RARP.

Our data suggest that, if penile rehabilitation is pursued in this cohort, treatment strategies should be aligned with the underlying extent of neurovascular injury, with earlier consideration of therapies that do not rely on intact neural pathways. In this context, VED and intracavernosal injection therapy may represent more appropriate initial treatment options than prolonged use of PDE5 inhibitors alone.

Accordingly, penile rehabilitation strategies should be individualised and guided by nerve-sparing status. As preoperative imaging and intraoperative assessment increasingly allow more accurate characterisation of nerve preservation, there is a rationale for incorporating this information into postoperative ED management [24]. Such an approach may facilitate more appropriate treatment selection, earlier escalation where required, and improved patient counselling, while avoiding prolonged exposure to therapies with a low likelihood of success in patients undergoing NNS RARP.

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