NeuroSAFE procedure for RARP leads to improved erectile function

Patients who underwent nerve -sparing during robot-assisted radical prostatectomy (RARP) guided by the NeuroSAFE technique demonstrated improved erectile function at 1 year compared with patients who underwent standard RARP, according to findings from the phase 3 NeuroSAFE PROOF trial (NCT03317990).^1,2

The NeuroSAFE technique also led to improvements in urinary continence at 3 months, but this benefit was not sustained.

The data were presented at the 40th Annual European Association of Urology Congress in Madrid, Spain and published in Lancet Oncology.^1,2

Greg Shaw, BSc, MBBS, MD, FRCS(Urol)

“When we perform robotic radical prostatectomy, we perform a balancing act, balancing the opportunity to remove the cancer and cure it with the potential [adverse events] that come from removing important functional tissue that's closely approximated to the prostate,” explained presenting author Greg Shaw, BSc, MBBS, MD, FRCS(Urol), of the University College of London, United Kingdom. “We tend to err on the side of oncological control. Many patients who have organ-confined disease on the definitive pathology have non-nerve sparing surgery; we don't spare nerves when we could have. The NeuroSAFE procedure is an intraoperative frozen section technique. The surgeon gets feedback in real time during the operation. Having performed a nerve spare, they get to find out if that's resulted in a significant positive surgical margin, which may represent an issue with oncological control. It gives them an opportunity to regain that oncological control by performing a secondary resection.”

In total, the investigators enrolled 407 patients across 5 centers in the UK. Participants were randomly assigned 1:1 to receive NeuroSAFE RARP (n = 204) or standard RARP (n = 203). Following the procedure, 190 and 191 patients comprised the modified intent-to-treat population in each arm, respectively.

Data showed a longer operative time with the NeuroSAFE procedure vs with standard RARP. Specifically, the average surgical time was 174.4 minutes in the NeuroSAFE arm vs 131.4 minutes in the standard arm.

However, Shaw noted during the presentation, “That investment of time translated to an increase in the amount of nerve sparing that we were able to perform.”

Overall, 82.1% of patients in the NeuroSAFE arm were able to receive bilateral nerve-sparing compared with 56.4% of patients in the standard arm.

Patients in the NeuroSAFE arm also reported better erectile function at 12 months based on International Index of Erectile Function (IIEF-5) scores. Specifically, the average IIEF-5 score was 12.7 among patients in the NeuroSAFE arm vs 9.7 in the standard RARP arm (adjusted mean difference, 3.18; 95% CI, 1.62 to 4.75; P < .0001).

Put another way, at 12 months following surgery, 38.7% of patients in the NeuroSAFE arm reported no or mild erectile function, compared with 22.8% of patients in the standard arm. Conversely, severe erectile function was reported in 38% of patients in the NeuroSAFE arm vs 56% of patients in the standard arm.

Measures of urinary continence at 3 months also favored the NeuroSAFE arm. The average ICIQ score was 5.8 in the NeuroSAFE arm vs 7.4 in the standard arm (adjusted mean difference, -1.41; 95% CI, -2.42 to -0.41; P = .006). However, this benefit was not sustained at 6 months, with an average score of 4.5 in the NeuroSAFE arm vs 5.1 in the standard RARP arm (adjusted mean difference, -0.37; 95% CI, -1.35 to 0.62; P = .46).

Oncological outcomes were similar between the 2 arms at 12 months. However, Shaw cautioned during the presentation, “We acknowledge that 12 months is a very early end point for oncological outcomes in prostate cancer. We will report on subsequent time points as our data matures.”

Specifically, prostate-specific antigen (PSA) persistence was observed in 3.8% of patients in the NeuroSAFE arm and 2.7% of patients in the standard arm. Similarly, biochemical recurrence was reported in 5.5% and 3.7% of patients, respectively.

However, the receipt of adjuvant treatment was shown to be higher in the NeuroSAFE arm (4.4% vs 1.1%). Shaw noted, “It's worth bearing in mind that this is treatment that is administered on the perception of adversity based on a pathological report. This is not driven by PSA. It's also no longer recommended practice.”

The investigators then conducted a pre-defined subgroup analysis to assess outcomes among those who would not typically have received bilateral nerve-spare. Among these patients, the average erectile function score per IIEF-5 was 12.6 in the NeuroSAFE arm (n = 120) compared with 8.7 in the standard arm (n = 114) at 12 months following surgery (mean difference, 4.4; 95% CI, 2.63 to 6.26; P < .001). There was no significant difference between the 2 groups in urinary continence scores at 3 months.

“Our results show that by using NeuroSAFE, nearly twice as many men don’t have to face potentially life-changing loss of erectile function after prostate surgery,” concluded Shaw in a news release on the findings.³ “It is an involved procedure that requires expertise, but it isn’t expensive, particularly given the benefits it offers for patients, and most importantly doesn’t jeopardize cancer control. NeuroSAFE wouldn’t be appropriate for all patients, as many can safely have nerve-sparing surgery using standard robotic techniques. But for younger patients and those who wouldn’t normally be seen as eligible for nerve-sparing surgery, it offers them a greater chance to hold onto their quality of life.”

REFERENCES

1. Almeida-Magana R, Dinneen E, Al-Hammouri T, et al. NeuroSAFE versus standard robot-assisted radical prostatectomy (NeuroSAFE PROOF): a randomised, controlled, patient-blinded, IDEAL stage 3 trial. Presented at: 40^th Annual European Association of Urology Congress. Madrid, Spain. March 21-24, 2025. Abstract GC9

2. Dinneen E, Almeida-Magana R, Al-Hammouri T, et al. Effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence in patients with localised prostate cancer (NeuroSAFE PROOF): a multicentre, patient-blinded, randomised, controlled phase 3 trial. Lancet Oncol. 2025. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00091-9/fulltext

3. Twice as many men recover erectile function after improved prostate cancer surgery. News release. European Association of Urology. March 24, 2025. Accessed March 27, 2025. https://www.eurekalert.org/news-releases/1077548