A technique to improve the precision of prostate cancer surgery means that almost twice as many men preserve their erectile function compared to those undergoing standard surgery, according to results from a clinical trial led by researchers from UCL and UCLH.
The results of the NeuroSAFE PROOF trial, presented at the 2025 European Association of Urology (EAU) Congress in Madrid and published in The Lancet Oncology, raise the prospect of major quality of life improvements for men undergoing surgery for prostate cancer, which can often result in erectile dysfunction and urinary incontinence.
The trial evaluated a method (called NeuroSAFE) of preserving the nerves that run through the prostate's outer layers, which are thought to be responsible for producing erections, during prostate removal. The pioneering method includes an additional test to ensure that all of the cancerous cells are removed, so that preserving the nerves does not risk the surgery's success.
In recent years, preservation of these nerves has been made possible by robotic surgery technology that gives the surgeon the precision required to peel off and retain the outermost layers of the prostate where the nerves are situated, a process known as 'nerve sparing'.
However, during standard surgery it can be difficult to determine whether retaining these outer layers risks leaving some cancerous cells behind. In many cases, especially where the tumour is most advanced, surgeons will err on the side of caution and forego nerve sparing to ensure that all of the patient's cancer is removed.
NeuroSAFE enables them to check during the operation whether further tissue removal is needed or not.
Professor Greg Shaw, the trial lead from UCL Surgery & Interventional Science and Consultant Urologist at UCLH, said: "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. 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 jeopardise 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."
The NeuroSAFE PROOF trial, run across five UK hospitals, is the first randomised, controlled trial to fully evaluate the impact of the NeuroSAFE technique on erectile dysfunction and urinary incontinence - two of the most common side effects of prostate surgery.
The trial analysed outcomes for 344 men diagnosed with prostate cancer who were due to undergo prostate removal and who had no prior issues with erectile dysfunction. Half were randomised to receive NeuroSAFE during their operation and half had standard surgery.
Twelve months after surgery, 39% of men in the NeuroSAFE arm had no or mild erectile dysfunction. In those men who had standard surgery this was 23%.
A year after their operation, only 38% of those who had surgery using NeuroSAFE had severe erectile dysfunction, compared to 56% of men who had standard surgery.
The technique did not increase the overall proportion of patients who eventually returned to being fully continent at 12 months. However, NeuroSAFE patients who recovered their urinary control did so faster than patients who underwent standard surgery.
In the NeuroSAFE technique, which has been available for over a decade but is not widely used outside of private healthcare and in Germany where the technique was invented, the surgeon extracts the prostate gland while preserving the maximum amount of nerve tissue around it as possible. The prostate is then flash frozen and samples of it are examined by a pathologist while the operation is still underway. If cancer is found at the edges of the prostate, around where key nerves are situated, the surgeon can then remove additional tissue, sacrificing the nerves but achieving a complete removal of the tumour. If no cancer is found the operation is complete.
This additional step to rapidly examine the prostate means that more patients are able to benefit from nerve sparing, while still ensuring that all of the cancer will be removed.
Dr Ricardo Almeida-Magana, lead author on the Lancet Oncology paper from UCL Surgery & Interventional Science, said: "NeuroSAFE offers surgeons a real time evaluation of the safety of the procedure. In standard robotic surgery, surgeons determine whether to choose nerve sparing based on MRI scans, on digital rectal examinations and on biopsy results prior to surgery.
"But whereas those methods can provide guidance, NeuroSAFE provides certainty. And that opens up the option of nerve-sparing surgery for many more men, without compromising on the chances of controlling the cancer."
Courtney Ming, a 62-year-old from East London who participated in the trial, was diagnosed with prostate cancer in 2015, after reluctantly following his coworker's advice to get tested for prostate issues (PSA test). He later underwent surgery to remove the cancer and benefitted from nerve sparing.
He said: "Now, every year, I do my blood test, and seeing my PSA at 0.01 is a clear indicator that life is good. As a 62-year-old man, my quality of life is still high. If I had to put a percentage on it, I'd say I'm at 85-90% of where I was before surgery. Some days, I feel even better. Most importantly, I'm alive, healthy, and still enjoying life.
"One of the scariest things about this journey was that I had no symptoms. No pain, no waking up in the night to use the bathroom - nothing. Prostate cancer is a silent assassin, and that's why awareness is so important. I'm grateful I listened to my coworkers back in 2015. If I hadn't, I might not be here to share my story today."
Derya Tilki, a member of the EAU Scientific Congress Office and Professor of Urology at the Martini Klinik Prostate Cancer Center in Hamburg, Germany, where the NeuroSAFE technique was developed, said: "We use NeuroSAFE for most of the 2,500 prostate cancer patients we treat each year and it's great to see the technique assessed in a randomised controlled trial for the first time. The results are as we would expect: NeuroSAFE allows more patients to have nerve sparing and that results in better recovery of erectile function. Post-surgical penile rehabilitation for patients can affect erectile function as well, so that is an aspect that also needs to be considered.
"This trial wasn't designed to look at longer term cancer outcomes but based on the data we have from using the technique for over 20 years, NeuroSAFE does not appear to affect these. It would be really valuable to have that confirmed in another randomised trial."
The authors would like to acknowledge the support of surgical teams across all participating sites. They are particularly grateful to the UCLH robotic urology team consisting of Justin Collins, Nicolo De Luyk, Anand Kelkar, Senthil Nathan, Prash Patel, Prabs Rajan, Prasanna Sooriakumaran, Veeru Kasivisvanathan and Ashwin Sridhar.
The study was funded by the National Institute for Health and Care Research (NIHR) Research for Patient Benefit programme, The Rosetrees Foundation, St Peter's Charitable Trust and the Jon Moulton Charity Trust. The hospitals involved in the trial were: University College London Hospitals NHS Foundation Trust, North Bristol Hospitals NHS Trust, Nottingham University Hospital NHS Trust, Sheffield Teaching Hospitals NHS Trust, and Greater Glasgow and Clyde NHS Trust.
