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A significant level 1 evidence base supports Holmium laser enucleation of the prostate as a new gold standard surgical treatment for benign prostatic hyperplasia in all patient scenarios
Tev Aho BHB MBChB FRACS(Urol) FRCS
Cambridge University Hospitals NHS
Cambridge Urology Partnership
Nuffield Health Cambridge, UK
Benign prostatic hyperplasia (BPH) is a common condition in men. It may cause bladder outlet obstruction, resulting in bothersome urinary symptoms and/or urinary retention. Acute urinary retention is painful and necessitates urgent medical attention. Chronic retention is painless, yet potentially dangerous as it can cause backpressure on the kidneys and kidney failure. Increasing medical treatment of symptomatic BPH in the modern era has resulted in fewer men having surgery.
Widespread use of alpha-blockers, which relieve urinary symptoms to a degree but do not affect prostate growth, may be responsible for the fact that men having surgery now are more likely than ever before to have larger prostates and be in urinary retention. Many men do not like being on long-term medications for BPH, and this is expensive to the health economy in the long-term. With the development of laser enucleation and minimally invasive techniques there is potential for resurgence in earlier surgical rather than long-term medical management of BPH.
The history of laser prostate enucleation
Since the introduction of transurethral resection of the prostate (TURP) more than 70 years ago, and open simple prostatectomy (OSP) even earlier, efforts to reduce the morbidity of surgery for obstructive BPH, without compromising its efficacy, have continued. Until the late 1990s the majority of endoscopic approaches involved incising, vaporising or resecting the prostate. In most hands, these techniques leave significant amounts of residual prostatic adenoma in situ, which can cause failure to relieve urinary retention, suboptimal relief of urinary symptoms, recurrent obstruction and prostatic bleeding.
While TURP has remained the endoscopic gold standard in many centres for some time, it is best suited to men with prostates less than 100g in volume. It has long been recognised that OSP, which involves complete anatomical enucleation of the benign prostatic adenoma, leads to a more complete removal of the problematic prostatic adenoma, resulting in greater success in relieving urinary retention, superior improvement in urinary flow and improved durability.
The problem with OSP is its morbidity, which is largely related to bleeding, as well as the abdominal incision. It would seem reasonable to propose therefore, that endoscopic enucleation would be a significant advance. In the 1990s two New Zealand urologists (Gilling and Fraundorfer) realised that the Holmium laser was well suited to endoscopic prostate surgery. They began to vaporise the prostate adenoma using Holmium via a side firing laser fibre in a technique they called Holmium laser ablation of the prostate (HoLAP).
Like all laser vaporisation procedures since, HoLAP was haemostatic but slow and expensive. To save money they cut the ends off the side fire fibres, converting them to multi-use end firing fibres. The end firing fibres allowed bits of prostate to be resected rather than vaporised in a procedure called Holmium laser resection of the prostate (HoLRP).1 Although faster and cheaper than HoLAP, HoLRP remained a relatively inefficient means of adenoma debulking. It was soon appreciated that the adenoma could be completely enucleated using the Holmium laser, and with the development of a tissue morcellator to remove the enucleated lobes from the bladder, the goal of endoscopic enucleation in the form of Holmium laser enucleation of the prostate (HoLEP), had been achieved.2
Level 1 evidence for HoLEP versus the previous gold standards
HoLEP has one of the most extensive level 1 evidence bases of any BPH procedure. There are four published meta-analyses and 16 randomised trials (RTs) comparing HoLEP to the previously recognised gold standards, and a variety of other techniques.
In the largest of the meta-analyses featuring HoLEP, it is compared to mono and bipolar TURP, bipolar transurethral vaporisation of the prostate (TUVP) and green light laser photoselective vaporisation of the prostate (PVP).3 Only HoLEP showed superior symptom and flow rate improvement in comparison to monopolar TURP, and also had fewer immediate complications and shorter hospital stay.
Consistent findings of the eight RTs comparing HoLEP to TURP for standard size prostates include the following benefits for HoLEP:
A significant advantage of HoLEP over all other endoscopic procedures is that it is equally as safe and effective for very large prostates as it is for standard sized prostates. This has been demonstrated in the three RTs comparing HoLEP to OSP that all report less bleeding, shorter catheter time and hospital stay for HoLEP, whilst maintaining equivalent symptom and urodynamic outcomes and durability to at least five years.4
Challenges for BPH surgery in the modern era
Men having BPH surgery in the current era are more likely than ever before to have large prostates, be in urinary retention and to be taking anticoagulant medication. Of all the procedures in the current surgical armamentarium, laser enucleation is the most capable of dealing with all of these scenarios.
The only safe and effective alternative to OSP for the surgical management of very large prostates (>120g) is endoscopic enucleation. A number of published case series and the three RTs described previously versus OSP describe the use of HoLEP for large prostates. They unanimously conclude that HoLEP is safe and effective for prostates of any size, and that there is no upper prostate size limit. The series describing HoLEP for the largest prostates yet reported (mean preoperative prostate volume=218cc), described outcomes equivalent to those in standard size prostates.5
Previous reports for TURP in urinary retention patients warn of significant failure rates of around 20–30%. The UK National Prostatectomy Audit also found that TURP for retention was associated with a significantly increased risk of death compared to TURP for men who were not in urinary retention.6 These data may deter urologists from offering TURP to men in urinary retention. Laser vaporisation appears to suffer from similar failure rates to TURP when used for men in urinary retention. In a study comparing HoLEP to green light PVP for retention patients, 99% of the HoLEP group were urinating spontaneously at six months compared to 74% of the PVP group.7 Another study reported a 98% return to spontaneous urination following HoLEP regardless of preoperative bladder function.8 The fact that HoLEP is capable of better urodynamic relief of bladder outlet obstruction than TURP as reported by Tan et al., is consistent with the more recent reports of excellent outcomes for retention patients after HoLEP.9
More than a third of men having BPH surgery are on some kind of anticoagulation medication. Although not bloodless, HoLEP can be done without stopping clopidogrel and warfarin although there is an increased risk of requiring transfusion, which was reported at 8% by Elzayat et al.10 This is similar to the blood transfusion rate of monopolar TURP in men with normal coagulation.
Endoscopic enucleation using alternative energy sources
Until recently endoscopic enucleation has almost exclusively been performed using a high-powered Holmium laser (Lumenis Inc). The impressive evidence base that supports HoLEP as a new gold standard has resulted in other companies promoting the use of alternative energy sources for endoscopic enucleation. A current pertinent question is whether any other energy sources can equal or better high-powered Holmium. Several recent RTs shed some light on this question:
Neill et al. found that bipolar enucleation (Gyrus) was associated with more bleeding, longer operating and recovery room time, and more use of postoperative bladder irrigation than HoLEP but that long-term outcomes were equivalent. They noted that the surgical view was impaired when using bipolar due to increased bleeding and bubbles.11
Zhang et al. compared Thulium and Holmium for enucleation. The Thulium group had longer operating times and the operative view was clearer and the enucleation effect easier to achieve with Holmium. There were no significant differences in any clinical outcomes to 18 months.12 In a RT of HoLEP versus green light laser vapoenucleation, GreenLEP removed significantly less of the prostate adenoma, and was more expensive than HoLEP due to the use of the obligatory expensive single use fibres compared to the Holmium fibres that individually can be used for up to 30–40 cases. Urinary flow rates were higher in the HoLEP group at 12 months.13
Recent developments in minimally invasive BPH techniques
Several novel minimally invasive treatments for symptomatic BPH have emerged in the last few years.
Prostatic urethral lift (PUL) involves the endoscopic placement of implants into the lateral lobes of the prostate to pull them apart, thereby widening the lumen of the prostatic urethra. The attraction of this concept is that it can be done quickly, as a day-stay procedure, with minimal risk of sexual dysfunction and incontinence. The disadvantages are that it has not been evaluated in the treatment of urinary retention, has not been reported in anticoagulated patients, and is only recommended for patients with minimal enlargement of the lateral lobes of the prostate.
These represent a small proportion of men currently having surgical treatment for BPH, and it will be interesting to see if PUL will encourage men who have previously relied on medical treatment to consider having a procedure instead. A RT comparing urolift to a sham procedure reported greater improvements in symptom scores and urodynamic parameters for urolift, however these were significantly less than those previously reported for endoscopic vaporisation, resection and enucleation. There was less effect on sexual function and incontinence with PUL than has been reported for other endoscopic procedures. It is not expected that PUL will prove durable in the long-term, but multiple treatments or conversion to a later alternative surgical procedure would be technically feasible, although this would impact on the cost-effectiveness of PUL.14
Prostatic artery embolisation (PAE) leads to ischaemic necrosis and resorption of the prostatic adenoma. A RT comparing PAE to TURP reported less improvement in symptoms and urodynamic parameters, and more clinical failures and side effects for PAE.15 Some worrying complications including bladder necrosis have been reported.
Current experience and evidence suggests that HoLEP is a new gold standard for the surgical management of BPH in all patient scenarios. The challenge is to train more urologists to perform it. Urolift is less invasive than HoLEP, and levels of improvement in symptoms and urodynamic parameters are more akin to medical than surgical treatments. It is only suitable for a well selected group of patients. It is seen as an intermediate option between medication and surgery, and is unlikely to result in durable outcomes. Whether this will prove to be cost-effective in the long-term remains to be seen.