Anatomical Endoscopic Enucleation of the Prostate: An Overview

Abstract

Lower urinary tract symptoms (LUTS) increase with age, primarily due to benign prostatic obstruction (BPO), affecting about 80% of men above 80 years of age with a significant impact on quality of life (QoL). Treatment varies from pharmacotherapy to surgery based on the severity of LUTS. Transurethral resection of prostate (TURP) has been considered the standard of care for surgical management of LUTS/BPO. However, in the last few decades with technological advancements and shortfalls of TURP, newer techniques for surgical treatment have emerged. These techniques score over TURP in many ways providing significant functional improvements, shorter hospital stays, and lower complication rates compared to conventional resection techniques. Advancements in laser technology and surgical approaches have established anatomical endoscopic enucleation of the prostate (AEEP) as a gold standard for benign prostatic hyperplasia (BPH) surgery. AEEP offers excellent functional outcomes, reduced bleeding risks, shorter catheterization times, and lower hospital stays, making it suitable for a wide range of patients, especially those with large prostates. Long-term functional outcomes of AEEP are superior to TURP irrespective of the technique or energies used. Future research should aim to optimize surgical techniques, explore ejaculatory-sparing approaches, and standardize outcome reporting to further solidify AEEP’s role in BPO treatment.

1. Introduction

The prevalence of LUTS increases with age, and it is predominantly due to BPH in men, which ultimately impairs QoL [1, 2]. Approximately 80% of men over the age of 80 years old experience LUTS. LUTS interfere with daily functioning, and elderly males with LUTS often feel emotional discomfort, such as depressive mood and anxiety [3]. The severity of LUTS and the risk of progression determines the choice of therapy in BPH. Pharmacotherapy for BPH has shown a morbidity of >10% in one of the reported studies [4]. Indications for the surgery include failure of medical therapy to reduce bothersome LUTS, intolerable pharmaceutical side effects, or the desire by the patient to avoid taking long-term medical management. Other absolute indications for the surgical treatment are acute and/or chronic renal insufficiency, refractory urinary retention, recurrent urinary tract infections (UTIs), recurrent bladder stones, and recalcitrant gross hematuria [5].

Removal of the obstructing prostatic adenoma by open surgical enucleation, open prostatectomy (OP), is the oldest surgical treatment modality for moderate-to-severe LUTS secondary to BPH. OP reduces LUTS by 63–86%, improves IPSS-QoL score by 60–87%, and increases maximum flow rate (Qmax) by 375% with a reduction of post-void residue (PVR) by 86–98% [6]. Despite excellent clinical outcomes and long-term efficacy, several decades ago, OP was replaced by TURP. It was due to advancements in endoscopic equipment and reduced peri-operative morbidity following transurethral resection. TURP is still regarded as the standard surgical procedure for the treatment of LUTS secondary to BPO in small to medium (30-80 grams) prostates. No studies on the optimal cut-off value exist, but the complication rates after TURP increase with prostate size [7]. Transurethral (TUR) syndrome, bleeding, and infectious complications in the perioperative period following monopolar TURP (M-TURP) were the main reason to look for alternate sources of energy to be used in transurethral procedures which can be equally efficacious with minimum morbidity [8]. Bipolar TURP (B-TURP) has similar efficacy as compared to M-TURP but with lower peri-operative morbidity. Long-term results (up to 5 years) for B-TURP showed that safety and efficacy are comparable to M-TURP [9].

Newer minimally invasive surgical treatment options for BPH have developed in the last three decades. Holmium laser enucleation of the prostate (HoLEP) was introduced in 1998 [10] marking the beginning of interest in endoscopic enucleation for the treatment of BPH. HoLEP proved to be safe and effective, especially in large prostates in many studies [11, 12]. Even non-laser energy like bipolar electrocautery, which was being used for the resection of prostatic adenoma, was found to be effective in the endoscopic enucleation of the prostate [13]. Laser energies like thulium yttrium-aluminum-garnet (YAG), potassium-titanyl-phosphate (KTP), and diode were initially used for vaporization or resection of the prostatic adenoma. The use of end-firing fibers in thulium/diode/greenlight lasers and concepts of separating prostate adenoma from the capsule in the proper surgical plane for enucleation established the fact that the technique of enucleation was more important than the energy used for enucleation [14]. The acronym anatomical endoscopic enucleation of the prostate (AEEP) was coined by Hermann in his editorial [15]. It became “standard of care” in the surgical treatment of BPH once it was included as a treatment of choice in many guidelines [16]. The major advantage of AEEP is the ability to remove the adenoma close to the anatomical plane between the surgical capsule and the adenoma. It is similar to what the index finger does during an OP procedure making it equally efficacious. Several studies demonstrated no significant differences between AEEP and OP in short and intermediate-term functional outcomes. The requirement of blood transfusion was significantly less with AEEP compared to OP [17, 18].

The overall morbidity of TURP is not statistically significant compared to minimally invasive treatment modalities, but the possibility of TUR syndrome is higher with M-TURP. The diversity of possible complications after TURP leads to an increased cumulative risk of adverse events. According to a meta-analysis published in 2010 [19], the most relevant complications include bleeding requiring blood transfusion (2%; range: 0–9), TUR syndrome (0.8%; range: 0–5), acute urinary retention (AUR) (4.5%; range: 0–13.3), clot retention (4.9%; range: 0–39), and UTI (4.1%; range: 0–22). However, the size of the prostate and surgical experience plays a major role in TURP-related complications.

Endoscopic enucleation of the prostate (EEP) procedures remove a maximum amount of prostatic tissue, which is equivalent to open enucleation leading to complete resolution of obstruction. Enucleation is beneficial compared to resection in reducing hospital stay, hemoglobin loss, serum sodium decrease, blood transfusion rate, grade II, grade III complications, and early postoperative complications [20]. A study published by Madersbacher et al. [21] in 2005 reported a cumulative incidence of secondary TURP procedures of 2.9, 5.8, and 7.4% at 1, 5, and 8 years, respectively, following the procedure. HoLEP is the most widely analyzed and reported endoscopic enucleation procedure. The risk of re-operation following HoLEP was variable in different published studies [21]. An interesting meta-analysis [22] published in 2020 reported that there was no statistical difference in functional outcomes following the use of laser or non-laser energy sources for EEP. However, the overall weight of the prostatic tissue enucleated was higher (no clinical significance) and hemoglobin drop was lower when laser energy source was used.

The surgical treatment for LUTS seems to be safe for all age groups as the mortality after any transurethral procedures was found to be less than 0.5%. AEEP has marginally less mortality compared to TURP. Higher postoperative mortality is believed to be associated with increasing age, high Charlson Comorbidity Index (CCI) score, and atrial fibrillation as independent risk factors [23]. It is strongly recommended to carefully consider the type of surgical procedure and weigh the risks and benefits on a case-to-case basis.

2. The evolution of AEEP

Many medical technologies have evolved because of cumulative selection, and EEP is no exception. TURP has been the gold standard surgical treatment for BPH for decades. However, the morbidities following TURP, such as risk of TUR syndrome, bleeding complications, and limitations of resection for large prostate size (>100 grams), were the driving factors to shift to EEP. The first transurethral prostate enucleation was reported by Hiraoka and Akimoto in 1989 [24]. They reported a case series of 200 patients in which a bespoke blade was used to detach the adenoma from the prostate capsule.

A feasible transurethral endoscopic enucleation procedure could once again become a possibility with the advancement and application of laser technology in urology. Gilling and Fraundorfer [25] developed the HoLEP technique in Tauranga, New Zealand, in the mid-1990s. The evolution of this technique which started as an ablative procedure to the current enucleation one is due to the advances in the morcellation techniques and laser technology. Before holmium laser, neodymium: Yttrium-aluminum-garnet (Nd: YAG) laser was used for vapo-laser ablation of prostate (VLAP). It did not gain much enthusiasm due to concerns like delayed time to voiding and post-surgery dysuria. To overcome these shortfalls, Gilling et al. in 1994 introduced hybrid/combination endoscopic laser ablation of the prostate (CELAP) technique using the Nd:YAG laser for circumferential coagulation followed by holmium laser ablation. Thus, a 60-watt laser with a single-use, side-firing fiber was used to vaporize the prostate’s surface in the first pure holmium-only laser ablation of the prostate (HoLAP) in 1994 [25]. The advantages of this procedure were good hemostasis, short hospital stays, and an easy learning curve; however, cons included longer operative times, higher cost, and no tissue available for histopathology. To minimize the cost, Gilling et al. introduced reusable end firing fibers and used them to resect the prostate; hence, the technique of Holmium Laser resection of prostate (HoLRP) was developed. During this evolving process, it was also realized conceptually that a plane between the prostate adenoma and the prostate capsule could be created endoscopically with ease, much like a surgeon’s finger shelling out an adenoma during an open retropubic prostatectomy. Hence, the term HoLEP was coined. Four key steps of HoLEP included: (1) creation of bladder neck incisions, (2) enucleation of the median lobe, (3) enucleation of the lateral lobes, and (4) transurethral morcellation. Initial results showed equivalent outcomes as compared to TURP and better feasibility in larger prostates (>100 g). Many improvements for tissue morcellators developed leading to increased acceptability of this technique among urologists. Various modifications in the way enucleation was done have been described in the literature, for example, mushroom technique, en-bloc enucleation with all achieving the same overall results [13, 26].

Different energy sources were used following the same principles of HoLEP. In early 2000s, bipolar electrocautery was used for vaporization of prostate tissue. In 2006, Neil et al. [13] presented a randomized control trial between HoLEP and plasmakinetic bipolar enucleation of the prostate, which was found to be feasible with similar outcomes. The popularity of transurethral enucleation of the prostate using bipolar energy (TUEB) grew in Asia (especially China), and various modifications in the technique and instruments evolved over time. Liu et al. [27] published their study of transurethral enucleation and resection of the prostate (TUERP) with plasmakinetic energy in 2010. He popularized the concept of using mechanical energy (tip of the resectoscope) for the enucleation of adenoma in proper anatomical plane, coagulating the feeding blood vessels and creating large, detached adenomas which were attached to the prostatic fossa at the bladder neck. These almost avascular adenomas were then resected with the bipolar electrocautery to complete the procedure. The aim of the procedure was to use single set of instruments to do the entire job, avoid morcellation procedure, and hence reduce the cost of treatment. Transurethral enucleation with bipolar (TUEB) using the transurethral resection in saline (TURis) system (Olympus) and the TUEB loop was developed by Olympus Corporation (Tokyo, Japan). Ken Nakagawa introduced the TUEB technique, by using the novel TUEB loop [28]. This bipolar electrocautery loop with enucleating spatula was useful for resection and enucleation with normal saline as irrigation. TUEB results were better than standard TURis technique, especially in large prostates. The ‘button’ type vapo-resection electrode (Olympus Europe, Hamburg, Germany) was designed to use for vaporization of the prostate. But it was soon realized that, the button has enough strength to be used for mechanical enucleation of the adenoma off the capsule. The plasma-button enucleation technique, termed as bipolar enucleation of the prostate (BPEP), was reported to have significantly lower peri-operative morbidity and an improved post-operative recovery when compared with standard OP [29].

In 2005, Xia et al. [30] were the first to describe a technique using the thulium laser for resection of the prostate, whereby the prostate was cut into slices in what they termed the ‘tangerine technique’. Bach and Hermann et al. [31] described the vapo-resection of prostate in 2005, using the thulium laser system. In 2010, Herrmann et al. [32] described the three-lobe technique for thulium laser enucleation of the prostate (ThuLEP) with comparable functional results as HoLEP.

Greenlight laser prostate surgery was first described with a so-called, photo-vaporization of prostate (PVP) technique [33]. One of the limitations of PVP is the challenge encountered in large-volume prostates (>90 ml) in completely vaporizing the transitional zone. With PVP, operating times are longer, and retreatment rates can be as high as 9%. In 2015, Gomez Sancha et al. [34] described greenlight laser enucleation of the prostate (GreenLEP) to overcome these problems. It involved logical steps from standard vaporization to anatomic vaporization, then to vapo-enucleation, and finally to en-bloc enucleation. GreenLEP is a newer enucleation technique, and there is still a paucity of data concerning the long-term effectiveness of this approach.

The 982 nm wavelength high power diode laser was introduced in 2009 for rapid ablation of the prostate tissue [35]. The Eraser laser with a 1318 nm diode laser was found to be effective for cutting, coagulating, and sealing. It was compared with high-power PVP laser for ablation. Lusardi et al. [36] explored the use of this laser for prostate enucleation and reported it to be safe and effective for EEP. Diode laser enucleation of the prostate (DiLEP) for the treatment of BPH when compared with bipolar enucleation was non-inferior at one-year follow-up [37, 38].

The technique of AEEP has evolved over the last two decades. There is more than enough evidence to support its efficacy and safety in the surgical treatment of BPH.

3. Why choose AEEP over TURP?

TURP has remained ‘the gold standard’ in the surgical management of benign prostatic enlargement (BPE) for decades. Many different modalities for the surgical management for BPE have been suggested in recent times. AEEP has stood out as one of the best options for many reasons. It primarily differs from TURP in that the entire adenomatous tissue is removed.

During TURP, one encounters bleeding vessels in most of the swipes as one resects through the adenomatous tissue, whereas in AEEP, blood vessels are encountered only on the inner surface of the peripheral zone as they perforate into the transitional zone. In a meta-analysis done by Wroclawski et al. in 2020, it was concluded that there was a statistically significant difference with reduced drop in hemoglobin, a lesser requirement of blood transfusions, shorter catheter time, shorter hospital stay in AEEP as compared to resection techniques [22].

One of the most important and widely accepted advantages of AEEP is in large prostates. The larger the prostate, the portion of the transitional zone (TZ) removed may be smaller, and the inter-surgeon variability in terms of completeness of adenoma removal is greater in TURP. Therefore, outcomes for vaporization and resection are less good for men with larger prostates. Kuntz et al. [39] reported that surgical re-treatment rates were significantly higher in TURP than those reported for AEEP in men with large prostates at 5-year follow-up. Gilling et al. [40] followed patients in their randomized trial comparing HoLEP versus TURP to a mean of 7.6 years. None in the HoLEP group had required a re-operation compared to 18% in the TURP group. A meta-analysis by Morozov et al. [41] done in 2023 showed that AEEP had a significantly lower re-operation rate and better functional outcomes (Qmax and IPSS) in long term compared with TURP. It may also be beneficial in terms of the International Index for Erectile Function (IIEF-5), PVR, and Prostate Specific Antigen (PSA) levels. Hence, it offers better safety and efficacy for a wider range of patients than any other procedure for prostatic enlargement.

4. The technique of AEEP

In AEEP, removal of the prostate adenoma is done by following a natural anatomical plane. In theory, this procedure when done properly, should be able to achieve maximal efficacy in a minimally invasive manner. Fraundorfer et al. [10] exploited this plane to launch HoLEP in 1998. It was following the same principles of OP carried out by the transurethral route. However, longer operative time, steep learning curve, and fear of urinary incontinence compelled further studies to modify the technique of enucleation. Several investigators used different energy sources (thulium/diode/greenlight lasers, bipolar electrocautery) following the same surgical steps for AEEP.

1. “Three-lobe technique” where two longitudinal incisions from the bladder neck to verumontanum at 5 and 7 o’clock positions are made initially. These two incisions are joined proximal to verumontanum, and the entire median lobe is enucleated in a retrograde manner. Two lateral lobes are then enucleated after separating them by a third longitudinal incision at 12 o’clock position and two vertical incisions distally around the apical region to separate the adenoma from its capsule proximal to the sphincter zone muscle fibers. Three lobes of prostatic adenoma enucleated independently from the prostatic fossa and pushed into the urinary bladder for removal by morcellation [10, 40]. Subsequently, many studies tried to simplify the technique by offering some modifications. Hochreiter [26] described a “mushroom technique” whereby the enucleated prostate adenoma was kept attached to the prostate fossa at the bladder neck which was later resected with electrocautery to avoid a morcellation procedure.

2. “Two-lobe technique” published by Dusing et al. [42] reported that enucleation efficiency can be improved with modification of the technique and experience. A solitary posterior groove is made, and the median lobe is included in the enucleation of one of the lateral lobes, which saves operative time in large prostates. They also advocated the initiation of enucleation at the apex lateral to the verumontanum, as opposed to 12 o’clock anterior, as the plane between the adenoma and capsule is easy to identify around the verumontanum. Dissection is then carried lateral and circumferential to separate the lateral lobes. An early apical release by incising mucosa over the apical region and avoiding stress and strain of mechanical manipulations on the sphincter zone was found to reduce the incidences of urinary incontinence (UI) following this technique.

3. “En-bloc technique” is the modification where all three lobes of the prostate are enucleated as one unit. Enucleation is begun by incising mucosa around verumontanum and defining the posterior capsule. Then, the surgical plane is widened circumferentially and in retrograde fashion from the apical region to the bladder neck. Many variants of “en-bloc” enucleation are reported by different investigators [43, 44] claiming the superiority of their techniques. The ‘en-bloc’ techniques with early apical liberation have emerged with many theoretical advantages: better visualization, faster identification of the surgical capsule and the correct plane to dissect reduced operating time and amount of energy delivered, better preservation of the sphincter, and an improved learning curve compared to the three-lobe technique [45, 46].

Future larger comparative studies are needed to evaluate true impact of the technique on outcomes of AEEP.

5. Energies used for the AEEP

After Fraundorfer et al. [10] described the possibility of EEP with the use of holmium laser in 1998, many researchers tried to use various energy sources for EEP to match the results of HoLEP or improve it further. Much cited editorial [15] by Herrmann in 2016 steered discussion on focusing AEEP as a new gold standard surgical treatment in the BPO. Maximum studies comparing outcomes and complications among all AEEP techniques have been done with HoLEP; on the other hand, GreenLEP is the least studied one. It was soon realized that anatomical knowledge and the technique of enucleation were more important than the energies used for enucleation.

1. The holmium laser has a wavelength of roughly 2140 nm and can penetrate tissue for 0.4 to 0.5 mm. Holmium lasers operate in a pulsed form. High peak pressures have more mechanical effects on the tissues compared to thulium laser. This helps the holmium laser to follow the path of least resistance between the adenoma and the surgical capsule. That may be the reason, HoLEP is considered to be more anatomic. However, many meta-analyses and studies found no significant differences in peri-operative or functional parameters [47].

2. The Thulium: YAG laser transmits energy as a continuous wave with a wavelength close to 2000 nm and its increased affinity for water absorption makes it an excellent vaporizing and cutting laser. ThuLEP uses blunt dissection to a greater extent and laser energy is used as and when it is necessary. The cutting ability of ThuLEP may be beneficial in some situations, as anatomical enucleation is not necessarily required. With the whole range of surgical approaches for transurethral prostatectomy for BPO, including vaporization, resection, enucleation, and vapo-enucleation, thulium:YAG offers the best choice.

3. The diode laser has the strongest tissue penetration capabilities with an effective distance of 5 mm. Its capacity to harm the surgical capsule of the prostate when used for prostate enucleation cannot be disregarded [48]. The diode lasers have the physical properties of a high energy conversion efficiency. Small and portable size of the machine may contribute as favorable factors in their use for clinical practice. The literature lacks robust studies showing comparison of diode laser use for EEP with other widely used lasers like holmium and thulium.

4. The greenlight laser is one of the lasers with good tissue penetration performance, according to an investigation of physical parameters. The thermodynamic conduction distance is 1–2 mm, and its optical visible penetrating ability is 0.8–0.9 mm. At the same time, it works in the continuous mode. Although the mechanical effect can be avoided, the tissue damage caused by the thermodynamic effect of the continuous working mode, and the strong tissue penetration is worthy of attention [34].

5. Bipolar endoscopic enucleation of the prostate (BEEP) includes a large range of procedures, such as plasmakinetic enucleation of the prostate (PkEP), transurethral resection enucleation of the prostate (TUERP), bipolar plasma enucleation of the prostate (BPEP), transurethral vapor-enucleation resection of the prostate (TVERP), transurethral vapor-enucleation of the prostate (TVEP) and, finally, bipolar enucleation of the prostate (BipoLEP). All enucleation procedures with bipolar energy have found to be better than bipolar TURP in terms of efficacy and safety. Many studies have reported bipolar enucleation of the prostate as a safer alternative with equally comparable outcomes with OP or HoLEP [49].

6. The thulium fiber laser (TFL) is an advanced tool suitable for both soft tissue procedures and lithotripsy, utilizing two operational modes: quasi-continuous wave (QCW) and super pulsed (SP). The QCW mode, similar to the thulium:YAG laser, is specifically used for soft tissue surgeries such as the surgical treatment of BPH or non-muscle invasive bladder cancer (NMIBC). The SP mode, akin to the Holmium:YAG laser, applies to both soft tissue and stone surgeries [50]. TFL has a wavelength of 1940 nm with a maximum water absorption peak in tissue. It has a theoretical tissue penetration depth of 100 micron. Since soft tissues are predominantly composed of water (*80%), the thermal effects of TFL make it more precise for cutting compared to holmium laser. Key distinctions between SP TFL and Ho:YAG include SP TFL’s higher potential frequency (up to 2000 Hz compared to Ho: YAG’s 50-80 Hz), lower peak power (500 W for SP TFL vs. 2-10 kW for Ho: YAG), and longer pulse duration (500 milliseconds for TFL vs. 350 milliseconds for Ho: YAG) [51]. The area of coagulation with holmium laser is larger compared to TFL, so no carbonization is seen with holmium laser. TFL appears to be an efficient alternative to Ho:YAG laser for soft tissue surgery. TFL not only boasts beneficial properties for surgical procedures but also offers enhanced usability and serviceability [52]. Its setup is more compact and lighter than the Ho: YAG systems, requiring less space in the operating theater and easing its use. TFL operates on standard 220 V or 110 V electrical sockets, simplifying installation requirements in smaller surgical spaces. Additionally, TFL is quieter during operation, as noted by Moore et al., improving communication among surgical staff during procedures and enhancing the overall comfort for surgeons and nurses [53].

Holmium laser has stood the test of time; it has been extensively studied and has become the gold standard for laser prostatectomy. A contemporary sophistication of the holmium laser has been the development of pulse modulation, in which two consecutive rapid pulses are emitted [54]. This Moses Technology makes it possible to preserve dissection properties and also offers improved cutting plus coagulative effect.

Recent advancements in both thulium and holmium lasers with pulse modulation capacity are a significant leap forward for the safe and efficient AEEP. It is a matter of personal preference regarding which energy source is better for EEP.

6. Learning curve for AEEP

EEP is generally considered more challenging to learn than TURP due to the need for precise identification of the correct tissue layer. Various methods, including step-by-step techniques and newer, potentially simpler approaches, have been proposed to reduce the EEP learning curve. Herrmann [14] noted that prostate enucleation offers consistent efficacy and safety across different energy sources, though no similar claim has been made regarding ease of learning. The learning curve’s length can vary significantly, requiring between 15 and 80 procedures to master [55, 56]. A systematic review done by Kampantais et al. [57] highlighted the critical nature of this learning curve, showing that initial training phases could lead to more frequent relapses and complications, as evidenced by their review of 24 studies on HoLEP.

Mastering HoLEP typically requires performing 30-40 cases, with proficiency plateauing after 20 to 60 cases, though certain efficiencies continue to improve [58]. Lerner et al. [59] found that extended intervals between procedures (over 5 weeks) significantly raise the risk of incontinence, underscoring the need for consistent practice to minimize complications.

A study by Peyronnet et al. [60] comparing GreenLEP and HoLEP found a slightly quicker learning curve for GreenLEP in achieving operative benchmarks, with complication rates stabilizing after 30 cases for HoLEP but remaining consistently low for GreenLEP. ThuLEP and ThuFLEP have learning curves of about 30 and 20 cases, respectively, while TUEB requires 40–50 cases to master [61]. Enikeev et al. noted that methods using electric energy are more challenging to learn than laser techniques, although no specific case number was provided [62, 63]. Xiong et al. observed that inexperienced surgeons might switch from TUEB to bipolar resection in challenging cases, opting to manually cut tissue instead of using morcellation upon enucleation completion [64].

EEP learning curve assessment is varied, often showing a diminishing return pattern as many surgeons have prior endourology experience. While early progress is described as “steep,” implying rapid learning, the term lacks a strict definition. Complication rates and the number of procedures (ranging from 20 to 200 for proficiency) are influenced by the surgeon’s prior experience and the time between cases.

7. Complications of AEEP

AEEP is likely to become a “future standard” in the surgical treatment of BPH. However, peri-operative complications of AEEP are inevitable although the incidence is reducing with refinements of the technique.

Transient urinary incontinence (UI) is a common complication after AEEP, but most patients recover within 3–6 months. The incidence of UI is significantly related to the surgeon’s experience [65]. It was reported that approximately 16.6–29.4% of patients suffered from post-operative UI within 6 months after HoLEP, but only 0–3.3% of patients could not recover automatically at 12 months [66]. Krambeck et al. [67] reported that at short-term, intermediate term, long-term, and greater than 5-year follow-up, stress incontinence was noted in 12.5, 3.4, 1.8, and 4.8% of patients, respectively. The incidence of UI after BipoLEP was 6.8%, among which 91.3% of patients recovered 3 months after surgery and 97.5% of patients recovered 6 months after surgery. Age ≥ 70 years and prostate volume ≥ 90 mL were associated with post-operative SUI [68]. The number of previous surgical cases is a predictor of transient UI, with a higher number of cases associated with a lower incidence of incontinence. Other factors that can predict post-operative incontinence include the IPSS, pre-operative detrusor overactivity (DO), patient’s age, and surgeon mentorship [69].

The overall incidence of peri-operative hemorrhage requiring blood transfusions after AEEP is approximately 1.2-1.9% of BPO patients [70, 71]. Mean hemoglobin before and after HoLEP decreased from 14.6 to 12.3 g/dl, and mean hematocrit decreased from 44.3 to 37.7% [72].

Adverse events after HoLEP are considered quite rare, and most complications develop early during the surgeon learning curve, emphasizing the importance of the mentorship process in improving the surgeon learning curve and reducing potential complications. For instance, the risk of bleeding and blood transfusion is lower for HoLEP than for TURP and open prostatectomy. The transfusion rate of 0.8% reinforces the safety of this procedure even in anticoagulated cases [72].

A bladder neck contracture is another complication of AEEP, with a high recurrence rate. It occurs in about 0.8% of patients undergoing AEEP [73]. The incidence of bladder neck contracture is comparable between different AEEP techniques, such as HoLEP, BipoLEP, ThuLEP, and GreenLEP. The main cause of postoperative bladder neck contracture is mechanical and thermal impairment to the bladder neck during surgery. Other risk factors for bladder neck contracture include pre-operative urinary tract infections, excessive diameter of the device, and prolonged post-operative catheterization. Techniques that preserve the prostatic apex or reduce the tension in the external sphincter can help reduce the incidence of bladder neck contracture as well as maintain ejaculatory function.

With an incidence of 1.2–7.3%, urethral stricture is a complication that can occur after various types of prostatectomies [72, 73]. The incidence of urethral stricture after AEEP is significantly lower compared to TURP and open surgery [72]. However, the incidence of urethral stricture is similar between AEEP techniques such as HoLEP, ThuLEP, and DiLEP [14]. Risk factors for urethral stricture include mechanical impairment, intra-operative incision due to the confined urethral meatus, urinary tract infection, and prolonged catheterization. ​ Pre-operative urethral dilation increased lubricant use, and shortened operation time can help reduce the occurrence of urethral stricture [12].

Sexual dysfunction is another important consideration in BPH surgery. Retrograde ejaculation is the most common sexual dysfunction after AEEP, with a high incidence (>75%). The incidence of retrograde ejaculation is similar between AEEP and TURP [74]. Preserving the bladder neck during surgery may help reduce the occurrence of retrograde ejaculation, but the impact of bladder neck preservation on ejaculation remains controversial. Erectile dysfunction is rarely observed after AEEP. ThuLEP has been shown to have a minimal effect on erectile function, and the power intensity used in HoLEP does not affect erectile function [75].

In conclusion, AEEP is a safe surgical procedure for the treatment of BPH with lower complication rates compared to open surgery and TURP. Transient UI is a common complication, but most patients recover within a few months. Bladder neck contracture and urethral stricture are more serious complications that require further research to develop prevention and treatment strategies. Retrograde ejaculation is a common sexual dysfunction after AEEP, but erectile function is generally preserved. Surgeon experience and technique play a significant role in reducing the incidence of complications.

8. Functional outcomes of AEEP

AEEP is considered technically challenging when compared with TURP. All guidelines outline that it is the experience of the surgeon that has the largest impact on complications and clinical outcomes. Maximum studies comparing outcomes and complications among all AEEP techniques have been done with HoLEP, and on the other hand, GreenLEP is the least studied one. The key outcomes – IPSS, Qmax, reduction in PVR, operation time and complications – were routinely utilized as essential indicators for assessing the surgical therapy of BPH in majority of the studies.

European Association of Urology (EAU) guidelines summary published in 2024 strongly recommends Holmium YAG laser enucleation for large prostates only [76]. Recommendation is weak for thulium YAG laser, and there is insufficient evidence for all other laser-based procedures. Yucheng Ma et al. studied various enucleation techniques by a network meta-analysis (NMA) method [77]. They reported that diode lasers did not exhibit statistically significant advantages or drawbacks over other types of lasers in terms of safety and efficacy. Greenlight laser demonstrated the weakest performance according to this NMA study.

In a prospective and randomized trial with 133 patients, Zhang et al. reported that ThuLEP required longer operation time (72.6 vs. 61.5 min) but resulted in less blood loss compared to HoLEP [78]. However, many meta-analyses reported no significant difference between ThuLEP and HoLEP [79]. ThuLEP was associated with the shortest operative time compared with HoLEP in one of the studies [62]. Enucleated tissue weight was similar in most comparisons, except that one RCT showed that the enucleation weight was lower with GreenVEP compared with that of HoLEP.

Pang et al. in 2022 in their systematic review and meta-analysis of published RCTs comparing various techniques reported that AEEP offers similar efficacy and safety to TURP in small and medium size (30–60 grams) prostates, and it is a better alternative in large prostates when compared to open prostatectomy [47]. Improvement in IPSS, QoL, Qmax, and PVR are similar regardless of energy and technique used for the enucleation of the prostate. On comparing different EEP techniques, ThuLEP significantly improves IPSS and QoL scores more than HoLEP in the short term (1 month), but not in the longer term (12 months). There were no other functional outcome differences in meta-analyses.

Functional outcomes may well be affected by the differences in power settings, variations in the technique, and the type of morcellators used. Where laser facilities are not readily available, enucleation using plasma-kinetic energy is reported to be a good option as most of the outcomes following PKEP are like enucleation using lasers with reduced cost of the treatment.

Gauher et al. [80] in their meta-analysis reported that MoLEP performs better in terms of intraoperative outcomes when compared to traditional HoLEP. However, the difference was not clinically meaningful. It needs long-term data and multicentric trials to recommend it as a replacement for standard HoLEP. A Propensity Score-matched Analysis from the Refinement in Endoscopic Anatomical Enucleation of Prostate (REAP) Registry [81] reported that early and delayed outcomes of enucleation with ThuFLEP are comparable to those with high power HoLEP, with similar improvements in micturition parameters and IPSS. Another similar study by Kamalov AA et al. showed that ThuFLEP was comparable to bipolar enucleation in perioperative characteristics, improvement in voiding parameters, and complication rates [82].

The treatment modalities and recommendations should be tailor-made according to the prostate size, co-morbidities, and sexual needs. Before embarking on the attempts to improve the sexual outcomes of enucleation, its erectile function, ejaculatory function, and orgasmic function results need to be better defined. Exploring different ejaculatory-sparing techniques could be a golden opportunity to further consolidate the role and expand the indications of enucleation surgery. More randomized controlled trials (RCTs) are needed to compare different EEPs, and future research should focus on ‘standardized’ reporting, that is, reporting pre- and post-operative IPSS/IIEF and uroflowmetry parameters and using the Clavien-Dindo system for complications.

9. Conclusions

AEEP provides at least equivalent, and possibly greater improvements in urinary symptom scores, maximum urinary flow rates (Qmax), and PVR compared to vaporization and conventional resection techniques. AEEP has less bleeding and shorter catheter-free time and length of stay. AEEP is strongly recommended in large prostates because of its safety and efficacy. Overcoming the learning curve can be made easier with proper mentorship and guidance. All types of energies used for AEEP give equivalent long-term outcomes; however, HoLEP has the longest duration follow-up data and the largest published evidence in favor of successful outcomes. Newer en-bloc enucleation techniques and energy sources like TFL have promising future. AEEP is a truly well-established, size-independent gold standard, minimally invasive surgical treatment for BPH.

Conflicts of interest

The authors declare no conflict of interest.