Introduction

Although associated with considerable perioperative morbidity, transurethral resection of the prostate (TURP) and open prostatectomy (OP) have been the standard treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) over decades [1, 2]. Since the introduction of holmium laser enucleation of the prostate (HoLEP) into the armamentarium of BPO treatment [3], HoLEP has been proven in numerous randomized controlled trials (RCT) to be a minimally invasive, size-independent method with excellent long-term results [4, 5]. Based on the HoLEP technique, alternative techniques for transurethral endoscopic enucleation of the prostate (EEP) have been described using different energy sources [6]. One prominent representative is the Thulium:YAG laser for thulium vapoenucleation of the prostate (ThuVEP) [7]. Although ThuVEP has been shown to be a size-independent procedure for the surgical treatment of BPO with low perioperative morbidity and good long-term results [8,9,10], RCTs have not been performed so far. The aim of this RCT was to compare the perioperative efficacy and safety between ThuVEP and HoLEP in patients with LUTS secondary to BPO and enlarged prostates.

Methods

After institutional review board approval, an unicentric RCT was performed from January 2015 to February 2016 at the Asklepios Klinik Barmbek. This RCT was registered in the German Clinical Trials Register (DRKS-ID: DRKS00008206). Inclusion criteria were maximum urinary flow rate (Q max) ≤15 ml/s, International Prostate Symptom Score (IPSS) ≥12, male patients ≥18 years, and/or failed medical therapy of BPO, recurrent urinary tract infections (UTI), and/or recurrent episodes of urinary retention. Exclusion criteria were previous urethral/prostatic surgery, known prostate cancer (PCa) or urethral strictures, and urodynamically diagnosed neurogenic bladder.

A total of 107 consecutive patients were randomly assigned in a 1:1 fashion using computer generated block randomization to HoLEP or ThuVEP (Fig. 1). Preoperative assessment included a physical examination with digital rectal examination, prostate volume by transrectal ultrasound, uroflowmetry, measurement of post-void residual urine (PVR), IPSS, quality of life (QoL), PSA assay, urine analysis, and urine culture.

Fig. 1
figure 1

The Consolidated Standards of Reporting Trials (CONSORT) E-flowchart shows the design of the study including randomisation and immediate treatment

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All surgeries were performed by two surgeons (AJG, CN) who had performed more than 500 ThuVEP and 200 HoLEP procedures each. A 26F continuous-flow laser resectoscope in combination with a mechanical tissue morcellator (Wolf Piranha®, Richard Wolf, Knittlingen, Germany) was used. ThuVEP was carried out using a 1940 nm continuous wave Tm:fiber laser (vela® XL, Boston Scientific, Ratingen, Germany) at 90 W, while HoLEP was performed using a 2080 nm pulsed Ho:YAG laser (Auriga® XL, Boston Scientific, Ratingen, Germany) at 39.6 W (2.2 Joule, 18 Hz). A 550-µm bare-ended, re-usable laser fiber was used (LightTrail®, Boston Scientific, Ratingen, Germany). HoLEP and ThuVEP techniques have been previously reported in detail [7, 9, 11]. In brief, depending on the lobe configuration and the size of the prostate, a 2- or 3-lobe technique was performed in ThuVEP and in HoLEP. Briefly, the 2-lobe technique starts with a 5- or 7-o’clock incision with enucleation of one lateral lobe, followed by enucleation of the median and remaining lateral lobe as a single unit. The 3-lobe technique is used in large volume prostates with large median lobes. After 5- and 7-o’clock incisions down to the surgical capsule, the median lobe is enucleated in a retrograde manner. The lateral lobes are enucleated by dissecting the prostatic adenoma from the peripheral zone at the layer of the surgical capsule. ThuVEP and HoLEP were performed using the same 2- or 3-lobe techniques. At the end of surgery, a 22F three-way foley catheter was inserted for continuous bladder irrigation, which was finished the next morning according to standard department protocol. Routinely, the catheter was removed on the second postoperative day. All patients received a perioperative antibiotic regimen with a second generation cephalosporin routinely until removal of the catheter or antibiotics according to an antibiogram. Blood loss was estimated by comparing the hemoglobin value before surgery with the corresponding value on the first postoperative day. Patients were discharged after removal of the catheter and after being able to void adequately.

All medical and surgical complications were noted and classified according to the modified Clavien classification system by four residents not involved in the surgeries (CM, AVB, CT, BB) [10, 12, 13]. All patients were reassessed one month after surgery by IPSS, QoL, Q max, and PVR.

The primary endpoints of the study were IPSS and Q max (ml/s). The secondary endpoints were operation/catheterization/hospitalization time, the complication rate (CR), QoL, and PVR assessments during follow-up. The sample size was calculated for the detection of statistically significant differences for the final analysis 2 years postoperatively. The follow-up is still ongoing and the estimated completion of 2-year follow-up data will be in 2018. With α = 0.05 (type I error, 0.025 adjusted for the 2 primary outcomes) and a power of 90% (β = 0.10), a sample size of 32 patients per group was calculated. The calculation assumed that the relevant difference in IPSS was 3 (SD = 3) and in Q max it was 3 (SD = 6) ml/s. Since an overall yearly dropout rate of about 15% was expected, 45 patients per group had to be recruited.

Using SPSS 22 (IBM Corp, Armonk, NY, USA), the two-tailed χ 2-test or the Mann–Whitney U test were applied to determine the statistical significance of differences between various parametric and non-parametric parameters of the study groups. Improvement in the assessed parameters in each treatment arm was calculated using the paired t test. Patient data were expressed as median (interquartile range). A p value ≤0.05 was considered statistically significant.

Results

Table 1 lists the baseline characteristics of the patients. There were no statistically significant differences in any baseline characteristics between the ThuVEP (n = 48) and HoLEP (n = 46) group. Fifty (53.2%) patients had a gland volume ≥80 ml, with 29 (30.9%) have glands ≥100 ml, respectively (Table 1).

Table 1 Baseline characteristics
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Table 2 lists perioperative data. The operative time was 60 (41–79) minutes without differences between the groups, although enucleation time was significantly shorter for ThuVEP compared to HoLEP (27.3 vs. 40 min, p ≤ 0.004). There were no differences between the groups regarding catheterization time [2 (2–2) days] and postoperative stay [2 (2–3) days].

Table 2 Perioperative data
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Tables 3 and 4 list detailed information on all complications and treatment modalities. Clavien 1 (13.8%), 2 (3.2%), 3a (2.1%), and 3b (4.3%) complications occurred without differences between the groups. The most frequent complications were acute urinary retention (AUR) (8.5%), clot retention without surgical revision (4.3%), surgical revision due to bleeding (3.2%), and UTI (2.1%) (Table 4). The occurrence of postoperative AUR was significantly higher after HoLEP compared to ThuVEP (15.2 vs. 2.1%, p ≤ 0.022). The overall immediate CR was 23.4% (Table 3) and significantly higher after HoLEP compared to ThuVEP (12.5 vs. 33.3%, p ≤ 0.015).

Table 3 Clavien grade 1 to 3b complications
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Table 4 Detailed analysis of Clavien grade 1 to 3b complications within 30-day perioperative period
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At 4-week follow-up, Q max, PVR, and IPSS had improved significantly compared to baseline (p ≤ 0.005) without differences between the groups (Table 5), while QoL was significantly different between ThuVEP [2 (1–3)] and HoLEP [3 (2–5), p ≤ 0.040] (Table 5). One patient (2.1%) in the ThuVEP and 4 (8.7%) in the HoLEP group showed transient urge incontinence (p = 0.149), while 9 (18.8%) in the ThuVEP group and 8 (17.4%) in the HoLEP group had transient stress incontinence after removal of the catheter (p = 0.491). Stress incontinence recovered in all patients within one month. At 1-month follow-up, one patient in the ThuVEP group (2.1%) and one (2.1%) patient in the HoLEP group had urge incontinence.

Table 5 Baseline and follow-up data
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Discussion

The key results of our PRT were that ThuVEP and HoLEP are both safe and effective procedures in patients with LUTS secondary to BPO and enlarged prostates. Both procedures give equivalent and satisfactory immediate micturition improvement with low perioperative morbidity at short-term follow-up.

The major benefit of transurethral EEP is combining the advantages of OP (complete dissection of the prostate adenoma from the prostatic pseudocapsule) with those of the transurethral approach (direct sealing of bleeding vessels). HoLEP was the most outstanding EEP procedure for the surgical treatment of BPO during the past two decades [4, 5]. HoLEP or EEP has been recommended by the current guidelines of the European Association of Urology in men with substantially enlarged prostates (>80 ml) as first-line therapy [14]. However, only few PRT for EEP other than HoLEP [4, 5] and bipolar enucleation of the prostate (BipolEP) [15,16,17,18,19,20,21,22] are available: GreenLight laser enucleation of the prostate (GreenLEP) [23], thulium laser enucleation of the prostate (ThuLEP) [24, 25], eraser laser enucleation of the prostate (ELEP) [26], and diode laser enucleation of the prostate (DiLEP) [22, 27]. One prominent EEP technique is the ThuVEP procedure utilizing the Tm:YAG laser [6,7,8,9,10], but PRT for ThuVEP have not been published yet. We report the first results of a PRT comparing ThuVEP with HoLEP.

An immediate and significant improvement of voiding parameters (Q max, PVR) and symptom scores (IPSS, QoL) after ThuVEP and HoLEP was shown at discharge and continued to do so during 4-week follow-up in our series, comparable to TURP [4, 5], OP [4, 5], HoLEP [4, 5, 15, 23, 24], BipolEP [15,16,17,18,19,20,21], GreenLEP [23], ThuLEP [24, 25], and ELEP [26]. We could confirm that both, ThuVEP and HoLEP, are size-independent procedures, since the median prostate volume was 80 ml with fifty (53.2%) patients having been treated with prostate volumes ≥80 ml. This size-independence of EEP could be already demonstrated in RCTs for HoLEP [4, 5, 23], BipolEP [16,17,18,19,20,21], GreenLEP [23], and DiLEP [22].

Median postoperative stay and catheterization times were 2 days in our series without differences between ThuVEP and HoLEP, which is shorter than in TURP [1, 4, 5, 16] and OP [2, 4, 5, 17,18,19,20,21]. Regarding postoperative stay and catheterization times after transurethral EEP procedures, shorter catheterization times and postoperative stay have been reported in enlarged prostates (≥80 ml) for HoLEP [4, 5, 23], BipolEP [19, 21, 22], and GreenLEP [23], but also longer catheterization times and postoperative stay for BipolEP [17, 19, 20, 22] and DiLEP [22] was shown. In this series, the foley catheter was removed routinely 48 h after surgery and the strategy of keeping the patient in the hospital until able to void adequately was followed. However, catheterization times and hospital stay are most likely triggered by differences in reimbursement in the different national health systems and should be taken into account when comparing these parameters from different series [10].

Interestingly, the enucleation time was significantly shorter in ThuVEP compared to HoLEP. The continuous wave mode of the Thulium:YAG laser might allow a faster enucleation compared to the pulsed mode of the Holmium:YAG laser. On the other hand, the coagulation depth of the Thulium:YAG laser (2 mm) is more shallow compared to the Holmium:YAG laser (4 mm). Therefore, more time might be required for the final coagulation after ThuVEP compared to HoLEP, which might explain why there were no differences between the total operative times of the procedures.

Clavien 1 (13.8%), 2 (3.2%), 3a (2.1%), and 3b (4.3%) complications occurred without differences between the groups. The overall CR was 23.4% and was significantly higher after HoLEP compared to ThuVEP (12.5 vs. 33.3%). This was mainly due to the higher recatheterization rate after HoLEP compared to ThuVEP (15.2 vs. 2.1%), which was a surprising result of our study. One possible explanation would be that the apical detachment of the lateral lobes from the apico-mucosal strip might be different between the thulium laser and the holmium laser. The energy of the Thulium:YAG laser is delivered in a continuous wave mode, which allows clear and smooth incisions, contrary to the pulsed Ho:YAG laser. Therefore, remnants of the apico-mucosal strip might be responsible for the differences in the recatheterization rates. However, the total CR as well as the HoLEP recatheterization rate in our study is well comparable with the literature [4, 5, 15]. Other non-interventional perioperative complications in this PRT were clot retention without surgical revision (4.3%) and UTI (2.1%). These CRs were comparable with current TURP [4, 5] or OP series [4, 5, 18,19,20] and comparable with HoLEP [4, 5], BipolEP [15,16,17,18,19,20,21,22,23], GreenLEP [23], ThuLEP [24, 25], ELEP [26], and DiLEP [27]. To note, the transfusion rate was very low (1.1%), although 18 patients were treated on ongoing anticoagulant therapy in the ThuVEP (n = 9) and HoLEP (n = 9) group. This supports the excellent haemostatic properties of both lasers and ensures the safety of ThuVEP and HoLEP in anticoagulant patients [28, 29]. The overall immediate perioperative reoperation (Clavien 3a/b) rate was 4.3% and mainly consisted of three patients (3.2%) treated with ongoing anticoagulant therapy who required coagulation of the prostate fossa due to postoperative bleeding. Therefore, the reintervention rates were well comparable with HoLEP and ThuVEP series [4, 5, 7,8,9,10, 15, 23] and other EEP procedures such as BipolEP [15,16,17,18,19,20,21,22,23], GreenLEP [23], and ThuLEP [24, 25].

With this study we present the first PRT comparing the ThuVEP procedure with the well established EEP procedure, the HoLEP technique. However, our study has several limitations: The current unicentric PRT was not powered to detect non-inferiority of ThuVEP over HoLEP, which seems to be the main limitation. All procedures were performed by two experienced surgeons (AJG, CN), who had done more than 500 ThuVEP and HoLEP procedures each. This might be a reason for the low Clavien 3a/b (4.3%) CR in this PRT and the low transfusion rate (1.1%), despite of the facts that median prostate size was 80 ml and 19.1% of the patients were treated under ongoing anticoagulant treatment. Finally, all HoLEP procedures were carried out as low powered (39.6 W) HoLEP and compared to 90 W ThuVEP. A RCT comparing low powered with high powered HoLEP has not been published so far. The only difference in clinical parameters found between 90 W ThuVEP and 39.6 W HoLEP was the recatheterization rate and QoL at 4-week follow-up, which were, however, within the range given in the literature [4, 5]. As a last limitation, a clear differentiation of the ThuVEP technique from the ThuLEP technique is difficult to define, since there are smooth transitions from each technique: ThuLEP is a blunt enucleation technique with Tm:YAG laser support using the beak of the resectoscope for dissecting off the adenoma from the pseudocapsule of the prostate, while the Tm:YAG laser is continuously applied to the layer of enucleation for dissecting off the prostate from the surgical pseudocapsule in ThuVEP [30].

Conclusions

ThuVEP and HoLEP are both safe and effective procedures for the treatment of symptomatic BPO in enlarged prostates. Both procedures give equivalent and satisfactory micturition improvement with low morbidity at 1-month follow-up.