For the past 30 yr, the gold standard treatment for smaller prostates has been transurethral resection of the prostate (TURP) [3], but growing evidence suggests that holmium laser with prostate enucleation (HoLEP) can be an effective and safe alternative with overall functional results similar to standard TURP in terms of relief of subjective symptoms and urodynamic findings [4], [5], [6].

The good results achieved with relatively small prostates have also been confirmed with larger glands. In a series of studies, HoLEP was demonstrated to be safe and effective for the treatment of prostates 80–200g and had encouraging results in terms of short hospital stay and catheterisation time with low perioperative morbidity [7], [8], [9], [10].

Despite the overall good long-term results and the low reoperation rates after OP, the high perioperative morbidity associated with this approach stresses the need to find an adequate alternative that can reproduce the same functional results and drastically reduce morbidity [11]. However, to our knowledge only one prospective randomised study compares OP with HoLEP for prostates >100g with a minimum follow-up period of 18 mo [12].

Our paper describes the perioperative findings and 2-yr follow-up results that compare HoLEP and OP for the treatment of patients with urodynamically obstructed BPH with prostates >70g.

2. Patients and methods

From March 2003 to December 2004, 80 consecutive patients who suffered from BPH-related obstructed voiding symptoms with prostate volume >70g, as determined by transrectal ultrasound (TRUS), and who had not responded to pharmacologic therapy were considered eligible for surgical treatment and enrolled in this randomised prospective study. The following inclusion criteria were considered: postvoiding residue <150ml, peak urinary flow rate <15ml/s, and urodynamic obstruction (Schäfer grade>2). Exclusion criteria were neurogenic bladder, history of adenocarcinoma of the prostate, or any previous prostatic, bladder-neck, or urethral surgery. At baseline, no patients had an indwelling catheter. The patients were randomised with a computer-generated table to be treated surgically either with HoLEP (group 1, n=41) or standard OP (group 2, n=39).

The surgical technique used for the HoLEP was previously described by Gilling et al. [13] and included enucleation of the prostatic lobes with subsequent tissue morcellation into the fragments, which were retrieved from the bladder cavity. The standard transvesicle approach was used to perform OP [14]. All procedures in both groups were performed by two senior staff urologists. All patients were assessed preoperatively by physical examination, including digital rectal examination (DRE), total and free serum prostate-specific antigen (PSA) levels, postvoid residual urine volume measurement, uroflowmetry and pressure-flow study, kidney-bladder and TRUS, and by scoring of subjective symptoms with the International Prostate Symptom Score (IPSS) and Quality of Life (QOL) questionnaires. For the investigational aim of the study all patients banked 1 IU autologous blood. TRUS-guided prostate biopsy, abnormal DRE, and total serum PSA levels >4.0ng/dl were used to exclude suspected prostate cancer. Sexual function was assessed by means of the International Index of Erectile Function (IIEF-5).

Recorded intraoperative data included total time in the operating room, the quantity (in grams) of tissue removed and, for the HoLEP group only, time of enucleation and morcellation (in minutes). The retrieved tissue specimens were weighed and examined histologically. Recorded perioperative parameters included postoperative drop in serum haemoglobin levels, catheterisation time, length of hospital stay, and histologic diagnosis. Any transfusion was initiated when haemodynamically indicated or when the venous haemoglobin concentration decreased significantly (i.e., drop>20%) according to the protocol established by our anaesthesiologists.

Patients were evaluated at the 1-, 3-, 12-, and 24-mo follow-up dates with preoperative questionnaires and diagnostic tests. Complete urodynamic evaluation was performed at the 12-mo follow-up only for this study.

All data were statistically analysed with the Student t test and are presented as mean±standard deviation of the mean (SD). A two-tailed Student t test for impaired data was used to compare data obtained from the two groups. For all statistical comparisons, significance was defined with p<0.05. The study was approved by our ethics committee and all patients signed an informed consent.

3. Results

The main characteristics of the patients are shown in Table 1. Time in the operating room was significantly longer for the HoLEP group; catheter removal and hospital stay were significantly shorter in the HoLEP group than in the OP group. Table 2 lists perioperative results from both groups. Blood loss was less (p=0.0073) and blood transfusions were fewer in the HoLEP group both in terms of autologous (p<0.001) and homologous (p<0.007) transfusions. Only one patient from the HoLEP group underwent early endoscopic reintervention for bleeding. Thirty-five and 30 patients, respectively, were eligible for 24-mo follow-up in each group. Functional follow-up data are reported in Table 3; the urodynamic findings are summarised in Table 4. In both groups urodynamic and uroflowmetry data showed an improvement in obstruction relief, starting with the 3-mo follow-up and reaching a plateau at the 24-mo follow-up. In terms of postoperative irritative symptoms, at the 3-month follow-up the most common finding in both groups was a certain degree of dysuria, which is defined as burning associated with frequency, more frequent in the HoLEP group (68.2%) compared to the OP (41.0%) group (p<0.001). Stress incontinence was reported in one patient in each group (Table 5)..

All patients with irritative symptoms received medical therapy with significant progressive improvement that was recorded at the 6-mo follow-up. However, dysuria was still described by four (10.8%) and three (8.5%) patients at the 1-yr follow-up (p=0.02) and by one patient in both groups at the 2-yr follow-up. Erectile function, which was measured with the erectile function domain of the IIEF, showed no significant reduction in the follow-up period from baseline in either group (Table 6).

Diagnosis of incidental adenocarcinoma of the prostate was comparable in the two groups (two cases in the HoLEP and group and three cases in the OP group). Four patients in each group had a subsequent diagnosis of prostate cancer at the 1-yr follow-up; prostatic biopsy was performed because of rises in PSA levels. All 13 patients underwent radical prostatectomy. Five cases (12%) of early acute urinary retention were recorded in the HoLEP group compared to two (5%) in the OP group (p=0.11) and were all managed with subsequent temporary recatheterisation. Bladder-neck and urethral strictures were comparable in both groups at the 1- and 2-yr follow-up examinations. For three patients treatment consisted of internal urethrotomy; three had bladder-neck incisions (Table 5).

4. Discussion

HoLEP with morcellation has gained increasing credibility as a therapeutic option for bladder outlet obstruction (BOO) caused by symptomatic BPH and has been demonstrated to be at least as reliable and efficacious as TURP for small- to medium-sized prostates [5], [6], [7]. Many authors have described the feasibility and safety of the procedure in patients with larger prostates, especially since the introduction of the morcellator [4], [5], [6], [7], [8], [9], [15]. These results have launched this technique in the treatment of BPH in high-volume prostates as an alternative to standard TURP and OP, the traditional approaches to large prostates [15]. From a technical viewpoint, the HoLEP technique mimics OP in terms of identifying the plane between the adenoma and the prostatic capsule and mechanical enucleation of the adenoma on the prostatic capsule. Although OP-related mortality has definitively decreased in the latest reports and long-term results are consistent, perioperative morbidity is still high [2], [16]. The advantages of the HoLEP procedure are a nearly bloodless field due to the ability to efficiently coagulate even large bleeders, with the typical benefits of a minimally invasive and endoscopic approach such as lower blood loss, reduced perioperative morbidity, and shorter catheterisation and hospital stay.

To date, only one randomised controlled trial that compares HoLEP and OP with the transvesical approach is available in the literature [5]. In this study Kuntz and Lehrich compared HoLEP and OP for the treatment of prostates >100g and demonstrated the superiority of HoLEP in terms of reduced blood loss, catheterisation, and hospital stay with equivalent results at the 18-mo follow-up [12]. Furthermore, the safety of the HoLEP procedure was analysed according to prostate size. No difference was found in postoperative morbidity and clinical outcome between prostates of different sizes [17], [18].

Our current study confirms the overall safety of HoLEP and the clinical equivalence of the procedure with OP in terms of BOO relief with significantly reduced perioperative morbidity. The transfusion rates found in our OP series (17.9%) are higher than those generally reported in the literature (6.8–13.3%) [5], [16], and although most of the transfusions were with autologous blood, this confirms the elevated morbidity of the procedure. Therefore, many authors prefer the Millin extracapsular approach to the transvesical one because it better controls the bleeding [19]. A certain degree of subjective burning and urge incontinence were recorded frequently after HoLEP, but this was always a short-term and self-limiting condition and was probably caused by the high energy applied to the capsule during the procedure. Surprisingly, this finding did not differ as expected from the OP group, where many patients reported urge incontinence up to the 3-mo follow-up. We attributed this finding to a more thorough evaluation of patients in the protocol compared to patients who undergo OP routinely at our institution. Furthermore, patients with large prostates do not necessarily undergo preoperative and postoperative urodynamic assessment and rarely fill out subjective symptoms questionnaires, so their symptoms are easily underestimated.

For complications, results were comparable to those found in the literature for both procedures in both groups, where bladder-neck contractures and urethral strictures were the main causes of reoperation at the 1-yr follow-up. However, longer follow-up is necessary to assess the real impact of these procedures on maintenance of the promising medium-term functional results [2]. Pathologic diagnosis was similar in both groups; in particular, no differences in terms of cancer and detection of high-grade intraepithelial neoplasia (HGPIN) were registered. These data confirm recent findings in a comparison between HoLEP and TURP specimens [20]. Our study was specifically designed for prostates >70g and was undertaken after the learning curve was complete (after >200 cases). Some authors consider a learning curve to consist of >30 cases [21]. This number is probably sufficient to perform HoLEP safely, but, with challenging large prostates, experience certainly plays an important role [22].

Recently, Peterson demonstrated the safety and reliability of the procedure for treating BPH-related urinary retention in men with large prostates [23]. This paper contributes to the increasing data that confirm the HoLEP technique is ideal for large prostates because it is a safe and reliable alternative to OP and reduces the impact of perioperative morbidity. However, a review of the literature shows that long-term quality data are still lacking and mandatory before the HoLEP procedure can become a standardised alternative for TURP and OP [24]. Fraundorfer et al. demonstrated that HoLEP was more cost effective than TURP at 1-yr follow-up, considering perioperative data and the complication rate with the subsequent unplanned clinic visits and readmissions [25]. However, no data are available for the comparison of HoLEP and OP. In a specifically designed cost analysis performed at our department, HoLEP showed a significant reduction in blood loss compared to the OP group. Thus, it has a significantly shorter catheterisation time and hospital stay, with a significantly greater cost reduction for this procedure than OP [26]. However, such good results need to be confirmed in larger, multicentric, and randomised studies before HoLEP can become the standard technique for large prostates.

5. Conclusions

HoLEP is a safe and minimally invasive technique for the treatment of small and large prostates. Even though HoLEP takes longer to perform than OP, it is associated with reduced perioperative morbidity, significantly shorter catheterisation, and a shorter hospital stay. Furthermore, functional results are comparable at the 2-yr follow-up; thus, HoLEP is an attractive alternative to OP.

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