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Holmium Laser Enucleation of the Prostate Versus Open Prostatectomy for Prostates >70 g: 24-Month Follow-up
european urology 50 (2006) 563–568
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Benign Prostatic Obstruction
Holmium Laser Enucleation of the Prostate Versus Open Prostatectomy for Prostates >70 g: 24-Month Follow-up Richard Naspro *, Nazareno Suardi, Andrea Salonia, Vincenzo Scattoni, Giorgio Guazzoni, Renzo Colombo, Andrea Cestari, Alberto Briganti, Bruno Mazzoccoli, Patrizio Rigatti, Francesco Montorsi Department of Urology, University ‘‘Vita-Salute’’, Scientific Institute H. San Raffaele, Milan, Italy
Article info
Abstract
Article history: Accepted April 11, 2006 Published online ahead of print on May 2, 2006
Objective: Prospectively evaluate perioperative outcomes and 2-yr follow-up after holmium laser enucleation (HoLEP) and standard open prostatectomy (OP) for treating benign prostatic hyperplasia-related obstructed voiding symptoms, with prostates >70 g. Methods: From March 2003 to December 2004, 80 consecutive patients were randomised for surgical treatment with HoLEP (n = 41) or standard OP (n = 39). All patients were preoperatively assessed with International Prostate Symptom Score and International Index of Erectile Function questionnaires and complete urodynamic evaluation. Intraoperative and perioperative parameters such as blood loss, catheter removal, and hospital stays were assessed. Early and late complications were recorded. Patients were evaluated at 1-, 3-, 12-, and 24-mo follow-ups with the same tests. Results: Operating room time was significantly shorter for the OP group (72.09 21.22 min vs. 58.31 11.95 min, p < 0.0001); catheter removal (1.5 1.07 d and 4.1 0.5 d, p < 0.001) and hospital stay (2.7 1.1 d vs. 5.4 1.05 d, p < 0.001) were shorter in the HoLEP group. Blood loss was less and blood transfusions fewer in the HoLEP group ( p < 0.001). In both groups urodynamic and uroflowmetry findings improved from baseline, were still evident at the 24-mo follow-up, and were comparable between the two groups. Late complications were also comparable. Conclusions: HoLEP is a feasible technique for treating large prostates. Functional results are similar to OP at the 2-yr follow-up. Reduced catheterisation, hospital stay, and blood loss make HoLEP an attractive option for the treatment of large prostates.
Keywords: Benign prostatic hyperplasia Holmium Laser surgery Open prostatectomy
# 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Department of Urology, Universita` ‘‘Vita-Salute’’, Istituto Scientifico H. San Raffaele, Via Olgettina 60, 20132 Milano, Italy. Tel. +39 02 26437286; Fax: +39 02 26437298. E-mail address: [email protected] (R. Naspro). 0302-2838/$ – see back matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2006.04.003
564
1.
european urology 50 (2006) 563–568
Introduction
Open prostatectomy (OP) is the most common surgical approach for benign prostate hyperplasia (BPH) in large prostates in many parts of Europe [1,2]. 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 [4–6]. 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 80–200 g and had encouraging results in terms of short hospital stay and catheterisation time with low perioperative morbidity [7–10]. 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 >100 g 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 >70 g. 2.
Patients and methods
From March 2003 to December 2004, 80 consecutive patients who suffered from BPH-related obstructed voiding symptoms with prostate volume >70 g, 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 <150 ml, peak urinary flow rate <15 ml/s, and urodynamic obstruction (Scha¨fer 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 >4.0 ng/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 followup 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 Table 1 – Patient characteristics
No. of patients Mean age, yr Total serum PSA, ng/ml TRUS volume, g Adenoma volume, g Incidental adenocarcinoma
HoLEP
OP
p value
41 66.26 6.55 6.33 3.45
39 67.27 6.72 6.99 4.28
p = 0.56 p = 0.49
113.27 35.33 89.40 32.82 2 (4.8%)
124.21 38.52 93.39 30.64 3 (7.6%)
p = 0.23 p = 0.61 p = 0.02
Data are mean standard deviation of the mean. HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy.
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european urology 50 (2006) 563–568
Table 2 – Perioperative data
Total operative time, min Specimen weight, g Hb levels drop, g/dl Autologous blood transfusion Homologous blood transfusion Catheterisation time, d Hospital stay, d
Table 4 – Urodynamic findings
HoLEP
OP
p value
72.09 21.22
58.31 11.95
p < 0.0001
59.33 34.77 2.12 1.48 2 (4%)
87.90 41.11 3.15 1.33 5 (12.8%)
p = 0.0046 p = 0.0073 p < 0.001
0
2 (5.1%)
p < 0.007
1.5 1.07
4.1 0.5
p < 0.0001
2.7 1.1
5.43 1.05
p < 0.0001
Data shown as mean standard deviation of the mean. HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy.
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
Baseline
12 mo
Mean detrusor pressure at maximum flow rate (Pdet,qmax) cm H2O HoLEP group 80.6 (44–130) 30.6 (22–80) OP group 83.1 (41–147) 34.8 (18–88) p value p = 0.94 p = 0.66 Scha¨fer grade (LinPURR) HoLEP group 3.8 (2–6) OP group 3.1 (2–6) p value p = 0.33
0.7 (0–4) 0.8 (0–4) p = 0.18
p value
<0.001 <0.001
<0.001 <0.001
HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy; LinPURR = linear passive urethral resistance relation.
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).
Table 3 – Follow-up data Baseline
1 mo
3 mo
12 mo
24 mo
Qmax HoLEP group OP group p value
7.83 3.42 8.32 2.37 0.64
26.6 8.7 24.3 6.8 0.53
22.2 8.6 25.5 10.5 0.57
22.32 3.8 24.21 6.49 0.27
19.19 6.3 20.11 8.8 0.91
Qave HoLEP group OP group p value
5.28 2.78 4.76 1.63 0.59
12.2 4.3 11.1 3.1 0.77
14.4 7.1 10.1 6.6 0.01
12.2 4.2 14.1 3.7 0.18
11.6 5.3 12.2 5.3 0.88
IPSS HoLEP group OP group p value
20.11 5.84 21.60 3.24 0.27
6.9 4.2 4.7 2.1 0.20
3.9 2.9 2.9 2.6 0.46
8.45 5.87 8.40 6.0 0.98
7.9 6.2 8.1 7.1 0.44
QOL question HoLEP group OP group p value
4.07 0.93 4.44 0.96 0.17
1.4 1.4 1.3 0.7 0.76
1 0.8 0.6 0.2 0.18
1.7 0.94 1.77 0.83 0.85
1.5 0.87 1.66 0.76 0.76
Qmax = ; HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy; Qave = ; IPSS = International Prostate Symptom Score; QOL = quality of life.
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european urology 50 (2006) 563–568
Table 5 – Perioperative morbidity HoLEP (n = 41) Early postoperative complications, from surgery to 3-mo follow-up Bladder mucosal injury 3 (7.3%) Transitory urge incontinence 14 (34.1%) Dysuria (burning) 28 (68.2%) Stress incontinence 1 (2.4%) Reintervention for bleeding 1 (2.4%) Early acute urinary retention 5 (12.1%) 12-mo follow-up complications Urge incontinence Dysuria (burning) Bladder-neck/urethral strictures Overall reintervention Prostate cancer
2 4 2 2 4
24-mo follow-up complications Prostate cancer Dysuria (burning) Bladder-neck/urethral strictures
0 1 (2.8%) 1 (2.8%)
OP (n = 39) 0 17 16 1 0 2
(5.4%) (10.8%) (5.4%) (5.4%) (10.8%)
3 3 2 2 4
(5.1%)
p < 0.001 p = 0.2 p < 0.001 p = 0.9 p = 0.9 p = 0.11
(8.5%) (8.5%) (5.7%) (5.7%) (11.4%)
p = 0.03 p = 0.02 p = 0.3 p = 0.55 p = 0.4
(38.6%) (41.0%) (2.5%)
0 1 (3.3%) 1 (3.3%)
p = 0.02 p = 0.3
HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy.
Table 6 – IIEF-5 scores: HoLEP versus OP
IIEF IIEF IIEF IIEF IIEF
domains domains domains domains domains
baseline 3 mo 6 mo 12 mo 24 mo
HoLEP
OP
p value
20.3 6.6 21.4 2.6 22.8 2.1 25.2 4.2 22.3 4.0
21.1 5.3 20.6 5.5 24.6 4.0 23.5 1.8 21.9 5.6
p = 0.5 p = 0.67 p = 0.55 p = 0.31 p = 0.21
Data are mean standard deviation of the mean. IEFF = International Index of Erectile Function; HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy.
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 1yr 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 [5–7]. Many authors have described the feasibility and safety of the procedure in patients with larger prostates, especially since the introduction of the morcellator [4–9,15]. 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 >100 g 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
european urology 50 (2006) 563–568
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 followup. 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 >70 g 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
567
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.
References [1] Jepsen JV, Bruskewitz RC. Recent developments in the surgical management of benign prostatic hyperplasia. Urology 1998;51:23–31. [2] Varkarakis I, Kyriakakis Z, Delis A, Protogerou V, Deliveliotis C. Long-term results of open transvesical prostatectomy from a contemporary series of patients. Urology 2004;64:306–10. [3] Keoghane SR, Lawrence KC, Gray AM, et al. A double blind randomized controlled trial and economic evaluation of transurethral resection vs contact laser vaporization for benign prostatic enlargement: a 3 year follow-up. BJU Int 2000;85:74–8. [4] Tan AH, Gilling PJ, Kennett KM, Frampton C, Westenberg AM, Fraundorfer MR. A randomized trial comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200 grams). J Urol 2003;170: 1270–4.
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[5] Kuntz RM, Ahyai S, Lehrich K, Fayad A. Transurethral holmium laser enucleation of the prostate versus transurethral electrocautery resection of the prostate: a randomized prospective trial in 200 patients. J Urol 2004;172:1012–6. [6] Montorsi F, Naspro R, Salonia A, et al. Holmium laser enucleation versus trans-urethral resection of the prostate: results from a two-centre prospective randomized trial in patients with obstructive benign prostatic hyperplasia. J Urol 2004;172:1926–9. [7] Gilling PJ, Kennett KM, Fraundorfer MR. Holmium laser enucleation of the prostate for glands larger than 100 gr: an endourologic alternative to open prostatectomy. J Endourol 2000;14:529–31. [8] Hurle R, Vavassori I, Piccinelli A, Manzetti A, Valenti S, Vismara A. Holmium laser enucleation of the prostate combined with mechanical morcellation in 155 patients with benign prostatic hyperplasia. Urology 2002;60: 449–53. [9] Kuntz RM, Lehrich K. Holmium laser enucleation versus open enucleation for large prostates. J Urol 2002;168: 1465–8. [10] Elzayat EA, Elhilali MM. Holmium laser enucleation of the prostate (HoLEP): the endourologic alternative to open prostatectomy. Eur Urol 2006;49:87–91. [11] McConnell JD, Barry MJ, Bruskewitz RC, et al. Clinical practice guideline: benign prostatic hyperplasia: diagnosis and treatment. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, publication no. 94-0582, 1994. [12] Kuntz RM, Lehrich K, Ahyai S. Transurethral holmium laser enucleation of the prostate compared with transvesical open prostatectomy: 18-month follow-up of a randomized trial. J Endourol 2004;18:189–91. [13] Gilling PJ, Kennett K, Das AK, Thompson D, Fraundorfer MR. Holmium laser enucleation of the prostate (HoLEP) combined with transurethral tissue morcellation: an update on the early clinical experience. J Endourol 1998;12:457–9. [14] Witherington R, Shelor Jr WC. Suprapubic prostatectomy. Modified Hryntschak technique. Urology 1974;4:550–6.
[15] Moody JA, Lingeman JE. Holmium laser enucleation for prostate adenoma greater than 100 gm: comparison to open prostatectomy. J Urol 2001;165:459–62. [16] Serretta V, Morgia G, Fondacaro L, et al., Members of the Sicilian-Calabrian Society of Urology. Open prostatectomy for benign prostatic enlargement in southern Europe in the late 1990s: a contemporary series of 1800 interventions. Urology 2002;60:623–7. [17] Kuntz RM, Lehrich K, Ahyai S. Does perioperative outcome of transurethral holmium laser enucleation of the prostate depend on prostate size? J Endourol 2004;18: 183–8. [18] Elzayat EA, Habib EI, Elhilali MM. Holmium laser enucleation of the prostate: a size-independent new ‘‘gold standard’’. Urology 2005;66:108–13. [19] Millin T. Retropubic prostatectomy: a new extravesical technique report on 20 cases. 1945. J Urol 2002;167:976–9. [20] Naspro R, Freschi M, Salonia A, et al. Holmium laser enucleation (HoLEP) versus trans-urethral resection (TURP) of the prostate: are histological findings comparable? J Urol 2004;171:1203–6. [21] El-Hakim A, Elhilali MM. Holmium laser enucleation of the prostate can be taught: the first learning experience. BJU Int 2002;90:863. [22] Seki N, Mochida O, Kinukawa N, Sagiyama K, Naito S. Holmium laser enucleation for prostatic adenoma: analysis of learning curve over the course of 70 consecutive cases. J Urol 2003;170:1847–50. [23] Peterson MD. Holmium laser enucleation of the prostate for men with urinary retention. J Urol 2005;174:998–1001. [24] Tooher R, Sutherland P, Costello A, Gilling P, Rees G, Maddern G. A systematic review of holmium laser prostatectomy for benign prostatic hyperplasia. J Urol 2004;171:1773–81. [25] Fraundorfer MR, Gilling PJ, Kennett KM, Dunton NG. Holmium laser resection of the prostate is more cost effective than transurethral resection of the prostate: results of a randomized prospective study. Urology 2001;57:454–8. [26] Salonia A, et al. Holmium laser enucleation versus open prostatectomy for benign prostatic hyperplasia: an inpatient cost analysis. Urology. In press.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Benign Prostatic Obstruction
Holmium Laser Enucleation of the Prostate Versus Open Prostatectomy for Prostates >70 g: 24-Month Follow-up Richard Naspro *, Nazareno Suardi, Andrea Salonia, Vincenzo Scattoni, Giorgio Guazzoni, Renzo Colombo, Andrea Cestari, Alberto Briganti, Bruno Mazzoccoli, Patrizio Rigatti, Francesco Montorsi Department of Urology, University ‘‘Vita-Salute’’, Scientific Institute H. San Raffaele, Milan, Italy
Article info
Abstract
Article history: Accepted April 11, 2006 Published online ahead of print on May 2, 2006
Objective: Prospectively evaluate perioperative outcomes and 2-yr follow-up after holmium laser enucleation (HoLEP) and standard open prostatectomy (OP) for treating benign prostatic hyperplasia-related obstructed voiding symptoms, with prostates >70 g. Methods: From March 2003 to December 2004, 80 consecutive patients were randomised for surgical treatment with HoLEP (n = 41) or standard OP (n = 39). All patients were preoperatively assessed with International Prostate Symptom Score and International Index of Erectile Function questionnaires and complete urodynamic evaluation. Intraoperative and perioperative parameters such as blood loss, catheter removal, and hospital stays were assessed. Early and late complications were recorded. Patients were evaluated at 1-, 3-, 12-, and 24-mo follow-ups with the same tests. Results: Operating room time was significantly shorter for the OP group (72.09 21.22 min vs. 58.31 11.95 min, p < 0.0001); catheter removal (1.5 1.07 d and 4.1 0.5 d, p < 0.001) and hospital stay (2.7 1.1 d vs. 5.4 1.05 d, p < 0.001) were shorter in the HoLEP group. Blood loss was less and blood transfusions fewer in the HoLEP group ( p < 0.001). In both groups urodynamic and uroflowmetry findings improved from baseline, were still evident at the 24-mo follow-up, and were comparable between the two groups. Late complications were also comparable. Conclusions: HoLEP is a feasible technique for treating large prostates. Functional results are similar to OP at the 2-yr follow-up. Reduced catheterisation, hospital stay, and blood loss make HoLEP an attractive option for the treatment of large prostates.
Keywords: Benign prostatic hyperplasia Holmium Laser surgery Open prostatectomy
# 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Department of Urology, Universita` ‘‘Vita-Salute’’, Istituto Scientifico H. San Raffaele, Via Olgettina 60, 20132 Milano, Italy. Tel. +39 02 26437286; Fax: +39 02 26437298. E-mail address: [email protected] (R. Naspro). 0302-2838/$ – see back matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2006.04.003
564
1.
european urology 50 (2006) 563–568
Introduction
Open prostatectomy (OP) is the most common surgical approach for benign prostate hyperplasia (BPH) in large prostates in many parts of Europe [1,2]. 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 [4–6]. 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 80–200 g and had encouraging results in terms of short hospital stay and catheterisation time with low perioperative morbidity [7–10]. 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 >100 g 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 >70 g. 2.
Patients and methods
From March 2003 to December 2004, 80 consecutive patients who suffered from BPH-related obstructed voiding symptoms with prostate volume >70 g, 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 <150 ml, peak urinary flow rate <15 ml/s, and urodynamic obstruction (Scha¨fer 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 >4.0 ng/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 followup 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 Table 1 – Patient characteristics
No. of patients Mean age, yr Total serum PSA, ng/ml TRUS volume, g Adenoma volume, g Incidental adenocarcinoma
HoLEP
OP
p value
41 66.26 6.55 6.33 3.45
39 67.27 6.72 6.99 4.28
p = 0.56 p = 0.49
113.27 35.33 89.40 32.82 2 (4.8%)
124.21 38.52 93.39 30.64 3 (7.6%)
p = 0.23 p = 0.61 p = 0.02
Data are mean standard deviation of the mean. HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy.
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Table 2 – Perioperative data
Total operative time, min Specimen weight, g Hb levels drop, g/dl Autologous blood transfusion Homologous blood transfusion Catheterisation time, d Hospital stay, d
Table 4 – Urodynamic findings
HoLEP
OP
p value
72.09 21.22
58.31 11.95
p < 0.0001
59.33 34.77 2.12 1.48 2 (4%)
87.90 41.11 3.15 1.33 5 (12.8%)
p = 0.0046 p = 0.0073 p < 0.001
0
2 (5.1%)
p < 0.007
1.5 1.07
4.1 0.5
p < 0.0001
2.7 1.1
5.43 1.05
p < 0.0001
Data shown as mean standard deviation of the mean. HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy.
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
Baseline
12 mo
Mean detrusor pressure at maximum flow rate (Pdet,qmax) cm H2O HoLEP group 80.6 (44–130) 30.6 (22–80) OP group 83.1 (41–147) 34.8 (18–88) p value p = 0.94 p = 0.66 Scha¨fer grade (LinPURR) HoLEP group 3.8 (2–6) OP group 3.1 (2–6) p value p = 0.33
0.7 (0–4) 0.8 (0–4) p = 0.18
p value
<0.001 <0.001
<0.001 <0.001
HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy; LinPURR = linear passive urethral resistance relation.
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).
Table 3 – Follow-up data Baseline
1 mo
3 mo
12 mo
24 mo
Qmax HoLEP group OP group p value
7.83 3.42 8.32 2.37 0.64
26.6 8.7 24.3 6.8 0.53
22.2 8.6 25.5 10.5 0.57
22.32 3.8 24.21 6.49 0.27
19.19 6.3 20.11 8.8 0.91
Qave HoLEP group OP group p value
5.28 2.78 4.76 1.63 0.59
12.2 4.3 11.1 3.1 0.77
14.4 7.1 10.1 6.6 0.01
12.2 4.2 14.1 3.7 0.18
11.6 5.3 12.2 5.3 0.88
IPSS HoLEP group OP group p value
20.11 5.84 21.60 3.24 0.27
6.9 4.2 4.7 2.1 0.20
3.9 2.9 2.9 2.6 0.46
8.45 5.87 8.40 6.0 0.98
7.9 6.2 8.1 7.1 0.44
QOL question HoLEP group OP group p value
4.07 0.93 4.44 0.96 0.17
1.4 1.4 1.3 0.7 0.76
1 0.8 0.6 0.2 0.18
1.7 0.94 1.77 0.83 0.85
1.5 0.87 1.66 0.76 0.76
Qmax = ; HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy; Qave = ; IPSS = International Prostate Symptom Score; QOL = quality of life.
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Table 5 – Perioperative morbidity HoLEP (n = 41) Early postoperative complications, from surgery to 3-mo follow-up Bladder mucosal injury 3 (7.3%) Transitory urge incontinence 14 (34.1%) Dysuria (burning) 28 (68.2%) Stress incontinence 1 (2.4%) Reintervention for bleeding 1 (2.4%) Early acute urinary retention 5 (12.1%) 12-mo follow-up complications Urge incontinence Dysuria (burning) Bladder-neck/urethral strictures Overall reintervention Prostate cancer
2 4 2 2 4
24-mo follow-up complications Prostate cancer Dysuria (burning) Bladder-neck/urethral strictures
0 1 (2.8%) 1 (2.8%)
OP (n = 39) 0 17 16 1 0 2
(5.4%) (10.8%) (5.4%) (5.4%) (10.8%)
3 3 2 2 4
(5.1%)
p < 0.001 p = 0.2 p < 0.001 p = 0.9 p = 0.9 p = 0.11
(8.5%) (8.5%) (5.7%) (5.7%) (11.4%)
p = 0.03 p = 0.02 p = 0.3 p = 0.55 p = 0.4
(38.6%) (41.0%) (2.5%)
0 1 (3.3%) 1 (3.3%)
p = 0.02 p = 0.3
HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy.
Table 6 – IIEF-5 scores: HoLEP versus OP
IIEF IIEF IIEF IIEF IIEF
domains domains domains domains domains
baseline 3 mo 6 mo 12 mo 24 mo
HoLEP
OP
p value
20.3 6.6 21.4 2.6 22.8 2.1 25.2 4.2 22.3 4.0
21.1 5.3 20.6 5.5 24.6 4.0 23.5 1.8 21.9 5.6
p = 0.5 p = 0.67 p = 0.55 p = 0.31 p = 0.21
Data are mean standard deviation of the mean. IEFF = International Index of Erectile Function; HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy.
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 1yr 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 [5–7]. Many authors have described the feasibility and safety of the procedure in patients with larger prostates, especially since the introduction of the morcellator [4–9,15]. 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 >100 g 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
european urology 50 (2006) 563–568
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 followup. 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 >70 g 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
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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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