Accepted Article
Received Date : 11-Dec-2014 Revised Date : 05-Mar-2015 Accepted Date : 11-Mar-2015 Article type
: Original Article
Multicenter prospective evaluation of the learning curve of the holmium laser enucleation of the prostate (HoLEP)
Grégoire Roberta, Jean-Nicolas Cornub, Marc Fourmarierc, Christian Saussined, Aurélien Descazeaude, Abdel Rahmène Azzouzif, Eric Vicautg, Bertrand Lukacsb.
Affiliations a
Service d’urologie, université Bordeaux Segalen, CHU de Bordeaux, 2, Victor-Segalen, 33076, Bordeaux cedex, France b
Service d’urologie, Hôpital Tenon, Université Paris-6, Assistance publique—Hôpitaux de Paris, 75020 Paris, France c
Service d’urologie, centre hospitalier Aix-en-Provence, 13616 Aix-en-Provence, France
d
Service d’urologie, NHC, 1 place de l’hôpital, 67091 Strasbourg, France
e
Service de chirurgie urologique, hôpital Dupuytren, CHU de Limoges, 2, avenue
Martin-Luther-King, 87042 Limoges, France f
Service d’urologie, CHU d’Angers, 49933 Angers, France
g
Clinical Research Unit, Lariboisière-Fernand Widal Hospital, Assistance publique Hopitaux de Paris; University Paris Diderot, Paris, France
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bju.13124 This article is protected by copyright. All rights reserved.
Accepted Article
Corresponding Author: Bertrand Lukacs Department of Urology Tenon Hospital 4 rue de la Chine 75020 Paris, France Tel: +33156016495 Fax : +33156017306 Email: [email protected]
Keywords : prostate, enucleation, HoLEP, holmium, learning curve, prospective study.
Abstract Objectives: • To describe the step-by-step learning curve of Holmium Laser Enucleation (HoLEP) surgical technique. Patients and methods: • A prospective, multicentrer observational study was conducted, involving surgeons experienced in transurethral resection of the prostate and open prostatectomy, never having performed HoLEP were included. • The main judgment criterion was the ability of the surgeon to perform four consecutive successful procedures, defined by the following: complete enucleation and morcellation, within less than 90 minutes, without any conversion to standard
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TURP, with acceptable stress, and with acceptable difficulty (evaluated by Likert scales). Each surgeon included 20 consecutive cases. Results: • Of nine centers, three abandoned the procedure before the end of the study due to complications, and one was excluded for treating patients off protocol. • Only one centre achieved the main judgment criterion of four consecutive successful procedures. Overall, the procedures were successfully performed in 43.6% of cases. • Reasons for unsuccessful procedures were mainly operative time longer than 90 minutes (n=51), followed by conversion to TURP (n=14), incomplete morcellation (n=8), significant stress (n=9), or difficulty (n=14) during procedure. • Ignoring operating time , 64% of procedures were successful and four out of five centers did 4 consecutive successful cases. • Of the five centers who completed the study, four chose to continue HoLEP. Conclusion: • Even in a prospective training structure, HoLEP has a steep learning curve exceeding 20 cases, with almost half of our centres choosing to abandon or not to continue with the technique. Operating time and difficulty of the enucleation seem the most important problems for a beginner. A more intensely mentored and structured mentorship programme might allow safer adoption of the operation.
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Introduction Holmium laser enucleation of the prostate (HoLEP) was first described in 1995 (1), and is considered as a first line surgical option for transurethral relief of benign prostatic obstruction (BPO) (2). HoLEP has been shown in level 1 studies to have several advantages compared to transurethral resection of the prostate (TURP), including shorter hospital stay, reduced bleeding complications, absence of TURP-syndrome (3). Furthermore, functional outcomes of HoLEP have been stated to at least as good as after TURP, and comparable to those obtained with open prostatectomy (OP) for larger prostates (3, 4). HoLEP is thus often considered as a “new gold standard” by several authors (5, 6). However, in many centers, HoLEP has not yet replaced TURP and OP (7). HoLEP being seen as a more difficult and lengthy procedure, learning curve has been pointed out as a limitation for a high diffusion of this surgical technique now described 15 years ago (8-10). But to date, no study has been really focused on a detailed evaluation of the learning curve. Our goal was to describe the step-by-step learning curve of HoLEP surgical technique through a prospective, multicentrer observational study, based on pre-specified operative parameters.
Material and methods Study design. A prospective, multicentre clinical study was conducted in nine reference centres for LUTS/BPO management between March 2012 and July 2013. In each participating center, one surgeon was identified as being the local investigator. Participating
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surgeons had to fulfill the following criteria: willing to learn HoLEP technique, having no experience with HoLEP, having previous experience in TURP and OP. All surgeons had to complete an initiation training phase before beginning the trial. During this phase, all surgeons received a detailed course explaining the technique and a booklet describing the technical steps of the procedure. All centres were equipped with the Lumenis™ 100W laser generator and with a complete set of endoscopic instrumentation including the Piranha™ morcellator manufactured by Richard Wolf™. The surgeons received technical instructions from an expert and were mentored for the first 2 cases. No additional technical support was provided after the first two cases. The procedures were conducted as previously described (11, 12). Patients inclusion criteria. Patients were eligible to enter the study if aged of more than 50, showing an International Prostate Symptom Score (I-PSS) > 12, IPSS question 8> 3, maximum urinary flow rate (Qmax) under 12 ml/s, estimated prostate weight between 40 and 80 g and post-void residual volume of less than 300cc. Patients with any history of prostatic surgery, proven prostate cancer or ongoing anticoagulant therapy were excluded form the study. Pre-operative work-up included assessment of the following parameters: I-PSS symptom score, I-PSS bother score, DAN-PSSsex score, Global sexual satisfaction, quality of life score, urinary flow rate, postvoid residual volume, ultrasound examination of the prostate and PSA blood testing. All patients gave written informed consent to participate. Evaluation criteria. Main outcomes were based on operative parameters. The main judgment criterion was the ability of the surgeon to perform four consecutive successful procedures.
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The definition of a successful procedure (composite criterion) was a combination of complete enucleation and morcellation, within less than 90 minutes, without any conversion to standard TURP, with acceptable stress, and with acceptable difficulty. Stress and difficulty of the procedure were assessed by the surgeon himself, using a visual analogic scale and were considered acceptable if under 5/10.Time, stress and difficulty had to be evaluated for the five separated steps of the procedure: contact with the prostatic capsule, enucleation of the median lobe, enucleation of the lateral lobes, haemostasis, and morcellation. Secondary judgment criteria included operative parameters (laser data (duration, Joules number of fibers used, fibre type, morcellator and nephroscope type), tissue weight, irrigation volume, need for coagulation with another device, adverse events during the procedure, duration of the catheterization, post-operative irrigation (duration, volume, type), and hospital stay. A post-operative visit was scheduled at one, six and twelve month for evaluation of efficacy and delayed complications, but was not part of the current evaluation.
Statistical analyses Based on previously published studies evaluating the learning curve of the HoLEP procedure (8, 11, 13, 14), we decided to include 20 consecutive patients for each participating surgeon after the first two mentored cases. Descriptive analyses were conducted for all parameters. Results Nine surgeons from nine centers participated in this study. None of them had any previous experience with the HoLEP procedure. Four centers were excluded for the following reasons:
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one stopped after two patients without further explanation, one decided to give up after the first patient experienced severe stress urinary incontinence, one stopped the study because was not confident with the surgical technique, and another one treated patients by HoLEP outside the protocol during the study period, which was judged as a major protocol violation. Hence, five surgeons who treated 20 patients each were considered for the final analysis. The surgeons were aged 33 to 53 and had various experience with BPH surgery (2 of them had performed less than 50 TURP and less than 50 simple prostatectomies). Depending on the surgeon the inclusions lasted from 3 to 10 months from the first to the last patient. Two patients withdrew their consent before being operated. Patient characteristics are shown in table 1. Thirty-two patients had a urinary catheter before surgery due to urinary retention. Sixty-five patients had history of any cardiovascular disease, but no patient was receiving anti-coagulant or platelet aggregation inhibitors before surgery. A single surgeon achieved the main judgement criterion of four consecutive successful procedures. The total number of consecutive successful procedures was 6 for one surgeon, 3 for 3 surgeons and 1 for 1 surgeon. The total number of successful procedures ranged from 3 to 12 depending on the surgeon. Overall, the procedures were successfully performed in 43.6% of cases. Reasons for unsuccessful procedures were: operative time longer than 90 minutes (n=51), conversion to TURP (n=14), incomplete morcellation (n=8), significant stress (n=9), or difficulty (n=14) during procedure. In 21 cases, there were two reasons or more for failure. Operative parameters (main outcomes) are detailed in table 2 and 3. The mean duration of the This article is protected by copyright. All rights reserved.
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complete procedure was 106.5 minutes. Conversion to TURP was necessary in 14 cases either for coagulation (2 cases), resection of remaining tissue (10 cases) or for both reasons (1 case). In one additional case the laser device failed during the procedure, needing interruption of the laser enucleation and conversion to TURP (this case was included as a failure, possibly impacting the results of the consecutive cases in this specific center). Conversion to TURP occurred in four different centres.
Peri-operative data are displayed in table 4. The mean post-operative duration of haematuria was 67.4±111.2 hours. Twenty-three patients encountered prolonged postoperative bleeding requiring maintenance of bladder irrigation and/or bladder clots removal during post-operative period. None of them had to be re-operated. Transfusion was necessary in one patient. Urinary tract infection was reported in 5 patients. All patients were discharged without urinary catheter.
Discussion With only one surgeon achieving to complete four consecutive successful procedures, our results confirmed that the HoLEP learning curve is at least of 20 procedures, underlying the difficulty for the surgeon to get confidence, and speed at the beginning of surgical experience. Such global results have already been stated by others in other studies. Shah et al evaluated the learning curve of an experienced endourologist (10). They prospectively collected data from the first 160 cases and concluded the enucleation and morcellation efficiency reached
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a plateau after 50 cases. Placer et al retrospectively analysed their results with 125 consecutive patients operated by a single surgeon (9). Once again, they found enucleation and morcellation efficiency rates improved significantly after the first 50 cases. Seki et al, in a retrospective evaluation, have shown that enucleation efficacy increased during the first 70 cases (15). However, none of these studies were designed to detail the learning curve and the steps limiting the ability of the surgeon to conduct successful procedures. In the present study, we focused the primary outcome of our prospective evaluation on the learning curve itself and were able to identify the parameters influencing successful outcomes. The main parameter that led to unsuccessful procedure as defined by the protocol was the operating time. Indeed, considering that an acceptable time to complete the whole procedure would be 120 minutes rather than 90 minutes, would lead to 61.7% success rate and to 4 different surgeons achieving to complete 4 consecutive successful procedures instead of one. The rather stringent criterion of 90 minutes was based on the experience gained with practice of TURP and upon advice of experts of HoLEP, but this cut-off might be not the best one at the beginning of surgical experience, when the surgeons are even not really familiar with the device. However, difficulty of the procedure was also perceived as a limitation, more than stress of the surgeon. According to the detailed, step by step evaluation, enucleation itself was seen as the most difficult part (table 3). According to the investigators’ experience, enucleation of the median lobe was always easier than lateral lobes, and as such, enucleation of solely the median lobe might be a useful option at the beginning of the learning curve.
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Laser failure occurred in one patient and might have impact the curve for one center, as this case was considered as a failure because converted to TURP). Once again, the stringent criteria of the study have to be considered when analysing the data. Despite these initial results, four of the five centers decided to continue to use HoLEP and increased their experience. The one who stopped did not continue to use the technique because the healthcare center was not able to get the laser equipment, but was keen to continue the technique. Hence, if 20 cases are probably not enough to overcome the learning curve (despite this cut-off has been proposed by some HoLEP users) 20 cases are probably sufficient to give the surgeon the willingness to continue with the technique. Furthermore, it does suggest that more closely supervised training programmes may help new users deliver efficiency and patient safety than more “traditional” approaches.
Our results emphasize the fact that HoLEP is quite difficult for beginners and has a steep learning curve. The participating surgeons did not receive any technical assistance after the first two cases did, and the present data indirectly confirm, although without a comparison group, that mentorship should be useful for optimization of the learning curve and prevent some drop outs, as already suggested by others (11, 12). Our detailed evaluation may be a useful tool to monitor the evolution of the surgeon’s performance during the learning period, as detailed technical steps have been recently reviewed but not subjected to separate, individualized evaluation. Our study has several limitations. First, not all the centres completed the study, but the exclusion of some centres gives in itself important information. For various reasons, 3 out of 10 surgeons, initially motivated to develop the technique have stopped the trial, that This article is protected by copyright. All rights reserved.
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highlight the fact that alone, without mentorship or motivated co-workers, a surgeon is at risk to abandon the technique and get back to previous gold standard. Then, our study was focused on operative parameters and it should be useful to assess the efficacy outcomes and complications, to see if they are impacted by the learning curve, as postulated by previous studies (15). Notably, detailed clinical data about cases treated by HoLEP in the four centers excluded were nt included in the present analysis, which should be seen as a drawback as the study is to be analysed in intent to treat. However, complications in these patients were limited to one severe case of urinary incontinence, as previously mentioned. Furthermore, the inclusion of patients with catheter in place pre-operatively may have influenced the results as these patients have usually more vascular glands. Another potential limitation is that 20 cases appears not enough to get out of the learning curve, and the inclusion of more patients in each centre may have been even more demonstrative.
Conclusion HoLEP learning curve is known to be steep; in our experience it exceeds 20 procedures for most of surgeons. Through a detailed, prospective evaluation of the different technical steps of the procedure, we were able to show that excessive operating time and difficulty of the enucleation itself are the most important limitation to overcome for a beginner. Such detailed evaluation could be useful in a structured mentorship programme.
Acknowledgements: This study was conducted based on a grant from the French Ministry of Health (STIC).
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The authors would like to thank Lumenis and EDAP-TMS for their technical assistance.
Links of interest: Christian Saussine receives consultancies from GSK and Lilly, and is investigator for AMS and EDAP-TMS. Marc Fourmarier is proctor for EDAP-TMS and speaker fro Lumenis. Jean-Nicolas Cornu has received research funding from Assistance Publique Hôpitaux de Paris, French Ministry of Health, Oak Ridge Associated Universities, the Association Française d'Urologie and GSK, and has received consultancies and travel grants from Bard, AMS, EDAPTMS, Coloplast, Pfizer, MundiPharma, Astellas, Bouchara-Recordati, Biocompatibples UK and Takeda, and is proctor for AMS.
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Gilling PJ, Cass CB, Malcolm AR, Fraundorfer MR. Combination holmium and Nd:YAG laser ablation of the prostate: initial clinical experience. Journal of endourology / Endourological Society. 1995;9(2):151-3.
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Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. European urology. 2013;64(1):118-40.
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Cornu JN, Ahyai S, Bachmann A, de la Rosette J, Gilling P, Gratzke C, et al. A Systematic Review and Meta-analysis of Functional Outcomes and Complications Following Transurethral Procedures for Lower Urinary Tract Symptoms Resulting from Benign Prostatic Obstruction: An Update. European urology. 2014.
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4.
Ahyai SA, Gilling P, Kaplan SA, Kuntz RM, Madersbacher S, Montorsi F, et al. Metaanalysis of functional outcomes and complications following transurethral procedures for lower urinary tract symptoms resulting from benign prostatic enlargement. European urology. 2010;58(3):384-97.
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Lingeman JE. Holmium laser enucleation of the prostate-if not now, when? The Journal of urology. 2011;186(5):1762-3.
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van Rij S, Gilling PJ. In 2013, holmium laser enucleation of the prostate (HoLEP) may be the new 'gold standard'. Current urology reports. 2012;13(6):427-32.
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Kim M, Lee HE, Oh SJ. Technical Aspects of Holmium Laser Enucleation of the Prostate for Benign Prostatic Hyperplasia. Korean journal of urology. 2013;54(9):5709.
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Elzayat EA, Elhilali MM. Holmium laser enucleation of the prostate (HoLEP): longterm results, reoperation rate, and possible impact of the learning curve. European urology. 2007;52(5):1465-71.
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Placer J, Gelabert-Mas A, Vallmanya F, Manresa JM, Menendez V, Cortadellas R, et al. Holmium laser enucleation of prostate: outcome and complications of self-taught learning curve. Urology. 2009;73(5):1042-8.
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Shah HN, Mahajan AP, Sodha HS, Hegde S, Mohile PD, Bansal MB. Prospective evaluation of the learning curve for holmium laser enucleation of the prostate. The Journal of urology. 2007;177(4):1468-74.
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Tan AH, Gilling PJ. Holmium laser prostatectomy: current techniques. Urology. 2002;60(1):152-6.
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El-Hakim A, Elhilali MM. Holmium laser enucleation of the prostate can be taught: the first learning experience. BJU international. 2002;90(9):863-9.
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Kuntz RM, Lehrich K. Transurethral holmium laser enucleation versus transvesical open enucleation for prostate adenoma greater than 100 gm.:: a randomized prospective trial of 120 patients. The Journal of urology. 2002;168(4 Pt 1):1465-9.
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14.
Moody JA, Lingeman JE. Holmium laser enucleation for prostate adenoma greater than 100 gm.: comparison to open prostatectomy. The Journal of urology. 2001;165(2):459-62.
15.
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. The Journal of urology. 2003;170(5):1847-50.
Table 1: Patients’ characteristics n
mean +/- SD
median
min - max
Age
100
70.9 +/- 9.0
70.4
46 - 100
Qmax (ml/s)
59
8.0 +/- 3.6
7.2
2 - 18
Prostate volume (cc)
97
60.0 +/- 17.2
60.0
27 - 122
Post-void residual (cc)
68
158.6 +/- 191.9
80.0
0 - 950
PSA (ng/ml)
85
4.02 +/- 4.77
3.0
0.06 – 39.1
I-PSS
79
19.9 +/- 7.1
21.0
5 - 34
DANSEX
59
13.3 +/- 18.6
8.0
0 - 81
Qmax: maximum uroflowmetry; SD: standard deviation; IPSS: international prostatic symptom score; DANSEX: Danish sex questionnaire PSA: prostate specific antigen
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Table 2. Primary outcome criteria Complete intervention with successful morcellation
N(%)
No
8 (8.4%)
Yes
87 (91.6%)
Complications during the procedure Yes
15 (15.5%)
None
82 (84.5%)
Operating time ≤ 90 minutes No
51 (52.6%)
Yes
46 (47.4%)
Stress ≤ 5/10 No
9 (9.6%)
Yes
85 (90.4%)
Difficulty ≤ 5/10 No
14 (15%)
Yes
80 (85%)
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Table 3. Operative characteristics Capsule localization
Enucleation
Hemostasis
Complete morcellation
Yes
93
77
86*
87
No
1
16
9
8
2.8 ± 1.8 [0-10]
4.8 ± 2.7 [1-10]
2.5 ± 2.0 [0-9]
3.1 ± 2.3 [0-10]
2.2 ± 1.8 [0-10]
3.3 ± 2.4 [0-10]
2.0 ± 1.8 [0-8]
2.6 ± 2.2 [0-10]
5.8 ± 4.3 [0-26]
Right lobe (88%)
9.6 ± 7.9 [2-45]
13.5 ± 12.7 [1-70]
29.2 ± 16.4 [7-90]
Resection loop used in 14% of cases
Difficulty (0-10) Stress (0-10) Time (minutes)
Left lobe (96%) 32.9 ± 20.1 [5-105] Median lobe (12%) 20.7 ± 12.0 [5-71]
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Table 4: peri-operative data n
mean +/- SD
median
min - max
Duration of the complete procedure (min)
97
106.5 +/- 46.8
95.0
20 - 240
Energy delivered to the prostate (kJ)
93
148.05 +/- 100.2
145.0
2.0 – 474.0
Length of laser use (min)
62
82.5 +/- 33.4
75.0
20 - 160
Resected tissue weight (g)
96
30.5 +/- 19.3
26.5
4 - 90
Duration of post-operative bladder irrigation (h)
81
22.1 +/- 22.1
17.5
2 - 148
Volume of post-operative bladder irrigation
76
39.4 +/- 205.5
12.0
1 - 1800
Duration of bladder catheterization (h)
89
47.4 +/- 29.1
43.0
15 - 159
Duration of hospital stay (d)
98
4.1 +/- 1.8
4.0
2-9
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Received Date : 11-Dec-2014 Revised Date : 05-Mar-2015 Accepted Date : 11-Mar-2015 Article type
: Original Article
Multicenter prospective evaluation of the learning curve of the holmium laser enucleation of the prostate (HoLEP)
Grégoire Roberta, Jean-Nicolas Cornub, Marc Fourmarierc, Christian Saussined, Aurélien Descazeaude, Abdel Rahmène Azzouzif, Eric Vicautg, Bertrand Lukacsb.
Affiliations a
Service d’urologie, université Bordeaux Segalen, CHU de Bordeaux, 2, Victor-Segalen, 33076, Bordeaux cedex, France b
Service d’urologie, Hôpital Tenon, Université Paris-6, Assistance publique—Hôpitaux de Paris, 75020 Paris, France c
Service d’urologie, centre hospitalier Aix-en-Provence, 13616 Aix-en-Provence, France
d
Service d’urologie, NHC, 1 place de l’hôpital, 67091 Strasbourg, France
e
Service de chirurgie urologique, hôpital Dupuytren, CHU de Limoges, 2, avenue
Martin-Luther-King, 87042 Limoges, France f
Service d’urologie, CHU d’Angers, 49933 Angers, France
g
Clinical Research Unit, Lariboisière-Fernand Widal Hospital, Assistance publique Hopitaux de Paris; University Paris Diderot, Paris, France
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bju.13124 This article is protected by copyright. All rights reserved.
Accepted Article
Corresponding Author: Bertrand Lukacs Department of Urology Tenon Hospital 4 rue de la Chine 75020 Paris, France Tel: +33156016495 Fax : +33156017306 Email: [email protected]
Keywords : prostate, enucleation, HoLEP, holmium, learning curve, prospective study.
Abstract Objectives: • To describe the step-by-step learning curve of Holmium Laser Enucleation (HoLEP) surgical technique. Patients and methods: • A prospective, multicentrer observational study was conducted, involving surgeons experienced in transurethral resection of the prostate and open prostatectomy, never having performed HoLEP were included. • The main judgment criterion was the ability of the surgeon to perform four consecutive successful procedures, defined by the following: complete enucleation and morcellation, within less than 90 minutes, without any conversion to standard
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TURP, with acceptable stress, and with acceptable difficulty (evaluated by Likert scales). Each surgeon included 20 consecutive cases. Results: • Of nine centers, three abandoned the procedure before the end of the study due to complications, and one was excluded for treating patients off protocol. • Only one centre achieved the main judgment criterion of four consecutive successful procedures. Overall, the procedures were successfully performed in 43.6% of cases. • Reasons for unsuccessful procedures were mainly operative time longer than 90 minutes (n=51), followed by conversion to TURP (n=14), incomplete morcellation (n=8), significant stress (n=9), or difficulty (n=14) during procedure. • Ignoring operating time , 64% of procedures were successful and four out of five centers did 4 consecutive successful cases. • Of the five centers who completed the study, four chose to continue HoLEP. Conclusion: • Even in a prospective training structure, HoLEP has a steep learning curve exceeding 20 cases, with almost half of our centres choosing to abandon or not to continue with the technique. Operating time and difficulty of the enucleation seem the most important problems for a beginner. A more intensely mentored and structured mentorship programme might allow safer adoption of the operation.
This article is protected by copyright. All rights reserved.
Accepted Article
Introduction Holmium laser enucleation of the prostate (HoLEP) was first described in 1995 (1), and is considered as a first line surgical option for transurethral relief of benign prostatic obstruction (BPO) (2). HoLEP has been shown in level 1 studies to have several advantages compared to transurethral resection of the prostate (TURP), including shorter hospital stay, reduced bleeding complications, absence of TURP-syndrome (3). Furthermore, functional outcomes of HoLEP have been stated to at least as good as after TURP, and comparable to those obtained with open prostatectomy (OP) for larger prostates (3, 4). HoLEP is thus often considered as a “new gold standard” by several authors (5, 6). However, in many centers, HoLEP has not yet replaced TURP and OP (7). HoLEP being seen as a more difficult and lengthy procedure, learning curve has been pointed out as a limitation for a high diffusion of this surgical technique now described 15 years ago (8-10). But to date, no study has been really focused on a detailed evaluation of the learning curve. Our goal was to describe the step-by-step learning curve of HoLEP surgical technique through a prospective, multicentrer observational study, based on pre-specified operative parameters.
Material and methods Study design. A prospective, multicentre clinical study was conducted in nine reference centres for LUTS/BPO management between March 2012 and July 2013. In each participating center, one surgeon was identified as being the local investigator. Participating
This article is protected by copyright. All rights reserved.
Accepted Article
surgeons had to fulfill the following criteria: willing to learn HoLEP technique, having no experience with HoLEP, having previous experience in TURP and OP. All surgeons had to complete an initiation training phase before beginning the trial. During this phase, all surgeons received a detailed course explaining the technique and a booklet describing the technical steps of the procedure. All centres were equipped with the Lumenis™ 100W laser generator and with a complete set of endoscopic instrumentation including the Piranha™ morcellator manufactured by Richard Wolf™. The surgeons received technical instructions from an expert and were mentored for the first 2 cases. No additional technical support was provided after the first two cases. The procedures were conducted as previously described (11, 12). Patients inclusion criteria. Patients were eligible to enter the study if aged of more than 50, showing an International Prostate Symptom Score (I-PSS) > 12, IPSS question 8> 3, maximum urinary flow rate (Qmax) under 12 ml/s, estimated prostate weight between 40 and 80 g and post-void residual volume of less than 300cc. Patients with any history of prostatic surgery, proven prostate cancer or ongoing anticoagulant therapy were excluded form the study. Pre-operative work-up included assessment of the following parameters: I-PSS symptom score, I-PSS bother score, DAN-PSSsex score, Global sexual satisfaction, quality of life score, urinary flow rate, postvoid residual volume, ultrasound examination of the prostate and PSA blood testing. All patients gave written informed consent to participate. Evaluation criteria. Main outcomes were based on operative parameters. The main judgment criterion was the ability of the surgeon to perform four consecutive successful procedures.
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Accepted Article
The definition of a successful procedure (composite criterion) was a combination of complete enucleation and morcellation, within less than 90 minutes, without any conversion to standard TURP, with acceptable stress, and with acceptable difficulty. Stress and difficulty of the procedure were assessed by the surgeon himself, using a visual analogic scale and were considered acceptable if under 5/10.Time, stress and difficulty had to be evaluated for the five separated steps of the procedure: contact with the prostatic capsule, enucleation of the median lobe, enucleation of the lateral lobes, haemostasis, and morcellation. Secondary judgment criteria included operative parameters (laser data (duration, Joules number of fibers used, fibre type, morcellator and nephroscope type), tissue weight, irrigation volume, need for coagulation with another device, adverse events during the procedure, duration of the catheterization, post-operative irrigation (duration, volume, type), and hospital stay. A post-operative visit was scheduled at one, six and twelve month for evaluation of efficacy and delayed complications, but was not part of the current evaluation.
Statistical analyses Based on previously published studies evaluating the learning curve of the HoLEP procedure (8, 11, 13, 14), we decided to include 20 consecutive patients for each participating surgeon after the first two mentored cases. Descriptive analyses were conducted for all parameters. Results Nine surgeons from nine centers participated in this study. None of them had any previous experience with the HoLEP procedure. Four centers were excluded for the following reasons:
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one stopped after two patients without further explanation, one decided to give up after the first patient experienced severe stress urinary incontinence, one stopped the study because was not confident with the surgical technique, and another one treated patients by HoLEP outside the protocol during the study period, which was judged as a major protocol violation. Hence, five surgeons who treated 20 patients each were considered for the final analysis. The surgeons were aged 33 to 53 and had various experience with BPH surgery (2 of them had performed less than 50 TURP and less than 50 simple prostatectomies). Depending on the surgeon the inclusions lasted from 3 to 10 months from the first to the last patient. Two patients withdrew their consent before being operated. Patient characteristics are shown in table 1. Thirty-two patients had a urinary catheter before surgery due to urinary retention. Sixty-five patients had history of any cardiovascular disease, but no patient was receiving anti-coagulant or platelet aggregation inhibitors before surgery. A single surgeon achieved the main judgement criterion of four consecutive successful procedures. The total number of consecutive successful procedures was 6 for one surgeon, 3 for 3 surgeons and 1 for 1 surgeon. The total number of successful procedures ranged from 3 to 12 depending on the surgeon. Overall, the procedures were successfully performed in 43.6% of cases. Reasons for unsuccessful procedures were: operative time longer than 90 minutes (n=51), conversion to TURP (n=14), incomplete morcellation (n=8), significant stress (n=9), or difficulty (n=14) during procedure. In 21 cases, there were two reasons or more for failure. Operative parameters (main outcomes) are detailed in table 2 and 3. The mean duration of the This article is protected by copyright. All rights reserved.
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complete procedure was 106.5 minutes. Conversion to TURP was necessary in 14 cases either for coagulation (2 cases), resection of remaining tissue (10 cases) or for both reasons (1 case). In one additional case the laser device failed during the procedure, needing interruption of the laser enucleation and conversion to TURP (this case was included as a failure, possibly impacting the results of the consecutive cases in this specific center). Conversion to TURP occurred in four different centres.
Peri-operative data are displayed in table 4. The mean post-operative duration of haematuria was 67.4±111.2 hours. Twenty-three patients encountered prolonged postoperative bleeding requiring maintenance of bladder irrigation and/or bladder clots removal during post-operative period. None of them had to be re-operated. Transfusion was necessary in one patient. Urinary tract infection was reported in 5 patients. All patients were discharged without urinary catheter.
Discussion With only one surgeon achieving to complete four consecutive successful procedures, our results confirmed that the HoLEP learning curve is at least of 20 procedures, underlying the difficulty for the surgeon to get confidence, and speed at the beginning of surgical experience. Such global results have already been stated by others in other studies. Shah et al evaluated the learning curve of an experienced endourologist (10). They prospectively collected data from the first 160 cases and concluded the enucleation and morcellation efficiency reached
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a plateau after 50 cases. Placer et al retrospectively analysed their results with 125 consecutive patients operated by a single surgeon (9). Once again, they found enucleation and morcellation efficiency rates improved significantly after the first 50 cases. Seki et al, in a retrospective evaluation, have shown that enucleation efficacy increased during the first 70 cases (15). However, none of these studies were designed to detail the learning curve and the steps limiting the ability of the surgeon to conduct successful procedures. In the present study, we focused the primary outcome of our prospective evaluation on the learning curve itself and were able to identify the parameters influencing successful outcomes. The main parameter that led to unsuccessful procedure as defined by the protocol was the operating time. Indeed, considering that an acceptable time to complete the whole procedure would be 120 minutes rather than 90 minutes, would lead to 61.7% success rate and to 4 different surgeons achieving to complete 4 consecutive successful procedures instead of one. The rather stringent criterion of 90 minutes was based on the experience gained with practice of TURP and upon advice of experts of HoLEP, but this cut-off might be not the best one at the beginning of surgical experience, when the surgeons are even not really familiar with the device. However, difficulty of the procedure was also perceived as a limitation, more than stress of the surgeon. According to the detailed, step by step evaluation, enucleation itself was seen as the most difficult part (table 3). According to the investigators’ experience, enucleation of the median lobe was always easier than lateral lobes, and as such, enucleation of solely the median lobe might be a useful option at the beginning of the learning curve.
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Laser failure occurred in one patient and might have impact the curve for one center, as this case was considered as a failure because converted to TURP). Once again, the stringent criteria of the study have to be considered when analysing the data. Despite these initial results, four of the five centers decided to continue to use HoLEP and increased their experience. The one who stopped did not continue to use the technique because the healthcare center was not able to get the laser equipment, but was keen to continue the technique. Hence, if 20 cases are probably not enough to overcome the learning curve (despite this cut-off has been proposed by some HoLEP users) 20 cases are probably sufficient to give the surgeon the willingness to continue with the technique. Furthermore, it does suggest that more closely supervised training programmes may help new users deliver efficiency and patient safety than more “traditional” approaches.
Our results emphasize the fact that HoLEP is quite difficult for beginners and has a steep learning curve. The participating surgeons did not receive any technical assistance after the first two cases did, and the present data indirectly confirm, although without a comparison group, that mentorship should be useful for optimization of the learning curve and prevent some drop outs, as already suggested by others (11, 12). Our detailed evaluation may be a useful tool to monitor the evolution of the surgeon’s performance during the learning period, as detailed technical steps have been recently reviewed but not subjected to separate, individualized evaluation. Our study has several limitations. First, not all the centres completed the study, but the exclusion of some centres gives in itself important information. For various reasons, 3 out of 10 surgeons, initially motivated to develop the technique have stopped the trial, that This article is protected by copyright. All rights reserved.
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highlight the fact that alone, without mentorship or motivated co-workers, a surgeon is at risk to abandon the technique and get back to previous gold standard. Then, our study was focused on operative parameters and it should be useful to assess the efficacy outcomes and complications, to see if they are impacted by the learning curve, as postulated by previous studies (15). Notably, detailed clinical data about cases treated by HoLEP in the four centers excluded were nt included in the present analysis, which should be seen as a drawback as the study is to be analysed in intent to treat. However, complications in these patients were limited to one severe case of urinary incontinence, as previously mentioned. Furthermore, the inclusion of patients with catheter in place pre-operatively may have influenced the results as these patients have usually more vascular glands. Another potential limitation is that 20 cases appears not enough to get out of the learning curve, and the inclusion of more patients in each centre may have been even more demonstrative.
Conclusion HoLEP learning curve is known to be steep; in our experience it exceeds 20 procedures for most of surgeons. Through a detailed, prospective evaluation of the different technical steps of the procedure, we were able to show that excessive operating time and difficulty of the enucleation itself are the most important limitation to overcome for a beginner. Such detailed evaluation could be useful in a structured mentorship programme.
Acknowledgements: This study was conducted based on a grant from the French Ministry of Health (STIC).
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The authors would like to thank Lumenis and EDAP-TMS for their technical assistance.
Links of interest: Christian Saussine receives consultancies from GSK and Lilly, and is investigator for AMS and EDAP-TMS. Marc Fourmarier is proctor for EDAP-TMS and speaker fro Lumenis. Jean-Nicolas Cornu has received research funding from Assistance Publique Hôpitaux de Paris, French Ministry of Health, Oak Ridge Associated Universities, the Association Française d'Urologie and GSK, and has received consultancies and travel grants from Bard, AMS, EDAPTMS, Coloplast, Pfizer, MundiPharma, Astellas, Bouchara-Recordati, Biocompatibples UK and Takeda, and is proctor for AMS.
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Table 1: Patients’ characteristics n
mean +/- SD
median
min - max
Age
100
70.9 +/- 9.0
70.4
46 - 100
Qmax (ml/s)
59
8.0 +/- 3.6
7.2
2 - 18
Prostate volume (cc)
97
60.0 +/- 17.2
60.0
27 - 122
Post-void residual (cc)
68
158.6 +/- 191.9
80.0
0 - 950
PSA (ng/ml)
85
4.02 +/- 4.77
3.0
0.06 – 39.1
I-PSS
79
19.9 +/- 7.1
21.0
5 - 34
DANSEX
59
13.3 +/- 18.6
8.0
0 - 81
Qmax: maximum uroflowmetry; SD: standard deviation; IPSS: international prostatic symptom score; DANSEX: Danish sex questionnaire PSA: prostate specific antigen
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Table 2. Primary outcome criteria Complete intervention with successful morcellation
N(%)
No
8 (8.4%)
Yes
87 (91.6%)
Complications during the procedure Yes
15 (15.5%)
None
82 (84.5%)
Operating time ≤ 90 minutes No
51 (52.6%)
Yes
46 (47.4%)
Stress ≤ 5/10 No
9 (9.6%)
Yes
85 (90.4%)
Difficulty ≤ 5/10 No
14 (15%)
Yes
80 (85%)
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Table 3. Operative characteristics Capsule localization
Enucleation
Hemostasis
Complete morcellation
Yes
93
77
86*
87
No
1
16
9
8
2.8 ± 1.8 [0-10]
4.8 ± 2.7 [1-10]
2.5 ± 2.0 [0-9]
3.1 ± 2.3 [0-10]
2.2 ± 1.8 [0-10]
3.3 ± 2.4 [0-10]
2.0 ± 1.8 [0-8]
2.6 ± 2.2 [0-10]
5.8 ± 4.3 [0-26]
Right lobe (88%)
9.6 ± 7.9 [2-45]
13.5 ± 12.7 [1-70]
29.2 ± 16.4 [7-90]
Resection loop used in 14% of cases
Difficulty (0-10) Stress (0-10) Time (minutes)
Left lobe (96%) 32.9 ± 20.1 [5-105] Median lobe (12%) 20.7 ± 12.0 [5-71]
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Table 4: peri-operative data n
mean +/- SD
median
min - max
Duration of the complete procedure (min)
97
106.5 +/- 46.8
95.0
20 - 240
Energy delivered to the prostate (kJ)
93
148.05 +/- 100.2
145.0
2.0 – 474.0
Length of laser use (min)
62
82.5 +/- 33.4
75.0
20 - 160
Resected tissue weight (g)
96
30.5 +/- 19.3
26.5
4 - 90
Duration of post-operative bladder irrigation (h)
81
22.1 +/- 22.1
17.5
2 - 148
Volume of post-operative bladder irrigation
76
39.4 +/- 205.5
12.0
1 - 1800
Duration of bladder catheterization (h)
89
47.4 +/- 29.1
43.0
15 - 159
Duration of hospital stay (d)
98
4.1 +/- 1.8
4.0
2-9
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