Holmium Laser Enucleation of the Prostate (HoLEP): The Endourologic Alternative to Open Prostatectomy

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1 european urology xxx (2005) xxx xxx available at journal homepage: BPH Holmium Laser Enucleation of the Prostate (HoLEP): The Endourologic Alternative to Open Prostatectomy Ehab A. Elzayat, Mostafa M. Elhilali * Division of Urology, McGill University School of Medicine, Montreal, QC, Canada Article info Article history: Accepted August 17, 2005 Published online ahead of print on November 2, 2005 Keywords: HoLEP Large prostate Open prostatectomy Abstract Objective: To evaluate HoLEP for patients with enlarged prostate (traditionally treated by open prostatectomy) with long-term follow-up. Methods: A retrospective analysis of 225 consecutive patients presenting with lower urinary symptoms secondary to benign prostatic hyperplasia with large prostate (>80 cc) who underwent HoLEP. Enucleation time, morcellation time, enucleated tissue weight, catheterization time, hospital stay, voiding outcome parameters, and complications were recorded. Results: Mean preoperative prostate volume was cc (range , median cc), and resected tissue weight was 86.5 g. Mean follow-up was months (median 24 months). Mean catheter time and hospital stay were 1.3 and 1.2 days, respectively. Patient symptom scores and peak flow rates were significantly improved immediately after surgery and continued to improve during subsequent follow up. Two patients required intraoperative blood transfusion, and a third patient needed blood transfusion in the early postoperative period for persistent hematuria. Bladder neck contracture and urethral stricture developed in 0.4% and 1.3%, respectively. Conclusions: HoLEP represents a safe and effective treatment for patients with symptomatic large prostates. It offers patients who traditionally required open prostatectomy the alternative of being treated endoscopically with minimal blood loss, short catheterization time and hospital stay. # 2005 Elsevier B.V. All rights reserved. Please visit to read and answer the EU*ACME questions on-line. The EU*ACME credits will then be attributed automatically. * Corresponding author. Present address: Urology Division, Department of Surgery, MUHC- Royal Victoria Hospital, Room S6.95, 687 Pine Avenue West, Montreal, Quebec, Canada, H3A 1A1. Tel ; Fax: address: mostafa.elhilali@muhc.mcgill.ca (M.M. Elhilali). 1. Introduction Most minimally invasive techniques represent an alternative to transurethral resection of the prostate (TURP) for small size prostates; however, the classical treatment of large prostates is limited to either staged TURP or open prostatectomy. Large prostates require longer resection time and are /$ see front matter# 2005 Elsevier B.V. All rights reserved. doi: /j.eururo EURURO-998; No of Pages 5

2 2 european urology xxx (2005) xxx xxx associated with increased blood loss as well as higher risk of transurethral resection (TUR) syndrome, and thus open surgery is considered a better option [1]. Open prostatectomy is performed less frequently in the U.S. (fewer than 3% of prostatectomies) because of the relatively low incidence of large size prostates [2]. This is, however, changing as more patients are being kept on alpha-blockers before being considered for surgery with resultant larger size glands. Still, open prostatectomy is used more often than many might believe in some developed countries with an incidence rate ranging between 12% to 32% of prostatectomies performed for benign prostatic hyperplasia (BPH) [3 5]. However, open prostatectomy is an invasive procedure, associated with significant morbidity, and requires a lower abdominal incision, with consequently longer hospitalization and convalescence periods. HoLEP is the most recent step in the evolution of holmium laser prostatectomy. Refinement of the holmium laser technique and development of an efficient tissue morcellator have led to the true anatomic enucleation of prostatic adenomas of any size [6]. Gilling et al. [7] reported on 43 patients with preoperative prostate volume >100 g, and concluded that the holmium:yag laser can be used to enucleate the adenomas of a large prostate in much the same way as the surgeon s finger does during open prostatectomy. The technique allows peeling the median and lateral lobes off the surgical capsule [7]. Kuntz and Lehrich undertook a randomized study comparing HoLEP and transvesical prostatectomy, finding that both procedures are equally effective with less perioperative morbidity in the HoLEP group [8]. The reports that evaluated HoLEP in patients with large prostates included a small number of patients with short-term follow-up. The aim of the present study is to evaluate HoLEP in patients with large prostates in a large series and to provide long-term follow-up. 2. Materials and methods This is a retrospective analysis of 225 consecutive patients presenting with symptomatic large prostate (>80 cc) and undergoing HoLEP between March 1998 and April 2005 at our institution. Patients were excluded from the study if they had been previously diagnosed with prostate cancer or neurogenic bladder. All laser surgeries were performed or supervised by a single surgeon (MME). The equipment used was: an watt holmium:yag laser (Versapulse, Lumenis Inc., Santa Clara, CA, USA); a 550-mm end-firing fibre (SlimLine TM 550, Lumenis Inc.); a modified continuous-flow 26 F resectoscope with a distal bridge; a 7 F catheter through the proximal bridge to stabilize the laser fibre; continuous saline irrigation; a rigid indirect nephroscope with a 5-mm working channel; a tissue morcellator (Lumenis Inc.); and a video system. HoLEP was undertaken as described previously [9 11]. Briefly, the 2-lobe technique starts with a 5- or 7-O clock incision with enucleation of 1 lateral lobe, followed by the median and remaining lateral lobes as a single unit into the bladder. The 3-lobe technique is suited for a large gland with a large median lobe. This involves 5- and 7- O clock incisions with enucleation of the middle lobe and subsequent enucleation of 1 lateral lobe followed by the other lateral lobe. The procedure is performed at a laser setting of 2 Joules and 50 Hertz for enucleation, and 2 Joules and 40 Hertz for apical dissection and to release the lobes from the sphincter. If bleeding is encountered, the laser fibre can be defocused slightly from the bleeding point to achieve hemostasis. Coagulation can be optimized by reducing the laser setting to 1.5 Joules and 30 Hertz. Furosemide is administered (20 mg/ h of enucleation, intravenously), which, in most cases, coincides with the end of enucleation to counteract any fluid absorption and to enhance urine flow. After enucleation and morcellation of the prostate, a standard 22 F 2-way catheter is inserted and connected to straight drainage, unless the degree of hematuria requires bladder irrigation. Intermittent bladder irrigation is delivered through a Y-connector. On rare occasions, if the hematuria persists despite intermittent irrigation, continuous irrigation was instituted by a 3-way catheter. Routinely, the catheter is removed the next morning, and when the patient is able to void adequately, he is discharged from the hospital. Mean peak flow rate (Qmax) values and postvoid residual urine (PVR), international prostate symptom score (IPSS), and quality of life score (QoL) were compared before surgery and postoperatively by paired Student s t-test. p < 0.05 was considered significant. 3. Results Mean age of the 225 patients was 73.7 years (range, 52 94). Mean preoperative transrectal ultrasound (TRUS) sizing of prostate volume was cc (range ). Patient baseline characteristics and indications for surgery are enumerated in Table 1. Fiftyfour percent of patients presented with symptomatic BPH refractory to medical treatment, and 45% presented with urinary retention and failed repeated trials of voiding without a catheter on alpha-blocker therapy. The procedure was preceded by laser lithotripsy of bladder calculi in 19 patients, followed by diverticulectomy in 1 patient. Another patient required perineal urethrotomy at the time of surgery, as the length of the resectoscope was not sufficient to perform the enucleation. The resected tissue weight was 86.5 gm (range from )(Table 2). The weight of the enucleated tissues

3 european urology xxx (2005) xxx xxx 3 Table 1 Baseline characteristics of patients who underwent HoLEP Characteristics Age 73.7 (52 94) Indications of surgery LUTS 121 (53.8%) Urinary retention 102 (45.3%) Hematuria 2 (0.9%) TRUS volume (cc) (80 351) Preoperative PSA (ng/ml) 9 ( ) Preoperative IPSS 18.7 (8 35) Preoperative QoL 3.7 (1 6) Preoperative Qmax (ml/sec) 8 (0 15) Preoperative PVR (ml) (14 2,000) was underestimated as a significant amount of tissue was vaporized in the process. Eight patients (3.5%) required a small cystostomy incision because of the presense of multiple bladder stones in 1 patient, inadequate morcellation progress in 3 patients, and the large size of the adenoma, ranging from 170 to 351 gm, in 4 patients. In these patients, a large prostate volume occupied most of the bladder volume, leaving inadequate space for safe morcellation. Mucosal bladder injuries were encountered in 2 patients during morcellation. Prolonged catheterization in these patients was required. Continuous bladder irrigation was necessary in 8 patients (3.5%) for transient postoperative hematuria. Only 2 patients required intraoperative blood transfusion. However, early postoperative blood transfusions were needed in 1 patient for persistent hematuria. Mean preoperative and postoperative hemoglobin values were and g/l, respectively. Mean preoperative and postoperative serum sodium values were and mmol/l, respectively ( p = 0.24). No patient experienced any symptoms of dilutional hyponatremia or TUR syndrome as saline was used as irrigant during HoLEP. One patient developed clot retention 1 week postoperatively and required readmission for cystoscopy and bladder irrigation. Mean catheterization time was 1.3 days (range 1 17), and mean hospital stay was 1.2 days (range 1 9). More than 86% of Table 2 Mean operative data Variable Mean (range) Enucleation time (min) (30 255) Morcellation time (min) (3 120) Enucleated tissue weight (gm) (25 340) Total energy used (kj) ( ) Catheterization time (day) 1.3 (1 17) Hospital stay (day) 1.2 (1 9) patients were discharged home within 24 h after surgery. Longer hospital stay was usually required if the patient had a postoperative complication or associated medical condition. Mean prostate-specific antigen (PSA) decreased from 9 ng/ml (range 0.41 to 55) to 0.91 ng/ml (range 0.07 to 9.5) at 6 months postoperatively ( p < ). Pathology examination of the enucleated tissue revealed BPH in 217 patients and prostatic adenocarcinoma in 5 patients (2.2%), high-grade prostatic intraepithelial neoplasia (PIN) in 1 patient and lowgrade PIN in 2 others. All patients were followed up with expectant management; the pathology in their prostates was focal and of low Gleason score. Qmax, PVR, IPSS, and QoL score were significantly improved immediately after surgery and continued to do so during subsequent follow-up (Table 3). At 3 years postoperatively, Qmax increased from 8.09 to 28.5 ml/sec ( p < ) and PVR decreased from 325 to 46.1 ml ( p < ). IPSS improved from 18.7 to 3.7 ( p < ), and QoL score, from 3.7 to 0.7 ( p < ). Twenty-one patients (9.3%) had postoperative irritative symptoms which required occasionally anticholinergic therapy. Sixteen patients (7.1%) had stress urinary incontinence (SUI), which resolved in 12 of them within 1 to 6 months. Four patients (1.8%) had mild SUI at the last follow-up; 2 of them are still within 6 months after surgery, and the remaining 2 patients still have SUI at 10 months postoperatively. Four patients had urge urinary incontinence; 2 of them still had urge incontinence at last follow-up. One of these 2 patients had persistent urge incontinence due to overactive bladder; the other patient is at 4 months postoperatively. Urinary tract infections (UTI) developed in 4 patients (1.7%) and were treated with proper antibiotics. Urethral strictures occurred in 3 patients (1.3%), and meatal stenosis in 1 patient. Bladder neck contracture was noted in 1 patient (0.4%) at 2 years after surgery and treated successfully by laser incision of the bladder neck. 4. Discussion Open prostatectomy is the oldest invasive treatment of symptomatic BPH. Despite the successful results and low reoperation rates of open prostatectomy, it is still associated with a high incidence of intraoperative bleeding, blood transfusions and some mortality. The mortality rate in the early years was about 10% and dropped to 2% by the early 1950s with the advent of better preoperative evaluation and anesthesia [12]. Complications for open pros-

4 4 declined by 86.7%, and the IPSS decreased by 80%. The dramatic reduction of PSA ( 90%) after HoLEP confirmed the near complete removal of prostatic adenoma. The results of our study are similar to previous reports on HoLEP for large prostates. Hettiarachchi et al. [16] investigated 18 patients with prostate volume greater than 100 cc who underwent HoLEP. Mean preoperative prostate volume was cc, and specimen weight was 82.7 gm. None of the patients required blood transfusions. Bladder neck contracture and urethral stricture developed in 1 patient each at 16 months after HoLEP. The low percentage of completed follow-ups in this study is mainly because a high percentage of our patients are referred to us from another cities or states, and they are subsequently followed up by their local urologist. In a randomized study comparing HoLEP (n = 60) and transvesical prostatectomy (n = 60) for prostates exceeding 100 cc, Kuntz and Lehrich [8] found that both procedures are equally effective with less perioperative morbidity in the HoLEP group. The blood transfusion rate was 13% in the open prostatectomy group and none in the HoLEP group. The amount of tissue retrieved was 83.9 gm, which is similar to our results and less than 96.4 gm retrieved after open prostatectomy. Operative time was longer than that in our report and open prostatectomy group (135.9 vs min). In a small series Moody and Lingeman [17] compared HoLEP (n = 10) and open prostatectomy (n = 10), finding no significant difference in operative time between the two procedures, but resected tissue weight was greater in the laser group (151 vs. 106 gm, p = 0.067). The length of hospital stay was shorter in the HoLEP group with no need for blood transfusion however; 3 out of 10 patients required blood transfusion after open prostatectomy. The initial cost of holmium laser equipment is significant, but nowadays it is available in most urology centers. The holmium laser has many other applications, such as the incision of urethral and ureteral strictures, lithotripsy of urinary calculi, and ablation of superficial urothelial tumors. The multifunctional nature of holmium laser makes it costeuropean urology xxx (2005) xxx xxx Table 3 Preoperative data and follow-up changes after HoLEP (No) Mean Qmax (ml/sec) Mean PVR (ml) Mean IPSS Mean QoL score Preoperative (155) 8.09 (0 15) 325 (14 2,000) 18.7 (8 35) 3.7 (1 6) 1 month (174) ( ) 46.8 (0 301) 6.2 (0 28) 1.3 (0 6) 3 months(135) 25.7 (8.5 67) 32.4 (0 209) 4.5 (0 17) 1.02 (0 5) 6 months (128) 26.4 (6.3 78) 28.8 (0 292) 3.6 (0 17) 0.82 (0 5) 1 year (105) (5.5 70) 29.7 (0 380) 3.9 (0 21) 0.8 (0 6) 2 years (62) (6.8 72) 37 (0 238) 3.5 (0 19) 0.7 (0 4) 3 years (31) 28.5 (5.1 71) 46.1 (0 183) 3.7 (0 26) 0.7 (0 4) tatectomy ranged from 10% to 40%, with recent series near 15%. Serretta et al. [5] reported on 1,804 patients who underwent open prostatectomy. The rates of severe bleeding, blood transfusion, and sepsis were 11.6%, 8.2%, and 8.6%, respectively. Others noted a blood transfusion rate of 26.5% after open prostatectomy [13]. The high incidence of postoperative bleeding leads to a high incidence of clot retention (6.7%) [14]. In our study, the rate of blood transfusion was 1.3%, which is lower than in the contemporary series of Serretta et al., even though mean prostate volume in our study was larger (126 vs. 70 cc). Catheterization time and hospital stay after open surgery are longer than with TURP and vary from 5 to 7 days and from 6 to 10 days respectively [5,14]. Longer catheterization and hospital stay may be attributed to a high incidence of infection after open surgery. The incidence of wound infection and leakage varied from 2% to 6.9% [12,15]. UTI rates of 2.6% to 8.6% were reported. The incidence of epididymo-orchitis was 1.3 to 4% [12 15]. HoLEP allows endoscopically anatomic enucleation of prostatic tissue of any size with excellent hemostatsis and a nearly bloodless field without need for open surgery and subsequently no wound complications. Catheterization time and hospital stay in our series were 1.3 and 1.2 days, respectively, with a very low incidence of UTI (1.7%). Varkarakis et al. [15] reported on 5-year follow-up of 232 patients who underwent open transvesical prostatectomy. The incidence of bladder neck contracture and urethral stricture was 3.3% and 1.9%, respectively. The reoperation rate was 3.9%, which is similar to that reported by Serretta et al. (3.6%) [5]. In the current study, the incidence of bladder neck contracture and urethral stricture was much lower than that reported after open surgery, and this could be attributed to the short catheterization time after HoLEP. One of the advantages of HoLEP is that it has no size limitation, with immediate and durable improvement of the symptoms and flow rate regardless of the size of the prostate. At 3 years postoperatively, Qmax increased by 255%, PVR

5 european urology xxx (2005) xxx xxx 5 effective. Fraundorfer et al. [18] compared HoLRP and TURP in terms of cost-effectiveness. They concluded that HoLRP offers 24.5% cost-saving over TURP, and when 93 procedures are performed annually, this would cover the initial and maintenance costs of the laser equipment. The longer operative time and prolonged learning curve are the main criticism of the HoLEP procedure. In our experience, HoLEP requires longer training than traditional surgery, and urologists become comfortable with the procedure after a mean of 20 to 30 cases with small- to moderate-sized prostates before attempting HoLEP of larger prostates. Some authors suggest that learning HoLEP is equivalent to learning TURP because it is a mostly bloodless procedure with clear visibility; however, close supervision of an experienced urologist is a prerequisite for success. 5. Conclusion HoLEP is a safe and effective treatment of symptomatic large prostate with no dilutional hyponatremia, minimal blood loss, short catheterization time, hospital stay and convalescence period. It allows patients with large prostates who traditionally require open prostatectomy to be treated endoscopically. It is reasonable to consider HoLEP to be the modern endourologic alternative to open prostatectomy. References [1] Mebust WK, Holtgrewe HL, Cockett AT, Peters PC, The Writing Committee. Transurethral prostatectomy: immediate and postoperative complications. A cooperative study of 13 participating institutions evaluating 3,885 patients. J Urol 1989;141: [2] Bruskewitz R. Management of symptomatic BPH in the US: who is treated and how? Eur Urol 1999;36(Suppl 3): [3] Ahlstrand C, Carlsson P, Jonsson B. An estimate of the lifetime cost of surgical treatment of patients with benign prostatic hyperplasia in Sweden. Scand J Urol Nephrol 1996;30: [4] Lukacs B. Management of symptomatic BPH in France: who is treated and how? Eur Urol 1999;36(Suppl 3): [5] Serretta V, Morgia G, Fondacaro L, Curto G, Lo Bianco A, Pirritano D. 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: [6] 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: [7] Gilling PJ, Kennett KM, Fraundorfer MR. Holmium laser enucleation of the prostate for glands larger than 100 g: an endourologic alternative to open prostatectomy. J Endourol 2000;14: [8] 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. J Urol 2002;168: [9] Gilling PJ, Cass CB, Cresswell MD, Fraundorfer MR. Holmium laser resection of the prostate: preliminary results of a new method for the treatment of benign prostatic hyperplasia. Urology 1996;47: [10] Fong BC, Elhilali MM. Video article. Ho:YAG laser enucleation of the prostate: technical details. BJU Int 2002;90: [11] Kuo RL, Paterson RF, Kim SC, Siqueira Jr TM, Elhilali MM, Lingeman JE. Holmium laser enucleation of the prostate (HoLEP): a technical update. World J Surg Oncol 2003;1(6):1 9. [12] Condie Jr JD, Cutherell L, Mian A. Suprapubic prostatectomy for benign prostatic hyperplasia in rural Asia: 200 consecutive cases. Urology 1999;54: [13] Mearini E, Marzi M, Mearini L, Zucchi A, Porena M. Open prostatectomy in benign prostatic hyperplasia: 10-year experience in Italy. Eur Urol 1998;34: [14] Meier DE, Tarpley JL, Imediegwu OO, Olaolorun DA, Nkor SK, Amao EA, et al. The outcome of suprapubic prostatectomy: a contemporary series in the developing world. Urology 1995;46:40 4. [15] 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: [16] Hettiarachchi JA, Samadi AA, Konno S, Das AK. Holmium laser enucleation for large (greater than 100 ml) prostate glands. Int J Urol 2002;9: [17] Moody JA, Lingeman JE. Holmium laser enucleation for prostate adenoma greater than 100 gm.: comparison to open prostatectomy. J Urol 2001;165: [18] 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.