- Email: [email protected]
Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on Safety and Outcomes
Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on Safety and Outcomes Pierre-Alain Hueber, Marc Nicolas Bienz, Roger Valdivieso, Hugo Lavigueur-Blouin, Vincent Misrai,* Matthew Rutman,† Alexis E. Te, Bilal Chughtai, Neil J. Barber, Amr M. Emara, Ravi Munver, Quoc-Dien Trinh‡ and Kevin C. Zorn*,§ From the Section of Urology, Department of Surgery, University of Montreal Hospital Center, Universite´ de Montre´al (PAH, MNB, RV, HL-B, KCZ), Montreal, Quebec, Canada, Departments of Urology, Clinique Pasteur Toulouse (VM), Toulouse, France, Columbia University (MR) and Cornell University (AET, BC), New York, New York, Frimley Park Hospital (NJB, AME), Frimley, United Kingdom, and Hackensack University Medical Center (RM), New Jersey, and Center for Surgery and Public Health and Division of Urological Surgery, Brigham and Women’s Hospital, Harvard Medical School (QDT), Boston, Massachusetts
Abbreviations and Acronyms BPH ¼ benign prostatic hyperplasia HoLEP ¼ holmium laser enucleation of prostate I-PSS ¼ International Prostate Symptom Score PSA ¼ prostate specific antigen PV ¼ prostate volume PVP ¼ photoselective vaporization of prostate PVR ¼ post-void residual urine volume Qmax ¼ maximum urinary flow rate QOL ¼ quality of life TRUS ¼ transrectal ultrasound TURP ¼ transurethral prostate resection XPS-180W ¼ GreenLight XPS 180 W system
Purpose: We evaluated photoselective vaporization of the prostate using the GreenLightÔ XPSÔ 180 W system for benign prostatic hyperplasia treatment in a large multi-institutional cohort at 2 years. We particularly examined safety, outcomes and the re-treatment rate in larger prostates, defined as a prostate volume of 80 cc or greater, to assess the potential of photoselective vaporization of the prostate as a size independent procedure. Materials and Methods: A total of 1,196 patients were treated at 6 international centers in Canada, the United States, France and England. All parameters were collected retrospectively, including complications, I-PSS, maximum urinary flow rate, post-void residual urine, prostate volume, prostate specific antigen and the endoscopic re-intervention rate. Subgroup stratified comparative analysis was performed according to preoperative prostate volume less than 80 vs 80 cc or greater on transrectal ultrasound. Results: Median prostate size was 50 cc in 387 patients and 108 cc in 741 in the prostate volume groups less than 80 and 80 cc or greater, respectively. The rate of conversion to transurethral prostate resection was significantly higher in the 80 cc or greater group than in the less than 80 cc group (8.4% vs 0.6%, p <0.01). I-PSS, quality of life score, maximum urinary flow rate and post-void residual urine were significantly improved compared to baseline at 6, 12 and 24 months of followup without significant differences between the prostate size groups. The re-treatment rate at 2 years reported in 5 of 411 patients was associated with the delivery of decreased energy density (2.1 vs 4.4 kJ/cc) in the group without re-treatment. Accepted for publication March 13, 2015. Study received institutional review board approval. * Financial interest and/or other relationship with American Medical Systems. † Financial interest and/or other relationship with American Medical Systems and Endo. ‡ Financial interest and/or other relationship with Intuitive Surgical. § Correspondence: University of Montreal Hospital Center, University of Montreal, Montreal, Quebec, Canada (e-mail: zorn.chumurology@ gmail.com).
Editor’s Note: This article is the fourth of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 602 and 603.
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0022-5347/15/1942-0462/0 THE JOURNAL OF UROLOGY® Ó 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2015.03.113 Vol. 194, 462-469, August 2015 Printed in U.S.A.
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Conclusions: Photoselective vaporization of the prostate using the XPS 180 W system is safe and efficacious, providing durable improvement in functional outcomes at 2 years independent of prostate size when treated with sufficient energy. Key Words: prostate, prostatic hyperplasia, laser therapy, volatilization, organ size
GREENLIGHT laser PVP as BPH treatment has significantly evolved in the last decade. The third generation XPS laser system introduced in 2010 features an increased laser beam diameter and a maximum power output to 180 W. Investigators reported that XPS-180W shows significantly decreased operative time and fiber use with increased energy delivery efficiency compared to the previous generation HPSÔ 120 W system.1,2 For earlier generations of the GreenLight laser system such as the HPS 120 W the higher re-treatment rate in patients with a prostate greater than 80 cc was attributed to insufficient adenoma removal.3e5 To our knowledge whether this limitation can be palliated using the novel XPS-180W remains to be determined. We prospectively assessed XPS-180W clinical outcomes at 2 years of followup in a large, multicenter, prospectively collected cohort. In particular special attention was given to the safety and durability of outcomes in patients with a large prostate (greater than 80 cc) to assess the potential of GreenLight PVP as a size independent procedure.
PATIENTS AND METHODS Study Population Eligible for study were all men with BPH who underwent Greenlight PVP using XPS-180W from May 2011 to May 2012, as performed by 1 of 7 high volume, experienced surgeons at a total of 6 sites in Canada, the United States, France and the United Kingdom. Excluded from study were patients with known prostate cancer, previous pelvic radiation or known neurological disorders. After receiving institutional board review approval 1,196 patients were identified. Indications for surgery in each country were based on similar criteria established by CUA (Canadian Urological Association), AUA (American Urological Association) and EAU (European Association of Urology) guidelines on BPH management.2
Surgical Procedure All patients underwent PVP as previously described using XPS-180W.6e8 Procedures were done according to published IGLU (International GreenLight User) guidelines and incorporated the technique and experience of the operating surgeon.9 Procedures were performed with the patient under general or spinal anesthesia and preoperative antibiotic prophylaxis was administered according to local guidelines. All surgeons were well beyond the learning curve for surgical technique and for several years
had used various previous generations of GreenLight systems (greater than 200 PVP procedures). In all cases a 23Fr continuous flow cystoscope with a 30-degree lens was used while being irrigated with room temperature saline. A working space was typically created initially at a power of 80 W. For the remainder of the procedure power was increased to 180 W adjusted in steps of 10 to 20 W. For coagulation the TruCoagÔ feature pulse was used, modulated at 12 Hz and 5 to 40 W. The MoXyÔ fibers were manufactured with a maximum energy delivery capacity of 650 kJ per unit. These fibers also featured a cooling system and a protective cap at the tip to minimize fiber devitrification. According to the manufacturer these features were designed to improve fiber durability and preserve optimal energy delivery on prostate tissue during the procedure.10 The intended surgical end point was tissue ablation down to the surgical capsule from bladder neck to verumontanum circumferentially to create the same defect as complete TURP.
Primary Outcomes Safety was evaluated by measuring the adverse events related to primary treatment. Efficacy was assessed by quantitative uroflowmetry parameter improvements as well as the subjective I-PSS score, including the QOL score, 6, 12 and 24 months after XPS-180W treatment. In addition, PSA reduction served as a surrogate marker of tissue removal.9 In 322 patients prostate size reduction was also determined by subtracting postoperative TRUS size at 3 months (6 to 12 weeks) from preoperative TRUS size. The endoscopic re-treatment rate was assessed 1 and 2 years after treatment. Subgroup comparative analysis was performed in patients with a prostate less than 80 vs 80 cc or greater as determined by preoperative TRUS PV. The effect of prostate size on safety efficacy and the re-treatment rate was examined.
Assessment We retrospectively collected preoperative data, including patient age and PV on TRUS, along with operative parameters, including total operative time, laser time, total energy use and number of fibers. Energy density was defined as the ratio of the amount of energy applied during treatment divided by prostate size defined according to preoperative TRUS measurements.
Statistical Analysis Parameters such as prostate size, energy and PSA were not normally distributed. Accordingly data are shown as the median and IQR. Because variables such as I-PSS or age were continuous data, they are shown as the mean and 95% CI. To compare the 2 groups of patients with a
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prostate less than 80 vs 80 cc or greater at baseline and at each followup end point the Mann-Whiney U test was used for median comparisons while the Student t-test was used for mean comparisons. To compare postoperative outcomes to baseline data the paired t-test or Wilcoxon test was done correspondingly. For categorical data the chi-square or Fisher test was used. Two-sided p <0.05 was considered statistically significant.
RESULTS A total of 1,196 patients underwent transurethral PVP. Table 1 lists institutions, locations and surgeons. Table 2 lists patient baseline characteristics. As defined by TRUS overall preoperative PV (median 61.4 cc) was only available in 1,128 patients with a median age of 70 years at surgery. Patient demographics were further stratified by PV less than 80 vs 80 cc or greater (table 2). Patients with a larger prostate were older with more severe lower urinary tract symptoms. They were more likely to be treated with BPH medication, including a-blockers and 5a-reductase inhibitors. Table 3 lists operative parameters. Overall procedure duration and energy use increased according to prostate size (less than 80 vs 80 cc or greater), corresponding to an energy density of 3.8 vs 3.25 kJ per prostate gm, respectively (p <0.01). The median number of fibers was generally 1 per case but this was slightly higher in the large prostate group (p <0.01). Hospital stay was 24 hours regardless of prostate size but mean catheterization duration was slightly longer, including 34 and 26 hours in the larger and smaller prostate groups, respectively (p <0.01). Table 4 lists the number of patients with at least 1 complication by Clavien-Dindo grade. Most complications were equivalent in the 2 groups (p >0.05). However, the incidence of conversion to TURP was significantly greater in the 80 cc or greater group compared to the less than 80 cc group (8.4% vs 0.6%, p <0.01). Multivariable regression analysis revealed that prostate size greater than 80 cc and lasing time were significant independent predictors of capsular perforation (table 5). I-PSS and QOL scores were significantly improved compared to baseline at 6, 12 and 24 Table 1. Distribution of 1,196 patients among institutions, surgeons and locations Institution University of Montreal, Montreal, Canada Columbia University, New York, New York Cornell University, New York, New York Frimley Park National Health Service, Frimley, United Kingdom Clinique Pasteur, Toulouse, France Hackensack University, Hackensack, New Jersey
No. Pts (%) 320 108 320 130
(27) (9) (27) (11)
231 (19) 85 (7)
Surgeons KCZ MR AET, BC NJB VM RM
months of followup without a significant difference between the prostate size groups in the change in I-PSS or QOL (paired test p <0.01, table 6). At 24 months for PV less than 80 vs 80 cc or greater the median I-PSS change was 17 vs 19 (p ¼ 0.14) and the median QOL score change was 3 vs 4 (p ¼ 0.8). Similarly median Qmax was increased at all endpoints compared to baseline (paired test p <0.01). At 24 months median Qmax was 19 ml per second for PV less than 80 and 80 cc or greater (p ¼ 0.9). PVR was improved in all patients regardless of prostate size at all endpoints compared to baseline (paired test p <0.01). The improvements were maintained up to 24 months (p ¼ 0.03, table 6). At 24 months the PVR change was 93.8% for PV less than 80 and 80 cc or greater (p ¼ 0.2). Median PSA was significantly higher in the larger prostate group at baseline and at all end points. The median PSA reduction expressed as a percent of the decrease was less in the 80 cc or greater prostate group at 6, 12 and 24 months (p <0.01). In a subset of 322 patients the PV change measured by the size difference between preoperative TRUS at baseline and TRUS measured 6 to 12 weeks postoperatively was also decreased more than 50% (part A of figure). However, this reduction was equivalent regardless of preoperative prostate size (53.8% vs 52.5% p ¼ 0.21). Similarly the PSA reduction at 3 months was equivalent between prostate size groups in this patient subset (52.4% vs 54.3%, p ¼ 0.8, part B of figure). The re-treatment rate at 12 and 24 months was less than 1% (4 of 462 patients) and 1.2% (5 of 411), respectively. Interestingly mean PV in the re-treated group was almost 120 cc, which was significantly larger than in the group without re-treatment. However, the energy delivered per prostate was lower in the re-treated group than in the group without re-treatment (2.1 vs 4.4 kJ/cc, p <0.01).
DISCUSSION In patients with a prostate greater than 80 to 100 cc who need BPH surgical treatment HoLEP is considered the laser therapy of choice as the only size independent procedure with demonstrated long-term functional outcomes and a true alternative to open prostatectomy. Growing evidence may also support the role of GreenLight PVP in the treatment of large prostates. Safety and short-term efficacy were observed in patients with a prostate up to 300 cc.11,12 However, in terms of prostatic tissue removal PVP is still considered less efficient than HoLEP or open prostatectomy.1,2,11,13 To date there are limited clinical data on PVP using the latest XPS system.2,14e17 The recent
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Table 2. Baseline characteristics overall and by PV subgroup PV (cc) Overall Median baseline (IQR)/No. pts:* Preop TRUS PV (cc) I-PSS QOL Qmax (ml/sec) PVR (ml) PSA (ng/ml) Age No. subgroup/total No. (%):† Acute urinary retention þ catheter Median lobe a-Blocker 5a-Reductase inhibitor ASAÒ physical status Clopidogrel Warfarin
Less Than 80
80 or Greater
p Value
61.4 (46)/1,128 22 (11)/996 5 (1)/1,021 6 (5)/970 151 (304)/945 3.0 (3.94)/791 70 (13)/1,190
50 (22)/741 21 (10)/645 5 (1)/651 6.8 (5)/625 150 (269)/613 2.4 (3.12)/537 69 (14)/740
108 (50)/387 24 (13)/308 5 (2)/328 5.0 (5)/309 211 (378)/290 4.6 (4.6)/253 71.6 (12)/383
<0.01 <0.01 0.01 <0.01 <0.01 <0.01 <0.01
222/1,196 220/508 853/1,195 589/1,189 326/1,196 53/1,196 76/1,196
136/739 126/739 557/739 318/739 202/739 33/739 47/739
86/387 93/387 265/387 228/387 103/387 16/387 25/387
0.08 <0.01 0.03 <0.01 0.7 0.8 0.9
(18.6) (43.3) (71.4) (49.5) (27.3) (4.4) (6.4)
(18.4) (17.1) (75.4) (43.0) (27.3) (4.5) (6.4)
(22.2) (24.0) (68.5) (58.9) (26.6) (4.1) (6.5)
* Mann-Whitney test p values. † Chi-square or Fisher test p values and total number of patients may not equal sum of subgroups due to loss at followup.
European randomized, controlled GOLIATH trial comparing XPS to TURP in men with BPH showed that XPS was not inferior to TURP based on I-PSS assessment at 6 and 12 months.18 However, this trial only included 136 patients treated with XPS and they had a relatively small prostate (mean PV 48.6 cc) while patients with a prostate greater than 100 cc were excluded.19,20 In the current study 387 patients with a prostate of 80 cc or greater were successfully treated with XPS-180W. As shown, energy use in kJ as a measured operative parameter was associated with preoperative PV in cc and the required delivered energy density ranged between 3 and 4 kJ/cc. In terms of efficacy, despite differences at baseline the improvements in I-PSS, QOL score, Qmax and PVR were equivalent between the groups at 24 months, confirming durable improvements in outcomes regardless of prostate size. In terms of safety, most complications were Clavien-Dindo grade I/II with no significant difference between the size groups. However, the incidence of conversion to TURP was significantly greater in the larger prostate group (8% for 80 cc
or greater vs 0.6% for less than 80 cc, p <0.01). Prostate size appeared to be an independent predictor that increased the risk eightfold independent of age, energy use or perioperative anticoagulation status. The most common reason for conversion was bleeding that obscured vision but not the inability to handle a large gland via an endoscopic approach. Indeed, no case was converted to open prostatectomy. This conversion rate is lower than in a previous randomized, controlled trial comparing PVP with the HPS 120 W system to HoLEP in patients with a prostate greater than 60 gm.4 In that series 22% of PVP cases were converted to TURP or HoLEP intraoperatively because of bleeding or inadequate tissue removal. In this later study the high conversion rate was likely due to the aggressive surgical vapo-resection technique, which was possibly used to compensate for the lesser tissue ablation efficacy of the previous generation HPS 120 W. Nevertheless, although the removal efficiency of tissue ablation may be enhanced by the increased XPS-180W energy, bleeding or capsular perforation is still more likely in patients with a larger prostate. Therefore,
Table 3. Operative parameters overall and by PV subgroup Periop Parameters
Median Overall (IQR)/No. Pts
Total operative time (mins) Laser time (mins) Energy (kJ) Energy/PV (kJ/cc) No. fibers
55 (40)/1,043 29 (24)/1,040 226.4 (224)/1,048 3.59 (2.37)/1,012 1 (0)/689
Hospital stay (hrs) Foley catherization (hrs)
24 24
(18)/1,042 (0)/421
* Statistically significantly different vs less than 80 cc.
PV Less Than 80 cc
PV 80 cc or Greater
Median 45 (IQR 25)/658 Median 24 (IQR 16)/758 Median 182.6 (IQR 143)/661 Median 3.8 (IQR 2.6)/661 Median 1.0 (IQR 0), mean SD 1.1 0.4/397 24 (IQR 19)/636 Median 24 (IQR 0), mean SD 26 27/292
Median 80 (IQR 62)/348 Median 45 (IQR 33)/345 Median 371.2 (IQR 261)/351 Median 3.25 (IQR 1.83)/351 Median 1 (IQR 1), mean SD 1.5 1*/256 Median 24 (IQR 18)/346 Median 24 (IQR 24), mean SD 35 30*/129
PV Less than 80 vs 80 cc or Greater p Value (Mann-Whitney test) <0.01 <0.01 <0.01 <0.01 <0.01 0.1 <0.01
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Table 4. Complications % Pts (No./Total No.) Clavien-Dindo Grade
Overall
No. pts I/II: Bleeding, hematuria Urinary tract infection Incontinence (1 pad/day) Dysuria, urgency, frequency (lower urinary tract symptoms) IIIa/IIIb: Bleeding obscuring vision Conversion to TURP Bladder neck/urethral stricture Refractory urinary retention Capsular perforation Blood transfusion
1,126† 18.9 (203/1,072) 9.7 (60/618) 4.9 (34/687) 4.8 (43/895) 14.3 (111/776) 13.0 (146/980) 3.0 (19/636) 3.1 (23/742) 4.2 (31/746) 7.4 (74/999) 0.6 (4/635) 0.0 (0/723)
PV Less Than 80 cc 739 19.1 8.3 4.9 4.8 16.1
PV 80 cc or Greater
p Value*
(133/698) (35/421) (23/471) (28/579) (77/479)
387 18.7 12.7 5.1 4.7 11.4
(70/374) (25/197) (11/216) (15/316) (34/297)
e 0.893 0.08 0.90 0.95 0.07
11.4 (84/739) 2.1 (9/422) 0.6 (3/502) 3.9 (20/508) 7.4 (48/647) 0.5 (2/423) 0.0 (0/490)
16.0 4.7 8.4 4.6 7.4 0.9 0.0
(62/387) (10/214) (20/237) (11/238) (26/352) (2/212) (0/140)
0.027 0.07 <0.01 0.66 0.98 0.48 e
* Chi-square or Fisher test, or t-test. † Patients with TRUS data.
laser surgical management of a gland greater than 80 cc warrants an experienced endoscopic surgeon with established GreenLight laser expertise. A decrease in PSA can serve as a surrogate marker for adenoma removal.21 In the current study the PSA reduction ranged from 42% to 67%. Interestingly the reduction was less in the larger prostate group at all end points, including at 24 months when the median change was 48% vs 65% (p <0.01). This observation may be explained by the lesser energy density delivered in the larger prostate group (3.25 vs 3.8 kJ/cc, p <0.01). It may suggest that larger prostates have a tendency to be treated less optimally. Prostate size reduction was examined in the 322 patients in whom PV was measured by TRUS 6 to 12 weeks after the procedure and compared to preoperative TRUS results. Interestingly the PV change expressed as a percent of the reduction was equivalent between the prostate groups, supporting PVP as a size independent procedure. However, prostate size assessed postoperatively may be inaccurate because of edema and remodeling, making measurements prone to operator bias. Using the previous generation GreenLight HPS 120 W others reported an 11% re-treatment rate during 36 months in patients with a prostate greater than 80 cc.1,22 In a previous study also using the HPS system we observed a 9% re-treatment rate at 12 months in patients with preoperative TRUS greater than 100 cc.12,22 In the current study the re-treatment rates were significantly lower than previously reported, including 0.9% (4 of 462 cases) at 12 months and 1.2% (5 of 411) at 24 months. Although there was substantial loss at followup, these findings are notable when considering previously reported re-treatment rates. Re-treated patients had an average prostate size of almost 120 cc compared to 70 cc in those without
re-treatment. Interestingly the average energy initially used in patients who later required retreatment was 2.1 kJ/cc compared to 4.4 kJ/cc. Similarly the PSA reduction was less in the retreated group (32.2% vs 54%) at 6 months and an increase in PSA was observed at 12 months in the re-treated group, that is a median PSA of 5.5 vs 4.8 ng/ml at baseline. This association between treatment energy density and PSA was already suggested due to a significant correlation between PSA re-ascension after 6 months in patients treated with less than 3 kJ/cc.22 Therefore, in the current study it is likely that a proportion of patients who underwent re-intervention were not adequately treated with appropriate tissue removal. This is reflected in the lesser energy density received during primary treatment and the PSA level at 6 months. Table 5. Multivariable regression analysis of select grade III complications OR (95% CI) Conversion to TURP* Age 1.029 TRUS PV (less than 80 vs 80 cc or greater) 8.255 Laser: Time 1.069 Energy 1.000 Periop anticoagulation 1.213 Capsular penetration Age 1.019 TRUS PV (less than 80 vs 80 cc or greater) 1.610 Laser: Time 1.000 Energy 1.002 Periop anticoagulation 2.341 Bleeding obscuring vision Age 1.029 TRUS PV (less than 80 vs 80 cc or greater) 2.131 Laser: Time 0.979 Energy 1.002 Periop anticoagulation 0.922
p Value
(0.977e1.084) (2.273e29.980)
0.27 <0.01
(1.024e1.116) (0.995e1.006) (0.632e2.327)
<0.01 0.89 0.56
(0.907e1.144) (0.195e13.313)
0.75 0.66
(0.927e1.078) (0.995e1.010) (0.201e27.300)
0.99 0.57 0.5
(0.975e1.085) (0.754e6.023)
0.3 0.15
(0.939e1.021) (0.999e1.006) (0.195e4.368)
0.32 0.22 0.91
* Independently predicted only by PV greater than 80 cc and laser time.
Baseline (cc) Less Than 80
80 or Greater
I-PSS: Mean (95% CI) 21.5 (20.9e22.1) 23.1 (22.1e24.1) Median (IQR) 21 (10) 24 (13) Median change (IQR) Not applicable No. pts 645 308 QOL: Mean (95% CI) 4.48 (4.4e4.6) 4.69 (4.5e4.8) Median (IQR) 5 (1) 5 (2) Median change Not applicable (IQR) No. pts 651 328 Qmax (ml/sec): Mean (95% CI) 6.9 (6.7e7.2) 5.7 (5.2e6.1) Median (IQR) 6.8 (5) 5.0 (5) Median change Not applicable (IQR) No. pts 625 309 PVR (ml): Mean (95% CI) 219.2 (200.8e237.5) 271.8 (245.3e298.3) Median (IQR) 150 (269) 211 (378) % Change Not applicable No. pts 613 290 PSA (ng/ml): Mean (95% CI) 3.5 (3.2e3.9) 6.0 (5.4e6.7) Median (IQR) 2.4 (3) 4.6 (4) % Change Not applicable No. pts 537 253
6 Mos (cc) p Value* <0.01 <0.01
0.3 0.1
Less Than 80 7.2 6.0 17 331
(6.7e7.7) 6.7 (5) 6.0 (10) 19 177
1.36 (1.2e1.5) 1.0 (2) 3 (2) 336
<0.01 <0.01
0.03 0.03
<0.01 <0.01
80 or Greater (6.1e7.4) (5) (13)
1.25 (1.05e1.45) 1.0 (2) 4 (2)
12 Mos (cc) p Value* 0.3 0.5 0.1 0.4 0.1 0.08
177
Less Than 80 6.7 5 17 289
(5.7e7.7) (5) (9)
1.35 (0.87e1.82) 1 (2) 3 (1) 295
17.6 (16.9e18.3) 16.9 (15.9e17.9) 18 (6) 18 (9) 12 (8) 13 (9)
0.25 0.4 0.1
80 or Greater 5.2 4 19 153
24 Mos (cc) p Value*
(4.6e5.85) (4) (16)
0.04 0.01 0.1
0.91 (0.76e1.06) 1 (1) 4 (2.75)
0.2 0.1 0.06
154
Less Than 80 6.1 5 17 139
1.18 (0.96e1.39) 1 (2) 3 (1)
0.9 0.9 0.2
170
278
37.7 (29.5e46.0) 12 (42) 95.50 289
47 (33.6e60.4) 0.2 15 (47) 0.1 93.20 0.4 159 448
33.1 (25.2e41.0) 49.6 (33.1e63.1) 0.03 32.2 10 (29) 14 (51) 0.05 15 93.20 92.00 0.50 93.80 258 137 395 121
* Medians and means compared by Mann-Whitney U test and Student t-test, respectively.
(3.2e5.1) (4)
<0.01 <0.01 <0.01
1.5 1 61.00 226
148
(1.3e1.8) (1)
4.0 2.5 50.00 108
<0.01 <0.01 <0.01
0.3 0.13 0.14
0.91 (0.68e1.13) 1 (1) 4 (2.75)
0.13 0.1 0.8
64
131
(3.3e4.7) (4)
1.6 0.9 61 104
p Value*
(4.2e6.6) (4) (16)
18.8 (16.3e21.2) 18.3 (16.5e20.2) 19 (7) 19 (8) 12 (9) 12 (8)
328
1.37 (1.1e1.6) 4.2 1 (1) 2.3 66.00 45.00 221 102
(5.4e6.8) 5.4 (4) 4 (9) 19 63
141
17.8 (17.1e18.4) 17.8 (16.8e18.8) 18.2 (6) 18.3 (8) 12 (8) 13.1 (8)
80 or Greater
0.8 0.9 0.3
56 (23e41.6) 58.3 (38e78.6) (34) 24 (66) 93.80 59 (1.1e2.1) (2)
3.4 47 38
0.02 0.03 0.2
(2.1e4.7) <0.01 1.9 (3) <0.01 <0.01
PHOTOSELECTIVE VAPORIZATION FOR BENIGN PROSTATIC HYPERPLASIA
Table 6. I-PSS, QoL, Qmax, PVR and PSA at baseline, and 6, 12 and 24 months between prostates less than 80 vs 80 cc or greater
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To our knowledge the exact amount of energy required to best treat a given prostate is not known. However, we infer from this study that it could be at least 4 kJ/cc. Optimal treatment may be indirectly assessed postoperatively by a reduction of at least 50% in PV as measured by TRUS or by a greater than 50% decrease in PSA at 3 months. The strength of this study is the large number of patients (1,196) included. To our knowledge this is the largest retrospective study of PVP using the GreenLight XPS and the only one to date providing outcome data, including PSA at 2 years. Limitations include the bias introduced by missing data due to its retrospective nature and patient loss during followup. In addition, the heterogeneity in the reporting of complications and the absence of sexual function measurements are regrettable.
A
B
CONCLUSIONS
A, TRUS PV preoperatively (Pre-op) vs 6 to 12 weeks postoperatively (Post-op) in subgroup of 322 patients. Median TRUS change was 55.6% vs 54.8% for PV less than 80 cc (red bars) vs 80 cc or greater (green bars) (p ¼ 0.4). B, median PSA change 3 months postoperatively by time in all 322 patients (all end points vs baseline, PV less than 80 vs 80 cc or greater at baseline and all end points including 24 months p <0.01). At 6, 12 and 24 months median PSA change was 67% vs 46.5%, 61% vs 42% and 65% vs 48%, respectively, for PV less than 80 vs 80 cc or greater (each p <0.01). Blue bars represent values in all prostates.
XPS-180W is safe and effective, and can provide durable amelioration of symptoms at 2 years, including in men with a prostate 80 cc or greater. Nevertheless, patients with a larger prostate may be more challenging, as reflected by the higher rate of conversion to TURP. Because of the higher risk of TURP, patients with a prostate greater than 80 cc who undergo conversion should be treated by experienced GreenLight laser surgeons. Preoperative evaluation by TRUS sizing is strongly recommended since it has direct implications for operative parameters and potential complications. Although to our knowledge the optimal energy use is unknown, the current data suggest that applying at least 4 kJ per prostate cc is necessary to achieve sufficient adenoma removal for durable long-term outcomes. Optimal treatment aims may include a 50% or greater decrease in PSA and/or PV postoperatively as a potential predictor of durable longterm outcomes.
REFERENCES 1. Hueber PA, Liberman D, Ben-Zvi T et al: 180 W vs 120 W lithium triborate photoselective vaporization of the prostate for benign prostatic hyperplasia: a global, multicenter comparative analysis of perioperative treatment parameters. Urology 2013; 82: 1108.
transurethral resection of the prostate for treatment of benign prostatic hyperplasia: a randomized clinical trial with midterm follow-up. Eur Urol 2010; 58: 349.
2. Ben-Zvi T, Hueber PA, Liberman D et al: GreenLight XPS 180W vs HPS 120W laser therapy for benign prostate hyperplasia: a prospective comparative analysis after 200 cases in a single-center study. Urology 2013; 81: 853.
4. Hueber PA, Ben-Zvi T, Liberman D et al: Mid term outcomes of initial 250 case experience with GreenLight 120W-HPS photoselective vaporization prostatectomy for benign prostate hyperplasia: comparison of prostate volumes < 60 cc, 60 cc-100 cc and > 100 cc. Can J Urol 2012; 19: 6395.
3. Al-Ansari A, Younes N, Sampige VP et al: GreenLight HPS 120-W laser vaporization versus
5. Tasci AI, Ilbey YO, Luleci H et al: 120-W GreenLight laser photoselective vaporization of
prostate for benign prostatic hyperplasia: midterm outcomes. Urology 2011; 78: 134. 6. McVary KT, Roehrborn CG, Avins AL et al: Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol 2011; 185: 1793. 7. Madersbacher S, Alivizatos G, Nordling J et al: EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH guidelines). Eur Urol 2004; 46: 547.
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8. Nickel JC, Herschorn S, Corcos J et al: Canadian guidelines for the management of benign prostatic hyperplasia. Can J Urol 2005; 12: 2677. 9. Zorn KC and Liberman D: GreenLight 180W XPS photovaporization of the prostate: how I do it. Can J Urol 2011; 18: 5918. 10. Muir G, Gomez Sancha F, Bachmann A et al: Techniques and training with GreenLight HPS 120-W laser therapy of the prostate: position paper. Eur Urol, suppl., 2008; 7: 361. 11. Woo HH: Photoselective vaporization of the prostate using the 120-W lithium triborate laser in enlarged prostates (>120 cc). BJU Int 2011; 108: 860. 12. Tinmouth WW, Habib E, Kim SC et al: Change in serum prostate specific antigen concentration after holmium laser enucleation of the prostate: a marker for completeness of adenoma resection? J Endourol 2005; 19: 550. 13. Gu X, Vricella GJ, Spaliviero M et al: Does size really matter? The impact of prostate volume on the efficacy and safety of GreenLight HPS laser photoselective vaporization of the prostate. J Endourol 2012; 26: 525.
14. Bachmann A, Muir GH, Collins EJ et al: 180-W XPS GreenLight laser therapy for benign prostate hyperplasia: early safety, efficacy, and perioperative outcome after 201 procedures. Eur Urol 2012; 61: 600. 15. Misrai V, Faron M, Elman B et al: XPS Greenlight photoselective vaporization for benign prostatic hyperplasia: analysis of the learning curve and contribution of transrectal ultrasound monitoring. Prog Urol 2013; 23: 869.
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obstruction: 12-months results of the GOLIATH study. J Urol 2015; 193: 570. 19. Bachmann A, Tubaro A, Barber N et al: 180-W XPS GreenLight laser vaporisation versus transurethral resection of the prostate for the treatment of benign prostatic obstruction: 6-month safety and efficacy results of a European Multicentre Randomised Trialdthe GOLIATH study. Eur Urol 2014; 65: 931.
16. Emara AM and Barber NJ: The continuous evolution of the Greenlight laser; the XPS generator and the MoXy laser fiber, expanding the indications for photoselective vaporization of the prostate. J Endourol 2014; 28: 73.
20. Lukacs B, Loeffler J, Bruyere F et al: Photoselective vaporization of the prostate with GreenLight 120-W laser compared with monopolar transurethral resection of the prostate: a multicenter randomized controlled trial. Eur Urol 2012; 61: 1165.
17. Campbell NA, Chung AS, Yoon PD et al: Early experience photoselective vaporisation of the prostate using the 180W lithium triborate and comparison with the 120W lithium triborate laser. Prostate Int 2013; 1: 42.
21. Elshal AM, Elmansy HM and Elhilali MM: Feasibility of holmium laser enucleation of the prostate (HoLEP) for recurrent/residual benign prostatic hyperplasia (BPH). BJU Int 2012; 110: E845.
18. Bachmann A, Tubaro A, Barber N et al: A European 180-W GreenLight-XPS laser vaporization and transurethral resection of the prostate for the treatment of benign prostatic
22. Lebdai S, Prezelin Y, Pereira H et al: Prostate-specific antigen evolution after photoselective vaporization of the prostate. J Endourol 2014; 28: 347.
Abbreviations and Acronyms BPH ¼ benign prostatic hyperplasia HoLEP ¼ holmium laser enucleation of prostate I-PSS ¼ International Prostate Symptom Score PSA ¼ prostate specific antigen PV ¼ prostate volume PVP ¼ photoselective vaporization of prostate PVR ¼ post-void residual urine volume Qmax ¼ maximum urinary flow rate QOL ¼ quality of life TRUS ¼ transrectal ultrasound TURP ¼ transurethral prostate resection XPS-180W ¼ GreenLight XPS 180 W system
Purpose: We evaluated photoselective vaporization of the prostate using the GreenLightÔ XPSÔ 180 W system for benign prostatic hyperplasia treatment in a large multi-institutional cohort at 2 years. We particularly examined safety, outcomes and the re-treatment rate in larger prostates, defined as a prostate volume of 80 cc or greater, to assess the potential of photoselective vaporization of the prostate as a size independent procedure. Materials and Methods: A total of 1,196 patients were treated at 6 international centers in Canada, the United States, France and England. All parameters were collected retrospectively, including complications, I-PSS, maximum urinary flow rate, post-void residual urine, prostate volume, prostate specific antigen and the endoscopic re-intervention rate. Subgroup stratified comparative analysis was performed according to preoperative prostate volume less than 80 vs 80 cc or greater on transrectal ultrasound. Results: Median prostate size was 50 cc in 387 patients and 108 cc in 741 in the prostate volume groups less than 80 and 80 cc or greater, respectively. The rate of conversion to transurethral prostate resection was significantly higher in the 80 cc or greater group than in the less than 80 cc group (8.4% vs 0.6%, p <0.01). I-PSS, quality of life score, maximum urinary flow rate and post-void residual urine were significantly improved compared to baseline at 6, 12 and 24 months of followup without significant differences between the prostate size groups. The re-treatment rate at 2 years reported in 5 of 411 patients was associated with the delivery of decreased energy density (2.1 vs 4.4 kJ/cc) in the group without re-treatment. Accepted for publication March 13, 2015. Study received institutional review board approval. * Financial interest and/or other relationship with American Medical Systems. † Financial interest and/or other relationship with American Medical Systems and Endo. ‡ Financial interest and/or other relationship with Intuitive Surgical. § Correspondence: University of Montreal Hospital Center, University of Montreal, Montreal, Quebec, Canada (e-mail: zorn.chumurology@ gmail.com).
Editor’s Note: This article is the fourth of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 602 and 603.
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0022-5347/15/1942-0462/0 THE JOURNAL OF UROLOGY® Ó 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2015.03.113 Vol. 194, 462-469, August 2015 Printed in U.S.A.
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Conclusions: Photoselective vaporization of the prostate using the XPS 180 W system is safe and efficacious, providing durable improvement in functional outcomes at 2 years independent of prostate size when treated with sufficient energy. Key Words: prostate, prostatic hyperplasia, laser therapy, volatilization, organ size
GREENLIGHT laser PVP as BPH treatment has significantly evolved in the last decade. The third generation XPS laser system introduced in 2010 features an increased laser beam diameter and a maximum power output to 180 W. Investigators reported that XPS-180W shows significantly decreased operative time and fiber use with increased energy delivery efficiency compared to the previous generation HPSÔ 120 W system.1,2 For earlier generations of the GreenLight laser system such as the HPS 120 W the higher re-treatment rate in patients with a prostate greater than 80 cc was attributed to insufficient adenoma removal.3e5 To our knowledge whether this limitation can be palliated using the novel XPS-180W remains to be determined. We prospectively assessed XPS-180W clinical outcomes at 2 years of followup in a large, multicenter, prospectively collected cohort. In particular special attention was given to the safety and durability of outcomes in patients with a large prostate (greater than 80 cc) to assess the potential of GreenLight PVP as a size independent procedure.
PATIENTS AND METHODS Study Population Eligible for study were all men with BPH who underwent Greenlight PVP using XPS-180W from May 2011 to May 2012, as performed by 1 of 7 high volume, experienced surgeons at a total of 6 sites in Canada, the United States, France and the United Kingdom. Excluded from study were patients with known prostate cancer, previous pelvic radiation or known neurological disorders. After receiving institutional board review approval 1,196 patients were identified. Indications for surgery in each country were based on similar criteria established by CUA (Canadian Urological Association), AUA (American Urological Association) and EAU (European Association of Urology) guidelines on BPH management.2
Surgical Procedure All patients underwent PVP as previously described using XPS-180W.6e8 Procedures were done according to published IGLU (International GreenLight User) guidelines and incorporated the technique and experience of the operating surgeon.9 Procedures were performed with the patient under general or spinal anesthesia and preoperative antibiotic prophylaxis was administered according to local guidelines. All surgeons were well beyond the learning curve for surgical technique and for several years
had used various previous generations of GreenLight systems (greater than 200 PVP procedures). In all cases a 23Fr continuous flow cystoscope with a 30-degree lens was used while being irrigated with room temperature saline. A working space was typically created initially at a power of 80 W. For the remainder of the procedure power was increased to 180 W adjusted in steps of 10 to 20 W. For coagulation the TruCoagÔ feature pulse was used, modulated at 12 Hz and 5 to 40 W. The MoXyÔ fibers were manufactured with a maximum energy delivery capacity of 650 kJ per unit. These fibers also featured a cooling system and a protective cap at the tip to minimize fiber devitrification. According to the manufacturer these features were designed to improve fiber durability and preserve optimal energy delivery on prostate tissue during the procedure.10 The intended surgical end point was tissue ablation down to the surgical capsule from bladder neck to verumontanum circumferentially to create the same defect as complete TURP.
Primary Outcomes Safety was evaluated by measuring the adverse events related to primary treatment. Efficacy was assessed by quantitative uroflowmetry parameter improvements as well as the subjective I-PSS score, including the QOL score, 6, 12 and 24 months after XPS-180W treatment. In addition, PSA reduction served as a surrogate marker of tissue removal.9 In 322 patients prostate size reduction was also determined by subtracting postoperative TRUS size at 3 months (6 to 12 weeks) from preoperative TRUS size. The endoscopic re-treatment rate was assessed 1 and 2 years after treatment. Subgroup comparative analysis was performed in patients with a prostate less than 80 vs 80 cc or greater as determined by preoperative TRUS PV. The effect of prostate size on safety efficacy and the re-treatment rate was examined.
Assessment We retrospectively collected preoperative data, including patient age and PV on TRUS, along with operative parameters, including total operative time, laser time, total energy use and number of fibers. Energy density was defined as the ratio of the amount of energy applied during treatment divided by prostate size defined according to preoperative TRUS measurements.
Statistical Analysis Parameters such as prostate size, energy and PSA were not normally distributed. Accordingly data are shown as the median and IQR. Because variables such as I-PSS or age were continuous data, they are shown as the mean and 95% CI. To compare the 2 groups of patients with a
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prostate less than 80 vs 80 cc or greater at baseline and at each followup end point the Mann-Whiney U test was used for median comparisons while the Student t-test was used for mean comparisons. To compare postoperative outcomes to baseline data the paired t-test or Wilcoxon test was done correspondingly. For categorical data the chi-square or Fisher test was used. Two-sided p <0.05 was considered statistically significant.
RESULTS A total of 1,196 patients underwent transurethral PVP. Table 1 lists institutions, locations and surgeons. Table 2 lists patient baseline characteristics. As defined by TRUS overall preoperative PV (median 61.4 cc) was only available in 1,128 patients with a median age of 70 years at surgery. Patient demographics were further stratified by PV less than 80 vs 80 cc or greater (table 2). Patients with a larger prostate were older with more severe lower urinary tract symptoms. They were more likely to be treated with BPH medication, including a-blockers and 5a-reductase inhibitors. Table 3 lists operative parameters. Overall procedure duration and energy use increased according to prostate size (less than 80 vs 80 cc or greater), corresponding to an energy density of 3.8 vs 3.25 kJ per prostate gm, respectively (p <0.01). The median number of fibers was generally 1 per case but this was slightly higher in the large prostate group (p <0.01). Hospital stay was 24 hours regardless of prostate size but mean catheterization duration was slightly longer, including 34 and 26 hours in the larger and smaller prostate groups, respectively (p <0.01). Table 4 lists the number of patients with at least 1 complication by Clavien-Dindo grade. Most complications were equivalent in the 2 groups (p >0.05). However, the incidence of conversion to TURP was significantly greater in the 80 cc or greater group compared to the less than 80 cc group (8.4% vs 0.6%, p <0.01). Multivariable regression analysis revealed that prostate size greater than 80 cc and lasing time were significant independent predictors of capsular perforation (table 5). I-PSS and QOL scores were significantly improved compared to baseline at 6, 12 and 24 Table 1. Distribution of 1,196 patients among institutions, surgeons and locations Institution University of Montreal, Montreal, Canada Columbia University, New York, New York Cornell University, New York, New York Frimley Park National Health Service, Frimley, United Kingdom Clinique Pasteur, Toulouse, France Hackensack University, Hackensack, New Jersey
No. Pts (%) 320 108 320 130
(27) (9) (27) (11)
231 (19) 85 (7)
Surgeons KCZ MR AET, BC NJB VM RM
months of followup without a significant difference between the prostate size groups in the change in I-PSS or QOL (paired test p <0.01, table 6). At 24 months for PV less than 80 vs 80 cc or greater the median I-PSS change was 17 vs 19 (p ¼ 0.14) and the median QOL score change was 3 vs 4 (p ¼ 0.8). Similarly median Qmax was increased at all endpoints compared to baseline (paired test p <0.01). At 24 months median Qmax was 19 ml per second for PV less than 80 and 80 cc or greater (p ¼ 0.9). PVR was improved in all patients regardless of prostate size at all endpoints compared to baseline (paired test p <0.01). The improvements were maintained up to 24 months (p ¼ 0.03, table 6). At 24 months the PVR change was 93.8% for PV less than 80 and 80 cc or greater (p ¼ 0.2). Median PSA was significantly higher in the larger prostate group at baseline and at all end points. The median PSA reduction expressed as a percent of the decrease was less in the 80 cc or greater prostate group at 6, 12 and 24 months (p <0.01). In a subset of 322 patients the PV change measured by the size difference between preoperative TRUS at baseline and TRUS measured 6 to 12 weeks postoperatively was also decreased more than 50% (part A of figure). However, this reduction was equivalent regardless of preoperative prostate size (53.8% vs 52.5% p ¼ 0.21). Similarly the PSA reduction at 3 months was equivalent between prostate size groups in this patient subset (52.4% vs 54.3%, p ¼ 0.8, part B of figure). The re-treatment rate at 12 and 24 months was less than 1% (4 of 462 patients) and 1.2% (5 of 411), respectively. Interestingly mean PV in the re-treated group was almost 120 cc, which was significantly larger than in the group without re-treatment. However, the energy delivered per prostate was lower in the re-treated group than in the group without re-treatment (2.1 vs 4.4 kJ/cc, p <0.01).
DISCUSSION In patients with a prostate greater than 80 to 100 cc who need BPH surgical treatment HoLEP is considered the laser therapy of choice as the only size independent procedure with demonstrated long-term functional outcomes and a true alternative to open prostatectomy. Growing evidence may also support the role of GreenLight PVP in the treatment of large prostates. Safety and short-term efficacy were observed in patients with a prostate up to 300 cc.11,12 However, in terms of prostatic tissue removal PVP is still considered less efficient than HoLEP or open prostatectomy.1,2,11,13 To date there are limited clinical data on PVP using the latest XPS system.2,14e17 The recent
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Table 2. Baseline characteristics overall and by PV subgroup PV (cc) Overall Median baseline (IQR)/No. pts:* Preop TRUS PV (cc) I-PSS QOL Qmax (ml/sec) PVR (ml) PSA (ng/ml) Age No. subgroup/total No. (%):† Acute urinary retention þ catheter Median lobe a-Blocker 5a-Reductase inhibitor ASAÒ physical status Clopidogrel Warfarin
Less Than 80
80 or Greater
p Value
61.4 (46)/1,128 22 (11)/996 5 (1)/1,021 6 (5)/970 151 (304)/945 3.0 (3.94)/791 70 (13)/1,190
50 (22)/741 21 (10)/645 5 (1)/651 6.8 (5)/625 150 (269)/613 2.4 (3.12)/537 69 (14)/740
108 (50)/387 24 (13)/308 5 (2)/328 5.0 (5)/309 211 (378)/290 4.6 (4.6)/253 71.6 (12)/383
<0.01 <0.01 0.01 <0.01 <0.01 <0.01 <0.01
222/1,196 220/508 853/1,195 589/1,189 326/1,196 53/1,196 76/1,196
136/739 126/739 557/739 318/739 202/739 33/739 47/739
86/387 93/387 265/387 228/387 103/387 16/387 25/387
0.08 <0.01 0.03 <0.01 0.7 0.8 0.9
(18.6) (43.3) (71.4) (49.5) (27.3) (4.4) (6.4)
(18.4) (17.1) (75.4) (43.0) (27.3) (4.5) (6.4)
(22.2) (24.0) (68.5) (58.9) (26.6) (4.1) (6.5)
* Mann-Whitney test p values. † Chi-square or Fisher test p values and total number of patients may not equal sum of subgroups due to loss at followup.
European randomized, controlled GOLIATH trial comparing XPS to TURP in men with BPH showed that XPS was not inferior to TURP based on I-PSS assessment at 6 and 12 months.18 However, this trial only included 136 patients treated with XPS and they had a relatively small prostate (mean PV 48.6 cc) while patients with a prostate greater than 100 cc were excluded.19,20 In the current study 387 patients with a prostate of 80 cc or greater were successfully treated with XPS-180W. As shown, energy use in kJ as a measured operative parameter was associated with preoperative PV in cc and the required delivered energy density ranged between 3 and 4 kJ/cc. In terms of efficacy, despite differences at baseline the improvements in I-PSS, QOL score, Qmax and PVR were equivalent between the groups at 24 months, confirming durable improvements in outcomes regardless of prostate size. In terms of safety, most complications were Clavien-Dindo grade I/II with no significant difference between the size groups. However, the incidence of conversion to TURP was significantly greater in the larger prostate group (8% for 80 cc
or greater vs 0.6% for less than 80 cc, p <0.01). Prostate size appeared to be an independent predictor that increased the risk eightfold independent of age, energy use or perioperative anticoagulation status. The most common reason for conversion was bleeding that obscured vision but not the inability to handle a large gland via an endoscopic approach. Indeed, no case was converted to open prostatectomy. This conversion rate is lower than in a previous randomized, controlled trial comparing PVP with the HPS 120 W system to HoLEP in patients with a prostate greater than 60 gm.4 In that series 22% of PVP cases were converted to TURP or HoLEP intraoperatively because of bleeding or inadequate tissue removal. In this later study the high conversion rate was likely due to the aggressive surgical vapo-resection technique, which was possibly used to compensate for the lesser tissue ablation efficacy of the previous generation HPS 120 W. Nevertheless, although the removal efficiency of tissue ablation may be enhanced by the increased XPS-180W energy, bleeding or capsular perforation is still more likely in patients with a larger prostate. Therefore,
Table 3. Operative parameters overall and by PV subgroup Periop Parameters
Median Overall (IQR)/No. Pts
Total operative time (mins) Laser time (mins) Energy (kJ) Energy/PV (kJ/cc) No. fibers
55 (40)/1,043 29 (24)/1,040 226.4 (224)/1,048 3.59 (2.37)/1,012 1 (0)/689
Hospital stay (hrs) Foley catherization (hrs)
24 24
(18)/1,042 (0)/421
* Statistically significantly different vs less than 80 cc.
PV Less Than 80 cc
PV 80 cc or Greater
Median 45 (IQR 25)/658 Median 24 (IQR 16)/758 Median 182.6 (IQR 143)/661 Median 3.8 (IQR 2.6)/661 Median 1.0 (IQR 0), mean SD 1.1 0.4/397 24 (IQR 19)/636 Median 24 (IQR 0), mean SD 26 27/292
Median 80 (IQR 62)/348 Median 45 (IQR 33)/345 Median 371.2 (IQR 261)/351 Median 3.25 (IQR 1.83)/351 Median 1 (IQR 1), mean SD 1.5 1*/256 Median 24 (IQR 18)/346 Median 24 (IQR 24), mean SD 35 30*/129
PV Less than 80 vs 80 cc or Greater p Value (Mann-Whitney test) <0.01 <0.01 <0.01 <0.01 <0.01 0.1 <0.01
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466
Table 4. Complications % Pts (No./Total No.) Clavien-Dindo Grade
Overall
No. pts I/II: Bleeding, hematuria Urinary tract infection Incontinence (1 pad/day) Dysuria, urgency, frequency (lower urinary tract symptoms) IIIa/IIIb: Bleeding obscuring vision Conversion to TURP Bladder neck/urethral stricture Refractory urinary retention Capsular perforation Blood transfusion
1,126† 18.9 (203/1,072) 9.7 (60/618) 4.9 (34/687) 4.8 (43/895) 14.3 (111/776) 13.0 (146/980) 3.0 (19/636) 3.1 (23/742) 4.2 (31/746) 7.4 (74/999) 0.6 (4/635) 0.0 (0/723)
PV Less Than 80 cc 739 19.1 8.3 4.9 4.8 16.1
PV 80 cc or Greater
p Value*
(133/698) (35/421) (23/471) (28/579) (77/479)
387 18.7 12.7 5.1 4.7 11.4
(70/374) (25/197) (11/216) (15/316) (34/297)
e 0.893 0.08 0.90 0.95 0.07
11.4 (84/739) 2.1 (9/422) 0.6 (3/502) 3.9 (20/508) 7.4 (48/647) 0.5 (2/423) 0.0 (0/490)
16.0 4.7 8.4 4.6 7.4 0.9 0.0
(62/387) (10/214) (20/237) (11/238) (26/352) (2/212) (0/140)
0.027 0.07 <0.01 0.66 0.98 0.48 e
* Chi-square or Fisher test, or t-test. † Patients with TRUS data.
laser surgical management of a gland greater than 80 cc warrants an experienced endoscopic surgeon with established GreenLight laser expertise. A decrease in PSA can serve as a surrogate marker for adenoma removal.21 In the current study the PSA reduction ranged from 42% to 67%. Interestingly the reduction was less in the larger prostate group at all end points, including at 24 months when the median change was 48% vs 65% (p <0.01). This observation may be explained by the lesser energy density delivered in the larger prostate group (3.25 vs 3.8 kJ/cc, p <0.01). It may suggest that larger prostates have a tendency to be treated less optimally. Prostate size reduction was examined in the 322 patients in whom PV was measured by TRUS 6 to 12 weeks after the procedure and compared to preoperative TRUS results. Interestingly the PV change expressed as a percent of the reduction was equivalent between the prostate groups, supporting PVP as a size independent procedure. However, prostate size assessed postoperatively may be inaccurate because of edema and remodeling, making measurements prone to operator bias. Using the previous generation GreenLight HPS 120 W others reported an 11% re-treatment rate during 36 months in patients with a prostate greater than 80 cc.1,22 In a previous study also using the HPS system we observed a 9% re-treatment rate at 12 months in patients with preoperative TRUS greater than 100 cc.12,22 In the current study the re-treatment rates were significantly lower than previously reported, including 0.9% (4 of 462 cases) at 12 months and 1.2% (5 of 411) at 24 months. Although there was substantial loss at followup, these findings are notable when considering previously reported re-treatment rates. Re-treated patients had an average prostate size of almost 120 cc compared to 70 cc in those without
re-treatment. Interestingly the average energy initially used in patients who later required retreatment was 2.1 kJ/cc compared to 4.4 kJ/cc. Similarly the PSA reduction was less in the retreated group (32.2% vs 54%) at 6 months and an increase in PSA was observed at 12 months in the re-treated group, that is a median PSA of 5.5 vs 4.8 ng/ml at baseline. This association between treatment energy density and PSA was already suggested due to a significant correlation between PSA re-ascension after 6 months in patients treated with less than 3 kJ/cc.22 Therefore, in the current study it is likely that a proportion of patients who underwent re-intervention were not adequately treated with appropriate tissue removal. This is reflected in the lesser energy density received during primary treatment and the PSA level at 6 months. Table 5. Multivariable regression analysis of select grade III complications OR (95% CI) Conversion to TURP* Age 1.029 TRUS PV (less than 80 vs 80 cc or greater) 8.255 Laser: Time 1.069 Energy 1.000 Periop anticoagulation 1.213 Capsular penetration Age 1.019 TRUS PV (less than 80 vs 80 cc or greater) 1.610 Laser: Time 1.000 Energy 1.002 Periop anticoagulation 2.341 Bleeding obscuring vision Age 1.029 TRUS PV (less than 80 vs 80 cc or greater) 2.131 Laser: Time 0.979 Energy 1.002 Periop anticoagulation 0.922
p Value
(0.977e1.084) (2.273e29.980)
0.27 <0.01
(1.024e1.116) (0.995e1.006) (0.632e2.327)
<0.01 0.89 0.56
(0.907e1.144) (0.195e13.313)
0.75 0.66
(0.927e1.078) (0.995e1.010) (0.201e27.300)
0.99 0.57 0.5
(0.975e1.085) (0.754e6.023)
0.3 0.15
(0.939e1.021) (0.999e1.006) (0.195e4.368)
0.32 0.22 0.91
* Independently predicted only by PV greater than 80 cc and laser time.
Baseline (cc) Less Than 80
80 or Greater
I-PSS: Mean (95% CI) 21.5 (20.9e22.1) 23.1 (22.1e24.1) Median (IQR) 21 (10) 24 (13) Median change (IQR) Not applicable No. pts 645 308 QOL: Mean (95% CI) 4.48 (4.4e4.6) 4.69 (4.5e4.8) Median (IQR) 5 (1) 5 (2) Median change Not applicable (IQR) No. pts 651 328 Qmax (ml/sec): Mean (95% CI) 6.9 (6.7e7.2) 5.7 (5.2e6.1) Median (IQR) 6.8 (5) 5.0 (5) Median change Not applicable (IQR) No. pts 625 309 PVR (ml): Mean (95% CI) 219.2 (200.8e237.5) 271.8 (245.3e298.3) Median (IQR) 150 (269) 211 (378) % Change Not applicable No. pts 613 290 PSA (ng/ml): Mean (95% CI) 3.5 (3.2e3.9) 6.0 (5.4e6.7) Median (IQR) 2.4 (3) 4.6 (4) % Change Not applicable No. pts 537 253
6 Mos (cc) p Value* <0.01 <0.01
0.3 0.1
Less Than 80 7.2 6.0 17 331
(6.7e7.7) 6.7 (5) 6.0 (10) 19 177
1.36 (1.2e1.5) 1.0 (2) 3 (2) 336
<0.01 <0.01
0.03 0.03
<0.01 <0.01
80 or Greater (6.1e7.4) (5) (13)
1.25 (1.05e1.45) 1.0 (2) 4 (2)
12 Mos (cc) p Value* 0.3 0.5 0.1 0.4 0.1 0.08
177
Less Than 80 6.7 5 17 289
(5.7e7.7) (5) (9)
1.35 (0.87e1.82) 1 (2) 3 (1) 295
17.6 (16.9e18.3) 16.9 (15.9e17.9) 18 (6) 18 (9) 12 (8) 13 (9)
0.25 0.4 0.1
80 or Greater 5.2 4 19 153
24 Mos (cc) p Value*
(4.6e5.85) (4) (16)
0.04 0.01 0.1
0.91 (0.76e1.06) 1 (1) 4 (2.75)
0.2 0.1 0.06
154
Less Than 80 6.1 5 17 139
1.18 (0.96e1.39) 1 (2) 3 (1)
0.9 0.9 0.2
170
278
37.7 (29.5e46.0) 12 (42) 95.50 289
47 (33.6e60.4) 0.2 15 (47) 0.1 93.20 0.4 159 448
33.1 (25.2e41.0) 49.6 (33.1e63.1) 0.03 32.2 10 (29) 14 (51) 0.05 15 93.20 92.00 0.50 93.80 258 137 395 121
* Medians and means compared by Mann-Whitney U test and Student t-test, respectively.
(3.2e5.1) (4)
<0.01 <0.01 <0.01
1.5 1 61.00 226
148
(1.3e1.8) (1)
4.0 2.5 50.00 108
<0.01 <0.01 <0.01
0.3 0.13 0.14
0.91 (0.68e1.13) 1 (1) 4 (2.75)
0.13 0.1 0.8
64
131
(3.3e4.7) (4)
1.6 0.9 61 104
p Value*
(4.2e6.6) (4) (16)
18.8 (16.3e21.2) 18.3 (16.5e20.2) 19 (7) 19 (8) 12 (9) 12 (8)
328
1.37 (1.1e1.6) 4.2 1 (1) 2.3 66.00 45.00 221 102
(5.4e6.8) 5.4 (4) 4 (9) 19 63
141
17.8 (17.1e18.4) 17.8 (16.8e18.8) 18.2 (6) 18.3 (8) 12 (8) 13.1 (8)
80 or Greater
0.8 0.9 0.3
56 (23e41.6) 58.3 (38e78.6) (34) 24 (66) 93.80 59 (1.1e2.1) (2)
3.4 47 38
0.02 0.03 0.2
(2.1e4.7) <0.01 1.9 (3) <0.01 <0.01
PHOTOSELECTIVE VAPORIZATION FOR BENIGN PROSTATIC HYPERPLASIA
Table 6. I-PSS, QoL, Qmax, PVR and PSA at baseline, and 6, 12 and 24 months between prostates less than 80 vs 80 cc or greater
467
468
PHOTOSELECTIVE VAPORIZATION FOR BENIGN PROSTATIC HYPERPLASIA
To our knowledge the exact amount of energy required to best treat a given prostate is not known. However, we infer from this study that it could be at least 4 kJ/cc. Optimal treatment may be indirectly assessed postoperatively by a reduction of at least 50% in PV as measured by TRUS or by a greater than 50% decrease in PSA at 3 months. The strength of this study is the large number of patients (1,196) included. To our knowledge this is the largest retrospective study of PVP using the GreenLight XPS and the only one to date providing outcome data, including PSA at 2 years. Limitations include the bias introduced by missing data due to its retrospective nature and patient loss during followup. In addition, the heterogeneity in the reporting of complications and the absence of sexual function measurements are regrettable.
A
B
CONCLUSIONS
A, TRUS PV preoperatively (Pre-op) vs 6 to 12 weeks postoperatively (Post-op) in subgroup of 322 patients. Median TRUS change was 55.6% vs 54.8% for PV less than 80 cc (red bars) vs 80 cc or greater (green bars) (p ¼ 0.4). B, median PSA change 3 months postoperatively by time in all 322 patients (all end points vs baseline, PV less than 80 vs 80 cc or greater at baseline and all end points including 24 months p <0.01). At 6, 12 and 24 months median PSA change was 67% vs 46.5%, 61% vs 42% and 65% vs 48%, respectively, for PV less than 80 vs 80 cc or greater (each p <0.01). Blue bars represent values in all prostates.
XPS-180W is safe and effective, and can provide durable amelioration of symptoms at 2 years, including in men with a prostate 80 cc or greater. Nevertheless, patients with a larger prostate may be more challenging, as reflected by the higher rate of conversion to TURP. Because of the higher risk of TURP, patients with a prostate greater than 80 cc who undergo conversion should be treated by experienced GreenLight laser surgeons. Preoperative evaluation by TRUS sizing is strongly recommended since it has direct implications for operative parameters and potential complications. Although to our knowledge the optimal energy use is unknown, the current data suggest that applying at least 4 kJ per prostate cc is necessary to achieve sufficient adenoma removal for durable long-term outcomes. Optimal treatment aims may include a 50% or greater decrease in PSA and/or PV postoperatively as a potential predictor of durable longterm outcomes.
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