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Photoselective Vaporization of the Prostate with GreenLight 120-W Laser Compared with Monopolar Transurethral Resection of the Prostate: A Multicenter Randomized Controlled Trial
EUROPEAN UROLOGY 61 (2012) 1165–1173
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Benign Prostatic Hyperplasia Editorial by Stephan Madersbacher on pp. 1174–1176 of this issue
Photoselective Vaporization of the Prostate with GreenLight 120-W Laser Compared with Monopolar Transurethral Resection of the Prostate: A Multicenter Randomized Controlled Trial Bertrand Lukacs a,*, Joyce Loeffler b, Franck Bruye`re c, Pascal Blanchet d, Albert Gelet e, Patrick Coloby f, Alexandre De la Taille g, Philippe Lemaire h, Jean-Christophe Baron i, Jean-Nicolas Cornu a, Mounir Aout j, Helene Rousseau j, Eric Vicaut j for the REVAPRO study group a
Department of Urology, Tenon Hospital, Assistance publique Hoˆpitaux de Paris; University Paris VI, Paris, France; b Department of Urology, Pasteur Hospital, Nice University, Nice, France; c Department of Urology, University Hospital of Tours, Tours, France; d Department of Urology, Pointe-a`-Pitre University Hospital, Guadeloupe, West French Indies; e Department of Urology, Edouard Herriot Hospital, Lyon, France; f Department of Urology, Rene´ Dubos Hospital, Pontoise, France; g Department of Urology, Henri Mondor Hospital, Assistance publique Hoˆpitaux de Paris; University Paris XII, Cre´teil, France; h Department of Urology, Les Bleuets Clinic, Reims, France; i Department of Urology, Alliance Clinic, Saint Cyr sur Loire, France; j Clinical Research Unit, Lariboisie`re-Fernand
Widal Hospital, Assistance publique Hoˆpitaux de Paris; University Paris Diderot, Paris, France
Article info
Abstract
Article history: Accepted January 31, 2012 Published online ahead of print on February 7, 2012
Background: Evidence supporting the widespread use of GreenLight High Performance System (HPS) 120-W photoselective vaporization of the prostate (PVP) is lacking. Objective: To assess the noninferiority of PVP compared with transurethral resection of the prostate (TURP) on urinary symptoms and the superiority of PVP over TURP on length of hospital stay. Design, setting, and participants: A multicenter randomized controlled trial was conducted. Intervention: Patients underwent monopolar TURP or PVP with the GreenLight HPS 120-W laser. Measurements: International Prostate Symptom Score (IPSS), Euro-QOL questionnaire, uroflowmetry, Danish Prostate Symptom Score Sexual Function Questionnaire, sexual satisfaction, and adverse events were collected at 1, 3, 6, and 12 mo. The two groups were compared using the 95% confidence interval (CI) of median difference for testing noninferiority of the IPSS at 12 mo and the student t test for testing the difference in length of hospital stay. Results and limitations: A total of 139 patients (70 vs 69 men in each group) were randomized. Median IPSS scores at 12-mo follow-up were 5 (interquartile range [IQR]: 3–8) for TURP versus 6 (IQR: 3–9) for PVP, and the 95% CI of the difference of the median was equal to 2 to 3. Because the upper limit of the 95% CI was >2 (the noninferiority margin), the hypothesis of noninferiority could not be considered demonstrated. Median length of stay was significantly shorter in the PVP group than in the TURP group, with a median of 1 (IQR: 1–2) versus 2.5 (IQR: 2–3.5), respectively ( p < 0.0001). Uroflowmetry parameters and complications were comparable in both groups. Sexual outcomes were slightly better in the PVP group without reaching statistical significance.
Keywords: Transurethral resection of the prostate Photovaporization of the prostate Laser Randomized controlled trial
* Corresponding author. Urology Department, Tenon Hospital, 4 rue de la Chine, 75970 Paris Cedex 20, France. Tel. +01 56 01 64 95; Fax: +01 56 01 73 06. E-mail address: [email protected] (B. Lukacs). 0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2012.01.052
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Conclusions: The present study failed to demonstrate the noninferiority of 120-W GreenLight PVP versus TURP on prostate symptoms at 1 yr but showed that PVP was associated with a shorter length of stay in the hospital. Trial registration: NCT01043588. # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
1.
Introduction
(1 mo for 5-ARIs). All patients with a prostate-specific antigen (PSA) >4 who were candidates for prostate cancer screening underwent prostatic
Benign prostatic hyperplasia (BPH) is a highly prevalent disease, and its management represents an important economic burden in Western countries [1]. BPH is the major etiology of lower urinary tract symptoms (LUTS) in men >50 yr of age. These symptoms are usually assessed by the International Prostate Symptom Score (IPSS) and associated with a variable degree of bother. In cases of moderate to severely bothersome symptoms, medical treatment is appropriate. Surgical therapy, aiming at relieving obstruction, is indicated after the failure of maximal drug therapy or with complications of the disease [2]. Transurethral resection of the prostate (TURP) remains the reference standard, with which any new surgical innovation should be compared [3]. Photoselective vaporization of the prostate (PVP) by GreenLight laser has been presented as a minimally invasive surgical alternative to TURP, with several advantages such as reduced bleeding complications and short hospital stay [4–6]. However, PVP cannot be yet recommended as a first-line therapy because comparative studies against TURP, especially with the High Performance System (HPS) 120-W power device, are still lacking [3]. Only two monocentric randomized controlled trials (RCTs) focused on urinary parameters have been published with the GreenLight HPS 120-W laser [4,7]. Several issues remain unclear concerning PVP such as postoperative irritative symptoms [8], sexual outcomes, and the absence of pathologic material after the procedure resulting in the missed diagnosis of prostate cancer. Our primary goal was to compare the efficacy of PVP with GreenLight and TURP through a noninferiority hypothesis. The secondary aims were to compare adverse events, sexual outcomes, and quality of life after the two procedures.
2.
Patients and methods
2.1.
Study overview
This multicenter RCT was conducted in nine tertiary reference centers from 2009 to 2011. This study was conducted in accordance with the Good Clinical Practice Guidelines and the Declaration of Helsinki. The protocol was approved by our local institutional review board. All participants gave written informed consent before enrollment. This study was funded by a national grant for medical research (assessment of emerging medical therapies program, [STIC2007], French Ministry of Health).
2.2.
Participants
Patients >50 yr of age presenting LUTS/BPH requiring surgical management were screened to participate. Table 1 details the inclusion and exclusion criteria. If present, a treatment by a1-blockers, phytotherapy, or 5a-reductase inhibitors (5-ARIs) had to be stopped 1 wk before surgery
biopsies that were negative in all cases.
2.3.
Study design and data collection
At baseline and during the four follow-up visits, the usual urinary parameters were assessed: IPSS; bother score (question 8 of the IPSS questionnaire); maximum flow rate (Qmax); postvoid residual (PVR) volume; sexual parameters (Danish Prostate Symptom Score Sexual Function Questionnaire [DAN-PSSsex] and a global sexual satisfaction score between 0 and 6, similar to IPSS question 8; and quality-of-life scores (Euro-QOL questionnaire) (Table 2). A dedicated nonvalidated questionnaire was used to assess symptoms after 1 mo (Fig. 1).
2.4.
Interventions
Patients underwent monopolar TURP or PVP (GreenLight HPS 120-W laser; AMS, Minnetonka, MN, USA). All patients received antibiotic prophylaxis. Each local investigator was the only surgeon who did the procedures. All surgeons had to be well experienced in TURP and PVP before the study began. Perioperative data collected were duration of the procedure, irrigation type and volume, type and size of urinary catheter used, and length of hospital stay. During PVP, the total energy used, number of fibers, and the eventual use of electrical coagulation or resection were also assessed. All patients were discharged without catheter after a PVR control following catheter removal.
Table 1 – Inclusion and exclusion criteria of the REVAPRO study Inclusion criteria - IPSS 12 and bother score 3 (according to IPSS question 8) - Qmax <12 ml/s (associated with a >125-ml void) - Prostate volume between 25 ml and 80 ml - Postvoid residual volume <300 ml - Normal digital rectal examination - PSA <4 ng/ml or negative prostate biopsy if PSA between 4 and 10 ng/ml for patients <75 yr of age or with life expectancy >10 yr Exclusion criteria - Patients with urinary catheter before intervention - Active urinary tract infection - Impaired renal function - Unstable cardiac or pulmonary disease - Bladder disease or neurologic disease affecting bladder function - Altered urinary sphincter function, urethral stricture, bladder neck stenosis, active hematuria, or bladder stones - History of prostate or urethral surgery - Anorectal disease - Anticoagulation therapy that cannot be stopped or replaced without risk for the patient - Antiaggregant therapy that cannot be stopped without risk for the patient - Severe coagulopathy - ASA score >3 - Patient unable to complete questionnaires or having no medical insurance IPSS = International Prostate Symptom Score; Qmax = maximum flow rate; PSA = prostate-specific antigen; ASA = American Society of Anesthesiologists.
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Table 2 – Data collection schedule Visit no. Visit purpose Timing Written informed consent Inclusion/exclusion criteria Complete medical history and ASA score Digital rectal examination IPSS score IPSS bother score (question 8) DAN-PSSsex score Global sexuality score EURO-QOL score Maximum flow rate Postvoid residual volume Ultrasound prostate examination PSA blood testing Adverse events ‘‘One-month questionnaire’’ Perioperative parameters
V3
V4
V5
V6
V7
Inclusion visit
V1
Immediate postoperative visit
Follow-up visit
Follow-up visit
Follow-up visit
Follow-up visit
D 30
Day of discharge
M1 5 d
M3 15 d
M6 15 d
M12 30 d
U U U U U U U U U U U
U U U U U U U U
U U U U U U U U U U U
U U U U U U U U U U U U U
V2
Day of intervention (PVP or TURP) U U
U U
U
U U
U
U
ASA = American Society of Anesthesiologists; IPSS = International Prostate Symptom Score; DAN-PSSsex = Danish Prostate Symptom Score Sexual Function Questionnaire; PVP = photoselective vaporization of the prostate; TURP = transurethral resection of the prostate; PSA = prostate-specific antigen.
2.5.
Outcomes
results on urinary symptoms, with a shorter length of stay for PVP. Hence the main objective of the study was to assess the noninferiority of the IPSS
The primary outcome criteria were the IPSS score at 1 yr and the length of
score at 12 mo combined with the superiority of PVP over TURP on the
hospital stay. Our hypothesis was that PVP and TURP generate similar
hospital stay duration (shorter length of stay for PVP). Secondary outcomes
[(Fig._1)TD$IG]
were other urinary parameters (Qmax, PVR), PSA value, complications, sexual symptoms (DAN-PSSsex), sexual satisfaction, and quality of life (Euro-QOL questionnaire).
2.6.
Sample size
It was determined that taking into account a dropout rate of 15%, we needed to enroll 104 patients in each treatment arm to have a power (1) >90% for demonstrating the noninferiority of PVP versus TURP considering a noninferiority margin equal to 2 points of IPSS, assuming a standard deviation (SD) of 3 points for IPSS distribution in both groups (2) equal to 90% to detect a difference in length of stay of 1 d between the two techniques assuming an SD of 2 d.
2.7.
Randomization
Patients were randomized 1:1 in each group by blocks of four via a centralized computerized system to ensure a good balance of participant characteristics in each group. Randomization was stratified by centers. The randomization group for each patient was given by phone via a call center at the inclusion visit. Patients were not blinded to the surgical treatment.
2.8.
Statistical analysis
The statistical analysis was performed according to the intention-to-treat (ITT) principle. For patients lost to follow-up, data were analyzed with the last observation carried forward method. Results were summarized as the mean plus or minus SD for gaussian variables and the median and interquartile range (IQR) for nongaussian variables. Categorical variables were analyzed with the chi-square test or Fisher exact test as appropriate. Primary quantitative outcome variables were compared with the student t test or the Mann-Whitney U test as appropriate. The noninferiority hypothesis was considered demonstrated if the upper value of the 95% Fig. 1 – One-month questionnaire for urinary tract symptoms after endoscopic surgery of the prostate.
confidence interval (CI) limit of the difference of IPSS at 12 mo in PVP versus TURP was < 2 points. Because the statistical distribution of IPSS
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Table 3 – Baseline characteristics of the 139 patients included in the intention-to-treat evaluation Characteristics
TURP (n = 70)
PVP (n = 69)
Age, yr* 67.6 7.6 (51.2–88.7) Qmax* 7.76 2.64 (2.3–14.7) y PVR 75 (28–126) PSA 2.72 (1.7–4.45) Prostate volume* 50.11 14.73 (20–85) Prostate size <49 ml§ (%) 28 (40) 27 (40.3) Presence of a median lobe§ (%) Preoperative IPSSy 20 (15–23) 8.5 (6.5–11) Preoperative IPSS storage subscore (questions 2, 4, 7)y Preoperative IPSS 10.5 (8–14) storage subscore (questions 1, 3, 5, 6)y Sexual satisfaction scale§ (%) 0 Very satisfied 5 (10.2) 1 Satisfied 14 (28.6) 2 Rather satisfied 7 (14.3) 3 Not satisfied, not 11 (22.4) unsatisfied 4 Rather unsatisfied 5 (10.2) 5 Unsatisfied 3 (6.1) 6 Very unsatisfied 4 (8.2) 6 (0–15) DAN-PSSsex scorey 75 [65–85] Euro QOL global scorey
66.9 7.8 (51.7–88.3) 7.79 2.75 (2–15) 89.5 (30–158.5) 2.41 (1.4–4.2) 50.54 16.53 (20–80) 39 (56.5) 24 (34.8) 22 (17–26) 9 (7–12)
13 (9–16)
9 (15.5) 9 (15.5) 8 (13.8) 11 (19) 5 (8.6) 6 (10.3) 10 (17.2) 6.5 (2–18) 70 [60–80]
TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate; Qmax = maximum flow rate; PVR = postvoid residual; ITT = intention to treat; PSA = prostate-specific antigen; IPSS = International Prostate Symptom Score; DAN-PSSsex = Danish Prostate Symptom Score Sexual Function Questionnaire. * Results are given as mean plus or minus standard deviation (range). § Results are given in number of subjects (percentage). y Results are given as median (interquartile range).
was not gaussian, the difference in median and bootstrap CI was used. As recommended for a noninferiority test, an analysis in per protocol populations (ie, patients without major violations) was also conducted. For the main hypothesis, results were considered significant if both hypotheses (noninferiority of PVP vs TURP regarding IPSS at 1 yr and hospital stay significantly shorter in the PVP group) were satisfied. The p values <0.05 were regarded as significant.
3.
Results
3.1.
Population
because they did not come to the hospital for the operation and one because of a contraindication to anesthesia). For all outcomes, the ITT analysis was then conducted on 136 patients who had at least one complete follow-up evaluation (68 men in both groups). IPSS at 12-mo follow-up was available in 125 patients. Figure 2 presents the flowchart. 3.2.
IPSS values at 12 mo-follow-up were not significantly different between the two groups (5 [3–8] for TURP vs 6 [3–9] for PVP; p = 0.494). The 95% CI of the difference of median IPSS at 12 mo was 2 to 3 (the difference in median was 0 with a 95% CI [2 to 2.5] in the per protocol [PP] population). Because the upper limit of the 95% CI was >2 (the noninferiority margin), the hypothesis of noninferiority could not be considered as demonstrated. Median length of stay was significantly shorter in the PVP group than in the TURP group (1 [1,2] vs 2.5 [2–3.5], respectively; p < 0.0001). Figure 3 shows the evolution of IPSS and Qmax during followup. The results for IPSS variation were not significantly different when stratified in function of prostate volume categorized in function of median or quartiles values or smaller/larger than 70 g (interaction p values were 0.55, 0.59, and 0.38, respectively). The results for stratification by size are listed in Table 4. 3.3.
Secondary efficacy outcomes
Qmax, PVR, PSA, and quality of life evaluated at 1 yr were not significantly different in the two groups (Table 5). DANPSSsex score, DANPSSsex subscores, and global sexual satisfaction were not significantly different in the two groups at last follow-up (Table 6). Evolution between preoperative and postoperative erection, ejaculation, and global sexual satisfaction scores showed a trend for improvement of sexual symptoms in the PVP group (Table 6). When improved and unchanged patients were grouped and compared with worsened patients in both arms, evolution of erection and ejaculation were better in the PVP group ( p = 0.04 and p = 0.04, respectively). 3.4.
A total of 139 men were randomized and described in the baseline data (Table 3). Three patients were not treated (two
Primary outcome
Perioperative data
The median duration of the procedure was longer in the PVP group than in the TURP group (71 [55–95] vs 55 [45–65] min, respectively; p = 0.0001). At the end of the procedure, no
Table 4 – International Prostate Symptom Score variation results stratified by prostate size*
y
TURP PVPy Means difference (95% CI) p value
Prostate weight <49 g
Prostate weight 49 g
Prostate weight 70 g
5.38 (3.27–7.49) 6.34 (4.54–8.14) 0.958 (1.86 to 3.78) 0.4983
6.79 (4.91–8.66) 6.80 (4.49–9.11) 0.014 (2.96 to 2.99) 0.9924
7.94 (4.90–10.97) 6.26 (3.23–9.30) 1.68 (5.98 to 2.63) 0.4228
PVP = photoselective vaporization of the prostate; TURP = transurethral resection of the prostate; CI = confidence interval. Data are presented stratified in two groups according to the overall median value of prostate size (49 g) and for the group of prostates >70 g. y Adjusted mean (95% CI). *
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[(Fig._2)TD$IG]
Assessed for eligibility (n = 142)
Enrollment
Excluded (n = 3) ♦ Not meeting inclusion criteria (n = 3)
Randomized (n = 139)
Allocaon Allocated to TURP (n = 70) -3 received PVP (3 refused randomization result)
Allocated to PVP (n = 69) -3 received TURP (1 refused randomization result, 2 without explanations)
-2 received both TURP and PVP (investigator's error)
-1 received both PVP and TURP (failure of the laser device)
-2 without intervention (1 contraindication to anesthesia and 1 did not come to the hospital)
Follow -Up
-1 without intervention (did not come to the hospital)
Lost to follow-up (n = 5)
Lost to follow-up (n = 9)
- 1 refused to continue to participate in the study; 4 lost to follow-up
- 1 death, 3 refused to continue to participate in the study, 5 lost to follow-up
Analysis Analyzed (n = 70)
Analyzed (n = 69)
Fig. 2 – Study flowchart. Data concerning dropouts were analyzed with the last observation carried forward method. PVP = photoselective vaporization of the prostate; TURP = transurethral resection of the prostate.
difference was noted in the size of the catheter used (between 18F and 22F for all patients), but only 37 patients in the PVP group had a two-way irrigation catheter placed versus 66 patients in the TURP group ( p < 0.0001). Mean plus or minus SD power used during PVP was 256, 4 117.0 kJ (0.334–574), for a median duration of vaporization reaching 43 (38–60) min. In six PVP procedures, a monopolar resector was used for resection and coagulation because of failure of the PVP technique; in all cases, this occurred because of perioperative bleeding without capsule perforation. 3.5.
Complications
Overall, perioperative complication rates (39.7% for TURP vs 26.5% for PVP) were not different in the two groups, except for hematuria (Table 7). One patient had to be reoperated in the PVP group (none in the TURP group). Two patients in the PVP group and one patient in the TURP group were discharged with an indwelling urinary catheter. A questionnaire at 1 mofollow-up did not show any differences between the two groups (Table 8).
Late complication rates were comparable in both groups with 16 patients hospitalized (11 TURP and 5 PVP) because of acute urinary retention (5 TURP, 2 PVP), urinary infection (5 TURP, 1 PVP), or other reasons (1 TURP, 2 PVP). 4.
Discussion
More evidence is needed to support the diffusion of the PVP technique as a first-line alternative to TURP [3]. The present study, as the first multicenter RCT comparing PVP and TURP, offers strong evidence that PVP and TURP efficacy are comparable in relieving symptoms of LUTS/BPH. Like the two other RCTs available in the literature [4,7], IPSS scores were not statistically different between the two groups after 1-yr follow-up. But the absence of a significant difference should not be considered a demonstration of the noninferiority of PVP versus TURP. It is the reason why, in contrast with the two other RCTs, the present study used a noninferiority approach for the IPSS score at 12 mo (combined with a superiority approach regarding hospital length of stay).
[(Fig._3)TD$IG]
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Table 5 – Nonsexual secondary outcomes evaluated during follow-up Data
TURP (n = 68)
PVP (n = 68)
p value
Urinary parameters* Qmax 1 mo 14.9 (11.2–18.1) 16 (10.6–21.9) 0.35 3 mo 15.7 (12–19) 17 (12–23) 0.30 6 mo 17.1 (10.9–21) 16.3 (13.5–20.8) 0.68 12 mo 16.8 (12.1–24.9) 16.7 (12–22.7) 0.71 PVR 1 mo 13 (0–50) 20 (0–45) 0.52 3 mo 15 (0–34) 10 (0–34) 0.66 6 mo 19 (0–38) 10 (0–39.5) 0.46 12 mo 7 (0–32) 0 (0–43) 0.75 1.51 (0.61–2.44) 1.81 (0.87–3.60) 0.10 PSA, ng/ml,* at 1 yr 24.7 (18.5–35) 30 (22–40) 0.09 Prostate volume,* ml, at 1 yr Overall satisfactiony (according to a four-level questionnaire) at 1-yr follow-up (%) Very satisfied 23 (37.1) 28 (44.4) Satisfied 31 (50) 25 (39.7) 0.75 Unsatisfied 7 (11.3) 9 (14.3) Very unsatisfied 1 (1.6) 1 (1.6) 75 (60–85) 77 (69.5–87.5) 0.56 EuroQol global score* TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate; Qmax = maximum flow rate; PVR = postvoid residual; PSA = prostate-specific antigen. * Data are given as median (interquartile range). y Data are given as number (percentage).
Fig. 3 – Box plot graphs showing evolution of the urinary parameters during follow-up (data are given as median and interquartile range). (A) Evolution of International Prostate Symptom Score (IPSS); (B) evolution of maximum flow rate (Qmax) in milliliters per second; (C) evolution of postvoiding residual (PVR) in milliliters. PVP = photoselective vaporization of the prostate; TURP = transurethral resection of the prostate.
This noninferiority approach is the only method that allows the conclusion that the difference between the two methods is not too large to permit the substitution of the old technique (TURP) by the new one (PVP). When considering the results of the present study regarding the noninferiority of IPSS, several aspects should be considered. First, we have chosen a very stringent noninferiority margin (ie, only 2 points of IPSS). Both the recruitment (lower than expected) and the SD of IPSS (larger than expected) increased the width of the 95% CI of IPSS. For these reasons, the upper limit of the 95% CI of the difference in medians (ie, 3 for the ITT population and 2.5 for the PP population) exceeded the 2 points corresponding to the noninferiority margin and thus did not allow us to formally conclude noninferiority, even if the observed differences in median IPSS were very small (ie, equal to 1 in the ITT population and to 0 in the PP population). However, these 95% CI values show that if it exists, the difference between the two methods is not clinically meaningful because their upper limits were lower than 3.1, that is, the limit of patient-perceptible IPSS variation in a clinical setting [7,9]. Qmax and PVR were also comparable in the two groups. Since length of stay was inferior in the PVP group because of a reduced need for postoperative irrigation and catheterization, PVP appears to be a useful alternative to TURP with potential benefits in clinical practice. These results, related to the reduced rate of bleeding complications already reported by others with PVP [10,11] can be explained by the tissular effects of GreenLight laser that lead to an optimal coagulation depth of 3 mm in prostatic tissue [12]. However, several issues have been raised about the potential drawbacks of the PVP technique,
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Table 6 – (a) Results from the Danish Prostate Symptom Score Sexual Function Questionnaire and sexual satisfaction questionnaire at 1-yr follow-up*; (b) evolution of sexual satisfaction*, erection score, and ejaculation score at last follow-up compared with baseline a. Sexual symptoms
TURP group (n = 65)
No. of patients sexually active at 12 mo (%) Total DANPSSsex score Total subscore A (symptoms) Total subscore B (bother) Question 1 Presence of erections (1A) Yes, with a normal rigidity Yes, with a slight reduction in rigidity Yes, with a big reduction in rigidity No, I cannot get an erection Related bother (1B) Not at all A little bit Moderate Very much Question 2 Presence of ejaculations (2A) Yes, with a normal amount of semen Yes, with a slightly reduced amount of semen Yes, with a very reduced amount of semen No ejaculation Related bother (2B) Not at all A little bit Moderate Very much Question 3 Pain/discomfort while ejaculating (3A) No Yes, slight pain/discomfort Yes, moderate pain/discomfort Yes, severe pain/discomfort Related bother (3B) Not at all A little bit Moderate Very much Overall sexual satisfaction score
50 6 3 3
(82) (2–15) (2–4) (1–5)
PVP group (n = 60) 43 5 2 2
(76.8) (1–15) (1–4) (1–5)
p value
0.68 0.56 0.28
17 19 11 3 14 17 8 11 – –
21 13 7 2 13 17 4 9 – –
0.55 0.79
6 14 13 17 18 14 11 7 – –
11 9 10 13 13 13 9 8 – –
0.40 0.90
46 4 0 0 28 12 3 7 – – 2 (1–4)
37 4 2 0 31 6 3 3 – – 2 (1–4)
0.41 0.37
0.42
Total (n = 87)
p value
b. TURP (n = 44)
PVP (n = 43)
Evolution of sexual satisfaction after surgery compared with baseline (%) Improved 15 (34.1) Unchanged 15 (34.1) Worsened 14 (31.8)
TURP (n = 39)
19 (44.2) 18 (41.9) 6 (14)
PVP (n = 39)
Evolution of erection score after surgery compared with baseline Improved 9 (23.1) Unchanged 19 (48.7) Worsened 11 (28.2) Evolution of ejaculation score after surgery compared with baseline Improved 4 (10.3) Unchanged 11 (28.2) Worsened 24 (61.5)
34 (39) 33 (38) 20 (39)
Total (n = 78)
0.14
p value
8 (20.5) 27 (69.2) 4 (10.3)
17 (22) 46 (59) 15 (19)
0.09
5 (12.8) 19 (48.7) 15 (38.5)
9 (12) 30 (38) 39 (50)
0.10
TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate. * Data about sexual satisfaction come from 87 sexually active patients. Data about erection and ejaculation come from 78 patients with valid DAN-PSSsex data before and after the procedure (39 patients in each group). Data are given as numbers (percentages).
especially in regard to transient dysuria and irritative symptoms in the first months after surgery, adverse sexual events [13–16], and the absence of pathologic material with PVP.
In the current study we specifically focused on storage symptoms during the early postoperative period that could have an impact on the short-term clinical benefit of the procedure by generating urinary bother. Because IPSS is not
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Table 7 – Early postoperative side effects* TURP (n = 68) Early postoperative side adverse events Postoperative transfusion 1 (1.5) Infection 3 (4.4) Pain/Bother 7 (10.3) Other complications 5 (7.4) Macroscopic hematuria 21 (30.9) Overall 27 (39.7)
PVP (n = 68)
1 2 7 7 7 18
p value
(1.5) (2.9) (10.3) (10.3) (10.3) (26.5)
1.00 1.00 1.00 0.55 0.003 0.10
TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate. * Data are given as numbers (percentages).
Table 8 – One-month postoperative questionnaire results TURP group (n = 62) Question 1: Pain (%) No 16 (25.8) Mild 19 (30.6) Moderate 23 (37.1) Intense 4 (6.5) Question 2: Hematuria (%) No 11 (17.7) Pink color 34 (54.8) Red blood in urine 10 (16.1) Clots 7 (11.3) Question 3: Urgency (%) No 17 (27.4) Yes, acceptable 21 (33.9) Yes, bothersome 20 (32.3) Yes, intolerable 4 (6.5) Question 4: Incontinence (%) No 39 (62.9) Yes, a few times 15 (24.2) Yes, bothering 4 (6.5) Yes, and I had to wear pads 4 (6.5) Question 5: Stream improvement (%) Improved 54 (87.1) Unchanged 5 (8.1) Diminished 3 (4.8) Dripping 0 (0)
PVP group (n = 67)
p value
16 22 25 4
(23.9) (32.8) (37.3) (6)
0.99
15 30 14 8
(22.4) (44.8) (20.9) (11.9)
0.70
17 24 21 5
(25.4) (35.8) (31.3) (7.5)
0.99
33 19 5 10
(49.3) (28.4) (7.5) (14.9)
0.34
55 5 4 2
(83.3) (7.6) (6.1) (3)
0.79
satisfaction question (similar to IPSS question 8 evaluating the global urinary condition). Our results show that erectile and ejaculatory disorders were not different in the two groups at 1-yr follow-up. However, there was a trend for an improvement of erection, ejaculation, and sexual satisfaction in the PVP arm when 12-mo values were compared with baseline. These results, already suggested for ejaculation [6], still need further investigation. Some authors have stated that a potential drawback of PVP could be the absence of tissue for pathologic material analysis [20]. In the present study, more than simply assessing the number of patients diagnosed with cancerous tissue after TURP, we evaluated the number of patients who underwent a curative treatment of prostate cancer after TURP. This was the case for 2 of 68 patients 1 yr after diagnosis. Only one of them had a normal digital rectal examination and a PSA <4 ng/ml before surgery. Although this study as a prospective RCT meets the highest standards of criteria for evidence, the limited followup (1 yr) does not permit us to draw mid- or long-term conclusions. 5.
TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate.
Conclusions
Although the noninferiority between the two techniques could not be formally demonstrated regarding the preestablished criteria of the present study, PVP seems an acceptable alternative to TURP with close results on LUTS improvement in the short term. PVP is associated with a reduced hospital stay with less postoperative irrigation and hematuria. Postoperative symptoms and complications were similar in both arms. Longer follow-up studies are required to confirm the clinical benefits of this technique for the surgical management of LUTS/BPH. Author contributions: Bertrand Lukacs had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Lukacs, Vicaut, Aout. Acquisition of data: Lukacs, Loeffler, Bruye`re, Blanchet, Gelet, Coloby, De la Taille, Lemaire, Baron Analysis and interpretation of data: Rousseau, Aout, Lukacs, Vicaut, Cornu. Drafting of the manuscript: Cornu, Lukacs.
designed for this purpose and poorly targets the specific symptoms of pain while voiding or urgency, we used a dedicated questionnaire. We found no difference between the two groups (Table 8). Although the subscore of storage symptoms was similar in the two groups at inclusion (Table 3), because this questionnaire was completed at 1 mo and was not diary information, recall bias could influence the results for short-term transient postoperative symptoms. Sexual function after PVP has not been adequately evaluated [14,17], and some have questioned whether this procedure has an impact on erectile function [13]. Here we decided to explore sexuality as a multidimensional variable through the validated DANPSSsex score, assessing both erectile and ejaculatory symptoms as well as bother. Given that the urinary symptoms themselves have been linked to sexual function as a whole [18,19], we added a global sexual
Critical revision of the manuscript for important intellectual content: Loeffler, Bruye`re, Coloby, De la Taille. Statistical analysis: Aout, Vicaut. Obtaining funding: Lukacs, Vicaut. Administrative, technical, or material support: Aout. Supervision: Lukacs. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Franck Bruye`re is a proctor and consultant for AMS. Funding/Support and role of the sponsor: French Ministry of Health supported this study by funding the entire study after approval of the initial protocol (GRANT #STIC2007).
EUROPEAN UROLOGY 61 (2012) 1165–1173
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Platinum Priority – Benign Prostatic Hyperplasia Editorial by Stephan Madersbacher on pp. 1174–1176 of this issue
Photoselective Vaporization of the Prostate with GreenLight 120-W Laser Compared with Monopolar Transurethral Resection of the Prostate: A Multicenter Randomized Controlled Trial Bertrand Lukacs a,*, Joyce Loeffler b, Franck Bruye`re c, Pascal Blanchet d, Albert Gelet e, Patrick Coloby f, Alexandre De la Taille g, Philippe Lemaire h, Jean-Christophe Baron i, Jean-Nicolas Cornu a, Mounir Aout j, Helene Rousseau j, Eric Vicaut j for the REVAPRO study group a
Department of Urology, Tenon Hospital, Assistance publique Hoˆpitaux de Paris; University Paris VI, Paris, France; b Department of Urology, Pasteur Hospital, Nice University, Nice, France; c Department of Urology, University Hospital of Tours, Tours, France; d Department of Urology, Pointe-a`-Pitre University Hospital, Guadeloupe, West French Indies; e Department of Urology, Edouard Herriot Hospital, Lyon, France; f Department of Urology, Rene´ Dubos Hospital, Pontoise, France; g Department of Urology, Henri Mondor Hospital, Assistance publique Hoˆpitaux de Paris; University Paris XII, Cre´teil, France; h Department of Urology, Les Bleuets Clinic, Reims, France; i Department of Urology, Alliance Clinic, Saint Cyr sur Loire, France; j Clinical Research Unit, Lariboisie`re-Fernand
Widal Hospital, Assistance publique Hoˆpitaux de Paris; University Paris Diderot, Paris, France
Article info
Abstract
Article history: Accepted January 31, 2012 Published online ahead of print on February 7, 2012
Background: Evidence supporting the widespread use of GreenLight High Performance System (HPS) 120-W photoselective vaporization of the prostate (PVP) is lacking. Objective: To assess the noninferiority of PVP compared with transurethral resection of the prostate (TURP) on urinary symptoms and the superiority of PVP over TURP on length of hospital stay. Design, setting, and participants: A multicenter randomized controlled trial was conducted. Intervention: Patients underwent monopolar TURP or PVP with the GreenLight HPS 120-W laser. Measurements: International Prostate Symptom Score (IPSS), Euro-QOL questionnaire, uroflowmetry, Danish Prostate Symptom Score Sexual Function Questionnaire, sexual satisfaction, and adverse events were collected at 1, 3, 6, and 12 mo. The two groups were compared using the 95% confidence interval (CI) of median difference for testing noninferiority of the IPSS at 12 mo and the student t test for testing the difference in length of hospital stay. Results and limitations: A total of 139 patients (70 vs 69 men in each group) were randomized. Median IPSS scores at 12-mo follow-up were 5 (interquartile range [IQR]: 3–8) for TURP versus 6 (IQR: 3–9) for PVP, and the 95% CI of the difference of the median was equal to 2 to 3. Because the upper limit of the 95% CI was >2 (the noninferiority margin), the hypothesis of noninferiority could not be considered demonstrated. Median length of stay was significantly shorter in the PVP group than in the TURP group, with a median of 1 (IQR: 1–2) versus 2.5 (IQR: 2–3.5), respectively ( p < 0.0001). Uroflowmetry parameters and complications were comparable in both groups. Sexual outcomes were slightly better in the PVP group without reaching statistical significance.
Keywords: Transurethral resection of the prostate Photovaporization of the prostate Laser Randomized controlled trial
* Corresponding author. Urology Department, Tenon Hospital, 4 rue de la Chine, 75970 Paris Cedex 20, France. Tel. +01 56 01 64 95; Fax: +01 56 01 73 06. E-mail address: [email protected] (B. Lukacs). 0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2012.01.052
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Conclusions: The present study failed to demonstrate the noninferiority of 120-W GreenLight PVP versus TURP on prostate symptoms at 1 yr but showed that PVP was associated with a shorter length of stay in the hospital. Trial registration: NCT01043588. # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
1.
Introduction
(1 mo for 5-ARIs). All patients with a prostate-specific antigen (PSA) >4 who were candidates for prostate cancer screening underwent prostatic
Benign prostatic hyperplasia (BPH) is a highly prevalent disease, and its management represents an important economic burden in Western countries [1]. BPH is the major etiology of lower urinary tract symptoms (LUTS) in men >50 yr of age. These symptoms are usually assessed by the International Prostate Symptom Score (IPSS) and associated with a variable degree of bother. In cases of moderate to severely bothersome symptoms, medical treatment is appropriate. Surgical therapy, aiming at relieving obstruction, is indicated after the failure of maximal drug therapy or with complications of the disease [2]. Transurethral resection of the prostate (TURP) remains the reference standard, with which any new surgical innovation should be compared [3]. Photoselective vaporization of the prostate (PVP) by GreenLight laser has been presented as a minimally invasive surgical alternative to TURP, with several advantages such as reduced bleeding complications and short hospital stay [4–6]. However, PVP cannot be yet recommended as a first-line therapy because comparative studies against TURP, especially with the High Performance System (HPS) 120-W power device, are still lacking [3]. Only two monocentric randomized controlled trials (RCTs) focused on urinary parameters have been published with the GreenLight HPS 120-W laser [4,7]. Several issues remain unclear concerning PVP such as postoperative irritative symptoms [8], sexual outcomes, and the absence of pathologic material after the procedure resulting in the missed diagnosis of prostate cancer. Our primary goal was to compare the efficacy of PVP with GreenLight and TURP through a noninferiority hypothesis. The secondary aims were to compare adverse events, sexual outcomes, and quality of life after the two procedures.
2.
Patients and methods
2.1.
Study overview
This multicenter RCT was conducted in nine tertiary reference centers from 2009 to 2011. This study was conducted in accordance with the Good Clinical Practice Guidelines and the Declaration of Helsinki. The protocol was approved by our local institutional review board. All participants gave written informed consent before enrollment. This study was funded by a national grant for medical research (assessment of emerging medical therapies program, [STIC2007], French Ministry of Health).
2.2.
Participants
Patients >50 yr of age presenting LUTS/BPH requiring surgical management were screened to participate. Table 1 details the inclusion and exclusion criteria. If present, a treatment by a1-blockers, phytotherapy, or 5a-reductase inhibitors (5-ARIs) had to be stopped 1 wk before surgery
biopsies that were negative in all cases.
2.3.
Study design and data collection
At baseline and during the four follow-up visits, the usual urinary parameters were assessed: IPSS; bother score (question 8 of the IPSS questionnaire); maximum flow rate (Qmax); postvoid residual (PVR) volume; sexual parameters (Danish Prostate Symptom Score Sexual Function Questionnaire [DAN-PSSsex] and a global sexual satisfaction score between 0 and 6, similar to IPSS question 8; and quality-of-life scores (Euro-QOL questionnaire) (Table 2). A dedicated nonvalidated questionnaire was used to assess symptoms after 1 mo (Fig. 1).
2.4.
Interventions
Patients underwent monopolar TURP or PVP (GreenLight HPS 120-W laser; AMS, Minnetonka, MN, USA). All patients received antibiotic prophylaxis. Each local investigator was the only surgeon who did the procedures. All surgeons had to be well experienced in TURP and PVP before the study began. Perioperative data collected were duration of the procedure, irrigation type and volume, type and size of urinary catheter used, and length of hospital stay. During PVP, the total energy used, number of fibers, and the eventual use of electrical coagulation or resection were also assessed. All patients were discharged without catheter after a PVR control following catheter removal.
Table 1 – Inclusion and exclusion criteria of the REVAPRO study Inclusion criteria - IPSS 12 and bother score 3 (according to IPSS question 8) - Qmax <12 ml/s (associated with a >125-ml void) - Prostate volume between 25 ml and 80 ml - Postvoid residual volume <300 ml - Normal digital rectal examination - PSA <4 ng/ml or negative prostate biopsy if PSA between 4 and 10 ng/ml for patients <75 yr of age or with life expectancy >10 yr Exclusion criteria - Patients with urinary catheter before intervention - Active urinary tract infection - Impaired renal function - Unstable cardiac or pulmonary disease - Bladder disease or neurologic disease affecting bladder function - Altered urinary sphincter function, urethral stricture, bladder neck stenosis, active hematuria, or bladder stones - History of prostate or urethral surgery - Anorectal disease - Anticoagulation therapy that cannot be stopped or replaced without risk for the patient - Antiaggregant therapy that cannot be stopped without risk for the patient - Severe coagulopathy - ASA score >3 - Patient unable to complete questionnaires or having no medical insurance IPSS = International Prostate Symptom Score; Qmax = maximum flow rate; PSA = prostate-specific antigen; ASA = American Society of Anesthesiologists.
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Table 2 – Data collection schedule Visit no. Visit purpose Timing Written informed consent Inclusion/exclusion criteria Complete medical history and ASA score Digital rectal examination IPSS score IPSS bother score (question 8) DAN-PSSsex score Global sexuality score EURO-QOL score Maximum flow rate Postvoid residual volume Ultrasound prostate examination PSA blood testing Adverse events ‘‘One-month questionnaire’’ Perioperative parameters
V3
V4
V5
V6
V7
Inclusion visit
V1
Immediate postoperative visit
Follow-up visit
Follow-up visit
Follow-up visit
Follow-up visit
D 30
Day of discharge
M1 5 d
M3 15 d
M6 15 d
M12 30 d
U U U U U U U U U U U
U U U U U U U U
U U U U U U U U U U U
U U U U U U U U U U U U U
V2
Day of intervention (PVP or TURP) U U
U U
U
U U
U
U
ASA = American Society of Anesthesiologists; IPSS = International Prostate Symptom Score; DAN-PSSsex = Danish Prostate Symptom Score Sexual Function Questionnaire; PVP = photoselective vaporization of the prostate; TURP = transurethral resection of the prostate; PSA = prostate-specific antigen.
2.5.
Outcomes
results on urinary symptoms, with a shorter length of stay for PVP. Hence the main objective of the study was to assess the noninferiority of the IPSS
The primary outcome criteria were the IPSS score at 1 yr and the length of
score at 12 mo combined with the superiority of PVP over TURP on the
hospital stay. Our hypothesis was that PVP and TURP generate similar
hospital stay duration (shorter length of stay for PVP). Secondary outcomes
[(Fig._1)TD$IG]
were other urinary parameters (Qmax, PVR), PSA value, complications, sexual symptoms (DAN-PSSsex), sexual satisfaction, and quality of life (Euro-QOL questionnaire).
2.6.
Sample size
It was determined that taking into account a dropout rate of 15%, we needed to enroll 104 patients in each treatment arm to have a power (1) >90% for demonstrating the noninferiority of PVP versus TURP considering a noninferiority margin equal to 2 points of IPSS, assuming a standard deviation (SD) of 3 points for IPSS distribution in both groups (2) equal to 90% to detect a difference in length of stay of 1 d between the two techniques assuming an SD of 2 d.
2.7.
Randomization
Patients were randomized 1:1 in each group by blocks of four via a centralized computerized system to ensure a good balance of participant characteristics in each group. Randomization was stratified by centers. The randomization group for each patient was given by phone via a call center at the inclusion visit. Patients were not blinded to the surgical treatment.
2.8.
Statistical analysis
The statistical analysis was performed according to the intention-to-treat (ITT) principle. For patients lost to follow-up, data were analyzed with the last observation carried forward method. Results were summarized as the mean plus or minus SD for gaussian variables and the median and interquartile range (IQR) for nongaussian variables. Categorical variables were analyzed with the chi-square test or Fisher exact test as appropriate. Primary quantitative outcome variables were compared with the student t test or the Mann-Whitney U test as appropriate. The noninferiority hypothesis was considered demonstrated if the upper value of the 95% Fig. 1 – One-month questionnaire for urinary tract symptoms after endoscopic surgery of the prostate.
confidence interval (CI) limit of the difference of IPSS at 12 mo in PVP versus TURP was < 2 points. Because the statistical distribution of IPSS
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Table 3 – Baseline characteristics of the 139 patients included in the intention-to-treat evaluation Characteristics
TURP (n = 70)
PVP (n = 69)
Age, yr* 67.6 7.6 (51.2–88.7) Qmax* 7.76 2.64 (2.3–14.7) y PVR 75 (28–126) PSA 2.72 (1.7–4.45) Prostate volume* 50.11 14.73 (20–85) Prostate size <49 ml§ (%) 28 (40) 27 (40.3) Presence of a median lobe§ (%) Preoperative IPSSy 20 (15–23) 8.5 (6.5–11) Preoperative IPSS storage subscore (questions 2, 4, 7)y Preoperative IPSS 10.5 (8–14) storage subscore (questions 1, 3, 5, 6)y Sexual satisfaction scale§ (%) 0 Very satisfied 5 (10.2) 1 Satisfied 14 (28.6) 2 Rather satisfied 7 (14.3) 3 Not satisfied, not 11 (22.4) unsatisfied 4 Rather unsatisfied 5 (10.2) 5 Unsatisfied 3 (6.1) 6 Very unsatisfied 4 (8.2) 6 (0–15) DAN-PSSsex scorey 75 [65–85] Euro QOL global scorey
66.9 7.8 (51.7–88.3) 7.79 2.75 (2–15) 89.5 (30–158.5) 2.41 (1.4–4.2) 50.54 16.53 (20–80) 39 (56.5) 24 (34.8) 22 (17–26) 9 (7–12)
13 (9–16)
9 (15.5) 9 (15.5) 8 (13.8) 11 (19) 5 (8.6) 6 (10.3) 10 (17.2) 6.5 (2–18) 70 [60–80]
TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate; Qmax = maximum flow rate; PVR = postvoid residual; ITT = intention to treat; PSA = prostate-specific antigen; IPSS = International Prostate Symptom Score; DAN-PSSsex = Danish Prostate Symptom Score Sexual Function Questionnaire. * Results are given as mean plus or minus standard deviation (range). § Results are given in number of subjects (percentage). y Results are given as median (interquartile range).
was not gaussian, the difference in median and bootstrap CI was used. As recommended for a noninferiority test, an analysis in per protocol populations (ie, patients without major violations) was also conducted. For the main hypothesis, results were considered significant if both hypotheses (noninferiority of PVP vs TURP regarding IPSS at 1 yr and hospital stay significantly shorter in the PVP group) were satisfied. The p values <0.05 were regarded as significant.
3.
Results
3.1.
Population
because they did not come to the hospital for the operation and one because of a contraindication to anesthesia). For all outcomes, the ITT analysis was then conducted on 136 patients who had at least one complete follow-up evaluation (68 men in both groups). IPSS at 12-mo follow-up was available in 125 patients. Figure 2 presents the flowchart. 3.2.
IPSS values at 12 mo-follow-up were not significantly different between the two groups (5 [3–8] for TURP vs 6 [3–9] for PVP; p = 0.494). The 95% CI of the difference of median IPSS at 12 mo was 2 to 3 (the difference in median was 0 with a 95% CI [2 to 2.5] in the per protocol [PP] population). Because the upper limit of the 95% CI was >2 (the noninferiority margin), the hypothesis of noninferiority could not be considered as demonstrated. Median length of stay was significantly shorter in the PVP group than in the TURP group (1 [1,2] vs 2.5 [2–3.5], respectively; p < 0.0001). Figure 3 shows the evolution of IPSS and Qmax during followup. The results for IPSS variation were not significantly different when stratified in function of prostate volume categorized in function of median or quartiles values or smaller/larger than 70 g (interaction p values were 0.55, 0.59, and 0.38, respectively). The results for stratification by size are listed in Table 4. 3.3.
Secondary efficacy outcomes
Qmax, PVR, PSA, and quality of life evaluated at 1 yr were not significantly different in the two groups (Table 5). DANPSSsex score, DANPSSsex subscores, and global sexual satisfaction were not significantly different in the two groups at last follow-up (Table 6). Evolution between preoperative and postoperative erection, ejaculation, and global sexual satisfaction scores showed a trend for improvement of sexual symptoms in the PVP group (Table 6). When improved and unchanged patients were grouped and compared with worsened patients in both arms, evolution of erection and ejaculation were better in the PVP group ( p = 0.04 and p = 0.04, respectively). 3.4.
A total of 139 men were randomized and described in the baseline data (Table 3). Three patients were not treated (two
Primary outcome
Perioperative data
The median duration of the procedure was longer in the PVP group than in the TURP group (71 [55–95] vs 55 [45–65] min, respectively; p = 0.0001). At the end of the procedure, no
Table 4 – International Prostate Symptom Score variation results stratified by prostate size*
y
TURP PVPy Means difference (95% CI) p value
Prostate weight <49 g
Prostate weight 49 g
Prostate weight 70 g
5.38 (3.27–7.49) 6.34 (4.54–8.14) 0.958 (1.86 to 3.78) 0.4983
6.79 (4.91–8.66) 6.80 (4.49–9.11) 0.014 (2.96 to 2.99) 0.9924
7.94 (4.90–10.97) 6.26 (3.23–9.30) 1.68 (5.98 to 2.63) 0.4228
PVP = photoselective vaporization of the prostate; TURP = transurethral resection of the prostate; CI = confidence interval. Data are presented stratified in two groups according to the overall median value of prostate size (49 g) and for the group of prostates >70 g. y Adjusted mean (95% CI). *
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[(Fig._2)TD$IG]
Assessed for eligibility (n = 142)
Enrollment
Excluded (n = 3) ♦ Not meeting inclusion criteria (n = 3)
Randomized (n = 139)
Allocaon Allocated to TURP (n = 70) -3 received PVP (3 refused randomization result)
Allocated to PVP (n = 69) -3 received TURP (1 refused randomization result, 2 without explanations)
-2 received both TURP and PVP (investigator's error)
-1 received both PVP and TURP (failure of the laser device)
-2 without intervention (1 contraindication to anesthesia and 1 did not come to the hospital)
Follow -Up
-1 without intervention (did not come to the hospital)
Lost to follow-up (n = 5)
Lost to follow-up (n = 9)
- 1 refused to continue to participate in the study; 4 lost to follow-up
- 1 death, 3 refused to continue to participate in the study, 5 lost to follow-up
Analysis Analyzed (n = 70)
Analyzed (n = 69)
Fig. 2 – Study flowchart. Data concerning dropouts were analyzed with the last observation carried forward method. PVP = photoselective vaporization of the prostate; TURP = transurethral resection of the prostate.
difference was noted in the size of the catheter used (between 18F and 22F for all patients), but only 37 patients in the PVP group had a two-way irrigation catheter placed versus 66 patients in the TURP group ( p < 0.0001). Mean plus or minus SD power used during PVP was 256, 4 117.0 kJ (0.334–574), for a median duration of vaporization reaching 43 (38–60) min. In six PVP procedures, a monopolar resector was used for resection and coagulation because of failure of the PVP technique; in all cases, this occurred because of perioperative bleeding without capsule perforation. 3.5.
Complications
Overall, perioperative complication rates (39.7% for TURP vs 26.5% for PVP) were not different in the two groups, except for hematuria (Table 7). One patient had to be reoperated in the PVP group (none in the TURP group). Two patients in the PVP group and one patient in the TURP group were discharged with an indwelling urinary catheter. A questionnaire at 1 mofollow-up did not show any differences between the two groups (Table 8).
Late complication rates were comparable in both groups with 16 patients hospitalized (11 TURP and 5 PVP) because of acute urinary retention (5 TURP, 2 PVP), urinary infection (5 TURP, 1 PVP), or other reasons (1 TURP, 2 PVP). 4.
Discussion
More evidence is needed to support the diffusion of the PVP technique as a first-line alternative to TURP [3]. The present study, as the first multicenter RCT comparing PVP and TURP, offers strong evidence that PVP and TURP efficacy are comparable in relieving symptoms of LUTS/BPH. Like the two other RCTs available in the literature [4,7], IPSS scores were not statistically different between the two groups after 1-yr follow-up. But the absence of a significant difference should not be considered a demonstration of the noninferiority of PVP versus TURP. It is the reason why, in contrast with the two other RCTs, the present study used a noninferiority approach for the IPSS score at 12 mo (combined with a superiority approach regarding hospital length of stay).
[(Fig._3)TD$IG]
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Table 5 – Nonsexual secondary outcomes evaluated during follow-up Data
TURP (n = 68)
PVP (n = 68)
p value
Urinary parameters* Qmax 1 mo 14.9 (11.2–18.1) 16 (10.6–21.9) 0.35 3 mo 15.7 (12–19) 17 (12–23) 0.30 6 mo 17.1 (10.9–21) 16.3 (13.5–20.8) 0.68 12 mo 16.8 (12.1–24.9) 16.7 (12–22.7) 0.71 PVR 1 mo 13 (0–50) 20 (0–45) 0.52 3 mo 15 (0–34) 10 (0–34) 0.66 6 mo 19 (0–38) 10 (0–39.5) 0.46 12 mo 7 (0–32) 0 (0–43) 0.75 1.51 (0.61–2.44) 1.81 (0.87–3.60) 0.10 PSA, ng/ml,* at 1 yr 24.7 (18.5–35) 30 (22–40) 0.09 Prostate volume,* ml, at 1 yr Overall satisfactiony (according to a four-level questionnaire) at 1-yr follow-up (%) Very satisfied 23 (37.1) 28 (44.4) Satisfied 31 (50) 25 (39.7) 0.75 Unsatisfied 7 (11.3) 9 (14.3) Very unsatisfied 1 (1.6) 1 (1.6) 75 (60–85) 77 (69.5–87.5) 0.56 EuroQol global score* TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate; Qmax = maximum flow rate; PVR = postvoid residual; PSA = prostate-specific antigen. * Data are given as median (interquartile range). y Data are given as number (percentage).
Fig. 3 – Box plot graphs showing evolution of the urinary parameters during follow-up (data are given as median and interquartile range). (A) Evolution of International Prostate Symptom Score (IPSS); (B) evolution of maximum flow rate (Qmax) in milliliters per second; (C) evolution of postvoiding residual (PVR) in milliliters. PVP = photoselective vaporization of the prostate; TURP = transurethral resection of the prostate.
This noninferiority approach is the only method that allows the conclusion that the difference between the two methods is not too large to permit the substitution of the old technique (TURP) by the new one (PVP). When considering the results of the present study regarding the noninferiority of IPSS, several aspects should be considered. First, we have chosen a very stringent noninferiority margin (ie, only 2 points of IPSS). Both the recruitment (lower than expected) and the SD of IPSS (larger than expected) increased the width of the 95% CI of IPSS. For these reasons, the upper limit of the 95% CI of the difference in medians (ie, 3 for the ITT population and 2.5 for the PP population) exceeded the 2 points corresponding to the noninferiority margin and thus did not allow us to formally conclude noninferiority, even if the observed differences in median IPSS were very small (ie, equal to 1 in the ITT population and to 0 in the PP population). However, these 95% CI values show that if it exists, the difference between the two methods is not clinically meaningful because their upper limits were lower than 3.1, that is, the limit of patient-perceptible IPSS variation in a clinical setting [7,9]. Qmax and PVR were also comparable in the two groups. Since length of stay was inferior in the PVP group because of a reduced need for postoperative irrigation and catheterization, PVP appears to be a useful alternative to TURP with potential benefits in clinical practice. These results, related to the reduced rate of bleeding complications already reported by others with PVP [10,11] can be explained by the tissular effects of GreenLight laser that lead to an optimal coagulation depth of 3 mm in prostatic tissue [12]. However, several issues have been raised about the potential drawbacks of the PVP technique,
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Table 6 – (a) Results from the Danish Prostate Symptom Score Sexual Function Questionnaire and sexual satisfaction questionnaire at 1-yr follow-up*; (b) evolution of sexual satisfaction*, erection score, and ejaculation score at last follow-up compared with baseline a. Sexual symptoms
TURP group (n = 65)
No. of patients sexually active at 12 mo (%) Total DANPSSsex score Total subscore A (symptoms) Total subscore B (bother) Question 1 Presence of erections (1A) Yes, with a normal rigidity Yes, with a slight reduction in rigidity Yes, with a big reduction in rigidity No, I cannot get an erection Related bother (1B) Not at all A little bit Moderate Very much Question 2 Presence of ejaculations (2A) Yes, with a normal amount of semen Yes, with a slightly reduced amount of semen Yes, with a very reduced amount of semen No ejaculation Related bother (2B) Not at all A little bit Moderate Very much Question 3 Pain/discomfort while ejaculating (3A) No Yes, slight pain/discomfort Yes, moderate pain/discomfort Yes, severe pain/discomfort Related bother (3B) Not at all A little bit Moderate Very much Overall sexual satisfaction score
50 6 3 3
(82) (2–15) (2–4) (1–5)
PVP group (n = 60) 43 5 2 2
(76.8) (1–15) (1–4) (1–5)
p value
0.68 0.56 0.28
17 19 11 3 14 17 8 11 – –
21 13 7 2 13 17 4 9 – –
0.55 0.79
6 14 13 17 18 14 11 7 – –
11 9 10 13 13 13 9 8 – –
0.40 0.90
46 4 0 0 28 12 3 7 – – 2 (1–4)
37 4 2 0 31 6 3 3 – – 2 (1–4)
0.41 0.37
0.42
Total (n = 87)
p value
b. TURP (n = 44)
PVP (n = 43)
Evolution of sexual satisfaction after surgery compared with baseline (%) Improved 15 (34.1) Unchanged 15 (34.1) Worsened 14 (31.8)
TURP (n = 39)
19 (44.2) 18 (41.9) 6 (14)
PVP (n = 39)
Evolution of erection score after surgery compared with baseline Improved 9 (23.1) Unchanged 19 (48.7) Worsened 11 (28.2) Evolution of ejaculation score after surgery compared with baseline Improved 4 (10.3) Unchanged 11 (28.2) Worsened 24 (61.5)
34 (39) 33 (38) 20 (39)
Total (n = 78)
0.14
p value
8 (20.5) 27 (69.2) 4 (10.3)
17 (22) 46 (59) 15 (19)
0.09
5 (12.8) 19 (48.7) 15 (38.5)
9 (12) 30 (38) 39 (50)
0.10
TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate. * Data about sexual satisfaction come from 87 sexually active patients. Data about erection and ejaculation come from 78 patients with valid DAN-PSSsex data before and after the procedure (39 patients in each group). Data are given as numbers (percentages).
especially in regard to transient dysuria and irritative symptoms in the first months after surgery, adverse sexual events [13–16], and the absence of pathologic material with PVP.
In the current study we specifically focused on storage symptoms during the early postoperative period that could have an impact on the short-term clinical benefit of the procedure by generating urinary bother. Because IPSS is not
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Table 7 – Early postoperative side effects* TURP (n = 68) Early postoperative side adverse events Postoperative transfusion 1 (1.5) Infection 3 (4.4) Pain/Bother 7 (10.3) Other complications 5 (7.4) Macroscopic hematuria 21 (30.9) Overall 27 (39.7)
PVP (n = 68)
1 2 7 7 7 18
p value
(1.5) (2.9) (10.3) (10.3) (10.3) (26.5)
1.00 1.00 1.00 0.55 0.003 0.10
TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate. * Data are given as numbers (percentages).
Table 8 – One-month postoperative questionnaire results TURP group (n = 62) Question 1: Pain (%) No 16 (25.8) Mild 19 (30.6) Moderate 23 (37.1) Intense 4 (6.5) Question 2: Hematuria (%) No 11 (17.7) Pink color 34 (54.8) Red blood in urine 10 (16.1) Clots 7 (11.3) Question 3: Urgency (%) No 17 (27.4) Yes, acceptable 21 (33.9) Yes, bothersome 20 (32.3) Yes, intolerable 4 (6.5) Question 4: Incontinence (%) No 39 (62.9) Yes, a few times 15 (24.2) Yes, bothering 4 (6.5) Yes, and I had to wear pads 4 (6.5) Question 5: Stream improvement (%) Improved 54 (87.1) Unchanged 5 (8.1) Diminished 3 (4.8) Dripping 0 (0)
PVP group (n = 67)
p value
16 22 25 4
(23.9) (32.8) (37.3) (6)
0.99
15 30 14 8
(22.4) (44.8) (20.9) (11.9)
0.70
17 24 21 5
(25.4) (35.8) (31.3) (7.5)
0.99
33 19 5 10
(49.3) (28.4) (7.5) (14.9)
0.34
55 5 4 2
(83.3) (7.6) (6.1) (3)
0.79
satisfaction question (similar to IPSS question 8 evaluating the global urinary condition). Our results show that erectile and ejaculatory disorders were not different in the two groups at 1-yr follow-up. However, there was a trend for an improvement of erection, ejaculation, and sexual satisfaction in the PVP arm when 12-mo values were compared with baseline. These results, already suggested for ejaculation [6], still need further investigation. Some authors have stated that a potential drawback of PVP could be the absence of tissue for pathologic material analysis [20]. In the present study, more than simply assessing the number of patients diagnosed with cancerous tissue after TURP, we evaluated the number of patients who underwent a curative treatment of prostate cancer after TURP. This was the case for 2 of 68 patients 1 yr after diagnosis. Only one of them had a normal digital rectal examination and a PSA <4 ng/ml before surgery. Although this study as a prospective RCT meets the highest standards of criteria for evidence, the limited followup (1 yr) does not permit us to draw mid- or long-term conclusions. 5.
TURP = transurethral resection of the prostate; PVP = photoselective vaporization of the prostate.
Conclusions
Although the noninferiority between the two techniques could not be formally demonstrated regarding the preestablished criteria of the present study, PVP seems an acceptable alternative to TURP with close results on LUTS improvement in the short term. PVP is associated with a reduced hospital stay with less postoperative irrigation and hematuria. Postoperative symptoms and complications were similar in both arms. Longer follow-up studies are required to confirm the clinical benefits of this technique for the surgical management of LUTS/BPH. Author contributions: Bertrand Lukacs had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Lukacs, Vicaut, Aout. Acquisition of data: Lukacs, Loeffler, Bruye`re, Blanchet, Gelet, Coloby, De la Taille, Lemaire, Baron Analysis and interpretation of data: Rousseau, Aout, Lukacs, Vicaut, Cornu. Drafting of the manuscript: Cornu, Lukacs.
designed for this purpose and poorly targets the specific symptoms of pain while voiding or urgency, we used a dedicated questionnaire. We found no difference between the two groups (Table 8). Although the subscore of storage symptoms was similar in the two groups at inclusion (Table 3), because this questionnaire was completed at 1 mo and was not diary information, recall bias could influence the results for short-term transient postoperative symptoms. Sexual function after PVP has not been adequately evaluated [14,17], and some have questioned whether this procedure has an impact on erectile function [13]. Here we decided to explore sexuality as a multidimensional variable through the validated DANPSSsex score, assessing both erectile and ejaculatory symptoms as well as bother. Given that the urinary symptoms themselves have been linked to sexual function as a whole [18,19], we added a global sexual
Critical revision of the manuscript for important intellectual content: Loeffler, Bruye`re, Coloby, De la Taille. Statistical analysis: Aout, Vicaut. Obtaining funding: Lukacs, Vicaut. Administrative, technical, or material support: Aout. Supervision: Lukacs. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Franck Bruye`re is a proctor and consultant for AMS. Funding/Support and role of the sponsor: French Ministry of Health supported this study by funding the entire study after approval of the initial protocol (GRANT #STIC2007).
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