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Keywords:

  • prostate;
  • holmium;
  • prostatectomy;
  • benign prostatic enlargement

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Study Type – Therapy (RCT)

Level of Evidence 1b

What's known on the subject? and What does the study add?

HoLEP has been widely adopted worldwide as an alternative to TURP but long term results have been lacking despite the strong scientific basis for the technique.

This study provides long-term results from the original RCT comparing the two techniques.

OBJECTIVE

  • • 
    To assess the durability of holmium laser enucleation of prostate in comparison to transurethral resection of the prostate (TURP).

PATIENTS AND METHODS

  • • 
    Patients were enrolled in the present study between June 1997 and December 2000 and followed per protocol.
  • • 
    All patients were urodynamically obstructed with a prostate volume of between 40 and 200 mL.
  • • 
    At long-term follow-up, variables assessed included Benign Prostatic Hyperplasia Impact Index (BPHII), International Continence Society Short Form Male questionnaire (ICSmale-SF) and the International Index of Erectile Function (IIEF).
  • • 
    Adverse events, including the need for retreatment, were specifically assessed.

RESULTS

  • • 
    Thirty-one (14 holmium laser enucleation of the prostate [HoLEP] and 17 TURP) of the initial 61 patients were available, with 12 deceased and 18 lost to follow-up.
  • • 
    The mean (range) follow-up was 7.6 (5.9–10.0) years and the mean (±sd) age at follow-up was 79.8 (±6.2) years.
  • • 
    The mean (±sd) values (HoLEP vs TURP) were as follows: maximum urinary flow rate (Qmax), 22.09 ± 15.47 vs 17.83 ± 8.61 mL/s; American Urological Association (AUA) symptom score, 8.0 ± 5.2 vs 10.3 ± 7.42; quality of life (QOL) score 1.47 ± 1.31 vs 1.31 ± 0.85; BPHII, 1.53 ± 2.9 vs 0.58 ± 0.79; IIEF-EF (erectile function), 11.6 ± 7.46 vs 9.21 ± 7.17; ICSmale Voiding Score (VS), 4.2 ± 3.76 vs 3.0 ± 2.41; ICSmale Incontinence Score (IS), 3.07 ± 3.3 vs 1.17 ± 1.4.
  • • 
    There were no significant differences in any variable between the two groups beyond the first year.
  • • 
    Of the assessable patients, none required re-operation for recurrent BPH in the HoLEP arm and three (of 17) required re-operation in the TURP arm .

CONCLUSION

  • • 
    The results of this randomized trial confirm that HoLEP is at least equivalent to TURP in the long term with fewer re-operations being necessary.

Abbreviations
BPHII

BPH Impact Index

HoLEP

holmium laser enucleation of the prostate

OP

open prostatectomy

PVR

post-void residual volume.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Durability is one of the most important aspects differentiating traditional treatments such as open prostatectomy (OP) and TURP from many of the newer modalities. Re-operation rates after TURP vary, but are often quoted at 1%/year after surgery [1].

A large series quoted a re-operation rate at 8 years of 7.4% [2]. OP is generally better again with long-term re-operation rates of ≈2–5% [1]. As data mature with holmium laser enucleation of the prostate (HoLEP), its durability relative to these established alternatives is becoming apparent. A recent report described the re-operation rate for HoLEP at 6 years as 1.4% [3].

Many minimally invasive procedures, including other laser techniques, for treating bladder outflow obstruction due to benign prostatic enlargement have come and gone over the last 15 years. One of the main issues exposed with years of use of some of these techniques is the failure of the treatment over time and the need for re-treatment [1]. Other issues leading to the demise of these procedures include significant patient dissatisfaction with the early results (irritative symptoms or prolonged catheterization), inefficiency and unacceptability to the surgeon of the primary treatment, reimbursement issues and lack of ongoing device company support and marketing. Commercial issues notwithstanding, durability concerns often become the most important determinant of the ultimate survival of a given technique for the practising urologist.

Holmium prostatectomy has been around in various forms since 1994 [4]. In the quest for increasing efficiency and in the pursuit of improved outcomes, the procedure has evolved from a combination procedure (with neodymium-doped yttrium aluminium garnet [Nd:YAG]), to an ablative procedure, to excisional techniques involving resection of small fragments and, most recently, anatomical enucleation of whole lobes [5]. HoLEP with tissue morcellation was first performed in our institution (Tauranga Hospital) in 1996 and has since been adopted in many centres throughout the world [6].

The preliminary data from this randomized trial comparing HoLEP and TURP were originally reported in 2003 [7] with subsequent publication of 2-year data in 2006 [8]. The long-term data and further analysis of these patients are now presented.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Patients in this randomized trial were originally enrolled between June 1997 and December 2000 and followed per protocol. All patients were investigated initially with medical history and physical examination, DRE, PSA level, urine analysis, AUA symptom score, quality of life (QoL) score, transrectal ultrasonography (TRUS) prostate volume measurement, post-void residual volume (PVR) measurement, maximum urinary flow rate (Qmax) and pressure-flow urodynamic assessment. Inclusion criteria included a TRUS volume of 40–200 mL, Qmax≤ 15 mL/s or less, AUA symptom score ≥ 8, PVR < 400 mL, and Schafer grade ≥ 2. Those patients who had undergone previous prostatic or urethral surgery, who had had carcinoma of the prostate or who were in urinary retention were excluded from the study. Initial follow-up was at 1, 3, 6, 12 and 24 months after surgery.

For the current analysis, these patients were contacted initially from the study database information, the national hospital database or the telephone book as a last resort. All available patients were subsequently interviewed by an independent research nurse (C.J.K.) and had their case notes reviewed. Variables collected at follow-up included Qmax, AUA score, QoL score, BPH Impact Index (BPHII), International Continence Society Short Form Male questionnaire (ICSmale-SF) and the International Index of Erectile Function (IIEF). Adverse events including continence and re-operation were specifically addressed. The case notes of all patients were scrutinized, including those of patients who were deceased or lost to follow-up. Family practitioners were also contacted in these latter cases to ascertain any information regarding adverse events or the need for further treatment. No blood or urine tests were collected.

The data did not meet normality assumptions and therefore the analyses comparing the two groups were performed using the Mann–Whitney U-test.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

There were 61 patients originally recruited for the present study: 31 in the HoLEP arm and 30 in the TURP arm. This was based on a power calculation using α= 0.05 and β= 0.20 based on a previous randomized trial of holmium resection vs TURP designed to show a 10% difference in hospital stay and catheterization time. From the original study cohort, 31 (14 HoLEP, 17 TURP) of the initial 61 patients were available, with 12 deceased and 18 lost to follow-up. Three of these 18 patients were known to have left the country and no other information was obtainable about the remaining 15 lost to follow-up. The patient demographics at baseline are given in Table 1. There was no significant difference in preoperative variables between the two groups.

Table 1.  Baseline demographic data
 HoLEPTURP
Age71.70 ± 1.1070.30 ± 1.00
AUA score26.39 ± 6.1423.72 ± 6.44
Qmax, mL/s8.28 ± 2.188.26 ± 2.18
PVR, mL116.14 ± 85.09126.67 ± 116.77
QoL score4.79 ± 1.074.70 ± 1.10
TRUS volume, mL77.68 ± 32.1370.00 ± 27.78

Perioperative data are given in Table 2. While resectoscope time was significantly shorter for TURP, HoLEP was equally efficient when this time was adjusted for tissue retrieved. There were significant advantages of HoLEP with respect to the amount of tissue removed, catheter time and hospital stay: 6.7% of patients in the HoLEP group required bladder irrigation after surgery, compared with 70% in the TURP group.

Table 2.  Perioperative comparative data
 HoLEPP valueTURP
Resectoscope time, min62.1 ± 5.9<0.00133.1 ± 3.7
Pathological weight, g40.4 ± 5.7<0.05024.7 ± 3.4
Catheter time, h17.7 ± 0.7<0.01044.9 ± 10.1
Hospital time, h27.6 ± 2.7<0.00149.9 ± 5.6

Postoperative outcomes are given in Table 3. There was no statistically significant difference in outcomes up to 7 years of follow-up. Urodynamic data have been published previously [7]. At 6 months after surgery, the change in detrusor pressure at maximum flow (PdetQmax), Schafer grade and TRUS volume in both groups were significantly lower than at baseline. The reduction in PdetQmax was significantly greater in the HoLEP group.

Table 3.  Patient outcome scores over time
Follow-upAUA scoreQoLQmax, mL/s
1 Month   
 HoLEP8.6 ± 1.22.7 ± 0.422.3 ± 2.3
 TURP5.7 ± 1.11.6 ± 0.318.4 ± 1.6
3 Months   
 HoLEP4.8 ± 0.81.8 ± 0.424.2 ± 1.7
 TURP2.4 ± 0.91.9 ± 0.618.9 ± 1.9
6 Months   
 HoLEP6.0 ± 1.01.6 ± 0.321.3 ± 2.1
 TURP4.8 ± 0.71.5 ± 0.218.9 ± 2.8
12 Months   
 HoLEP4.6 ± 0.71.5 ± 0.521.3 ± 2.1
 TURP4.7 ± 0.91.4 ± 0.318.9 ± 2.8
24 Months   
 HoLEP6.1 ± 1.01.25 ± 0.221.0 ± 2.0
 TURP5.2 ± 0.81.25 ± 0.219.3 ± 2.2
92 Months   
 HoLEP8.0 ± 5.201.47 ± 1.3022.09 ± 15.47
 TURP10.3 ± 7.421.31 ± 0.8517.83 ± 8.61

There was no difference between the two groups when analysing the BPHII (Table 4). Similarly, when analysing ICSmale SF data, there was no difference in analysis of voiding symptoms, incontinence, pad usage, frequency, nocturia and QoL.

Table 4.  BPH Impact Index and ICSmale-SF
 HoLEPTURP
BPHII1.53 ± 2.90.58 ± 0.79
ICSmale VS4.2 ± 3.763.00 ± 2.41
ICSmale IS3.07 ± 3.391.17 ± 1.4
ICSFreq0.93 ± 0.700.75 ± 0.62
ICSNoct1.73 ± 0.881.83 ± 1.19
ICSQoL0.73 ± 0.880.33 ± 0.49

The IIEF-15 data are given in Table 5. There was no significant difference between the two groups. Preoperative and postoperative PSA data for the present study were incomplete and have been excluded from the analysis.

Table 5.  International Index of Erectile Function
 HoLEPTURP
Erectile function11.6 ± 7.469.21 ± 7.17
Orgasmic function2.73 ± 3.172.79 ± 4.04
Sexual desire5.00 ± 2.625.00 ± 2.60
Intercourse2.33 ± 3.582.21 ± 3.38
Overall satisfaction5.00 ± 2.224.61 ± 2.70

Of the assessable patients, none required re-operation for recurrent BPH in the HoLEP arm and three (of 17) required re-operation in the TURP arm. All three patients in the TURP group requiring re-operation had HoLEP performed for prostatic adenoma regrowth after TURP.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

There have been many proposed alternative treatments to TURP for treating BPH; an ideal treatment is one that acutely removes significant amounts of prostatic adenoma and has minimal peri-operative morbidity while providing equivalent and durable patient outcomes. HoLEP is the only technique that has been proven to meet all these criteria and the present study confirms that the procedure provides long-standing patient benefit. This paper also shows the logistic issues involved in following up an elderly population; half of the study patients were lost to follow-up, but this is not unusual for the period of time that elapsed since the beginning of the study.

The peri-operative advantages of HoLEP have been established for some time; the initial publication from this study confirmed the procedure's superiority over TURP, with reduced peri-operative morbidity, improved efficiency, and reduced catheter time and hospital stay [7]. The outcomes were equivalent at 12 months follow-up. This has subsequently been confirmed in other well designed controlled trials comparing HoLEP with TURP or OP [9–11].

While several alternative surgical treatments for BPH have lower peri-operative morbidity than TURP, few offer the durable improvement that TURP does. A recent study of over 20 000 patients found a re-operation rate of 7.4% at 8 years follow-up [2]. The excellent durability of HoLEP has long been suspected. Earlier studies have shown that more prostate tissue is removed at HoLEP than at TURP in matched prostates [7,9]. Reductions in postoperative TRUS volume after HoLEP have also been superior, as has postoperative PSA reduction as a marker of adequacy of tissue removal. In addition, the present investigation has previously shown that HoLEP is urodynamically superior to TURP in treating bladder outflow obstruction, and this has been discussed as another indirect marker for durability [7].

The present study confirms that HoLEP is a durable procedure. There was no difference in subjective or objective outcomes between TURP and HoLEP at >7 years follow-up. There were no re-operations in the HoLEP group compared with three in the TURP group. This confirms our previously published results and is similar to other long-term data. Vavassori et al. [12] published 3-year follow-up data on 330 consecutive patients showing sustained improvement at that point. The re-operation rate for recurrent/residual adenoma was 2.7%. Ahyai et al. [10] published 3-year data comparing HoLEP and TURP in 200 patients. At 2 years, symptom scores were significantly lower in the HoLEP group, but at 3 years there was no difference in outcome measures or re-operation rates between the two groups [10]. Elzayat et al. [13] have also published long-term data which, at a mean follow-up of 48 months, show similar prolonged efficacy and low late complication rates. Interestingly, when analysing the re-operations in that series, four of the five situations in which patients required re-intervention occurred early in those surgeons' learning curve. In Kuntz's [14] pooled analysis of HoLEP, 1.8% of 1800 patients required re-operation after HoLEP. A recent study of 1000 cases from Krambeck et al. [15] further confirms this finding.

HoLEP's durability in very large or huge prostate glands has also been established. Kuntz et al. [16] described their 5-year data comparing OP to HoLEP for prostates > 100 g. At 5 years, both groups had similar outcomes, with mean IPSS scores of 3.0 and mean Qmax of 24.4 mL/s. Re-operation rates were low, 5% in the HoLEP group and 6.7% in the OP group. There was no difference in the incidence of delayed urethral stricture formation or bladder neck contracture [16].

By contrast, there are few quality studies examining the durability of other minimally invasive modalities with TURP. For example, most of the photoselective vaporisation of the prostate (PVP) ablation literature is of ‘level of evidence 4’, being uncontrolled, retrospective case series [17].

The main limitation of the present study is the lower numbers of patients at 7 years of follow-up than in the original study. This limited the power of the analysis that could be performed (including sub-group analysis), and is a function of the long-term follow-up and the age of the patients concerned. A much larger initial trial would have been required to maintain high numbers at this duration of follow-up. The power calculations for the original study as described in the Patients and Methods section validate the sample size.

Other recurring concerns are the supposed long learning curve and the claim of non-reproducibility of results published from centres associated with the development of the holmium laser. The learning curve has been repeatedly examined and has not proven to be as onerous as claimed [13]. The procedure is now widespread internationally and has been producing good results.

In conclusion, the results of this randomized trial confirm that HoLEP is at least equivalent to TURP in the long term, with fewer re-operations necessary.

CONFLICT OF INTEREST

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Peter J. Gilling is a meeting participant for Lumenis Inc.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES
  • 1
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  • 2
    Madersbacher S, Lackner J, Brossner C et al. Reoperation, myocardial infarction and mortality after transurethral and open prostatectomy: a nation-wide, long-term analysis of 23,123 cases. Eur Urol 2005; 47: 499504
  • 3
    Gilling PJ, Aho TF, Frampton CM et al. Holmium laser enucleation of the prostate: results at 6 years. Eur Urol 2008; 53: 7449
  • 4
    Gilling PJ, Cass CB, Malcolm AR et al. Combination holmium and Nd:YAG laser ablation of the prostate: initial clinical experience. J Endourol 1995; 9: 1513
  • 5
    Fraundorfer MR, Gilling PJ. Holmium:YAG laser enucleation of the prostate combined with mechanical morcellation: preliminary results. Eur Urol 1998; 33: 6972
  • 6
    Tan A, Liao C, Mo Z et al. Meta-analysis of holmium laser enucleation versus transurethral resection of the prostate for symptomatic prostatic obstruction. Br J Surg 2007; 94: 12018 (review)
  • 7
    Tan AHH, Gilling PJ, Kennett KM et al. Randomized trial comparing holmium laser enucleation of prostate with transurethral resection of prostate for treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200 grams). J Urol 2003; 170: 12704
  • 8
    Wilson LC, Gilling PJ, Williams A et al. A randomised trial comparing holmium laser enucleation versus transurethral resection in the treatment of prostates larger than 40grams: results at 2 years. Eur Urol 2006; 50: 56973
  • 9
    Montorsi F, Naspro R, Salonia A et al. Holmium laser enucleation versus transurethral resection of the prostate: results from a 2-centre, prospective, randomized trial in patients with obstructive benign prostatic hyperplasia. J Urol 2008; 179 (5 Suppl.): S8790
  • 10
    Ahyai S, Kuntz R, Lehrich K. Holmium laser enucleation versus transurethral resection of the prostate: 3-year follow-up results of a randomized clinical trial. Eur Urol 2007; 52: 145663
  • 11
    Kuntz R, Ahyai S, Lehrich K. Transurethral holmium laser enucleation of the prostate compared with transvesical open prostatectomy: 18-month follow-up of a randomized trial. J Endourol 2004; 18: 18991
  • 12
    Vavassori I, Valenti S, Naspro R et al. Three-year outcome following holmium laser enucleation of the prostate combined with mechanical morcellation in 330 consecutive patients. Eur Urol 2008; 53: 599604
  • 13
    Elzayat EA, Elhilali MM. Holmium laser enucleation of the prostate (HoLEP): long-term results, reoperation rate, and possible impact of the learning curve. Eur Urol 2007; 52: 146571
  • 14
    Kuntz RM. Current Role of Lasers in the Treatment of BPH. Eur Urol 2006; 49: 9619
  • 15
    Krambeck AE, Handa SE, Lingemann JE. Experience with more than 1,000 Holmium Laser Prostate enucleations for benign prostatic hyperplasia. J Urol 2010; 183: 11059
  • 16
    Kuntz R, Lehrich K, Ahyai S. Holmium laser enucleation of the prostate versus open prostatectomy for prostates greater than 100 grams: 5-year follow-up results of a randomised clinical trial. Eur Urol 2008; 53: 1606
  • 17
    Naspro R, Bachmann A, Gilling P et al. A review of the recent evidence (2006–2008) for 532-nm photoselective laser vaporisation and holmium laser enucleation of the prostate. Eur Urol 2009; 55: 134557