UroToday - European Urology - A Randomised Trial Comparing Holmium Laser Enucleation Versus Transurethral Resection in the Treatment of Prostates Larger Than 40Grams: Results at 2 Year

European Urology - A Randomised Trial Comparing Holmium Laser Enucleation Versus Transurethral Resection in the Treatment of Prostates Larger Than 40Grams: Results at 2 Year

Tuesday, 05 September 2006

Volume 50, Issue 3, Pages 569-573 (September 2006)

1. Introduction

The surgical management of men with large prostates (>40g) that cause bladder outflow obstruction (BOO) secondary to benign prostatic hyperplasia (BPH) is a challenging area.
Traditional treatment such as transurethral electrocautery resection of the prostate (TURP) has increased risks of bleeding and TUR syndrome [1] when treating the larger prostate, and it is generally contraindicated for glands >100g. These glands have often been treated with the more significant procedure of open prostatectomy, which often exposes elderly patients to increased perioperative morbidity.

The holmium laser, with a wavelength of 2,140nm, conducts through saline and maintains the ability to precisely incise prostatic tissue, and has excellent haemostatic properties. This minimises the risks of perioperative bleeding and TUR syndrome, which are significant concerns when performing TURP. Holmium laser resection of the prostate (HoLRP) is as effectifve as TURP in the management of BOO and has less perioperative morbidity than TURP [2], [3], [4]. This procedure has been further refined with the development of the soft tissue morcellator to allow enucleation of whole lobes of the prostate. Holmium laser enucleation of the prostate (HoLEP) can treat any prostate size, with minimal risk of TUR syndrome because saline rather than iso-osmolar electrolyte-free irrigating solution is used. Transfusion rates are also extremely low.

To address the durability of HoLEP, this study reports the medium-term data from a randomised clinical trial that compared the postoperative outcomes of men with large prostates (40–200g on ultrasound) that caused BOO, who underwent HoLEP compared to those who underwent TURP [5].

2. Patients and methods

2.1. Participants

After ethical approval was obtained, all patients who presented to the urology service at Tauranga Hospital between June 1997 and December 2000 and considered for surgical treatment for BOO secondary to BPH were invited by an independent research nurse to participate in this trial. At enrolment all patients were thoroughly evaluated by medical history and physical exam, digital rectal exam, prostate-specific antigen (PSA), urinalysis and urine culture, American Urological Association (AUA) symptom score, single question Quality of Life (QoL) score, transrectal ultrasound (TRUS) measurement of prostatic volume, post-void residual assessment (PVR), maximum urinary flow rate (Q_max) and pressure flow urodynamic assessment.

Inclusion criteria were TRUS volume of 40–200g, Q_max of 15ml/s or less, AUA symptom score of 8 or greater, PVR of less than 400ml, and urodynamic Schaffer grade 2 or greater. TRUS biopsies were performed to exclude cases of prostatic carcinoma. Catheterised patients and those with a history of previous urethral or prostatic surgery were excluded.

2.1.1. HoLEP

All procedures were performed by one of two surgeons (PJG or MRF), who used the technique previously described [6]. Maximum power was set at 100W for each case and a Versacut morcellator (Lumenis, Inc., Tel Aviv, Israel) was used. Post-operative Foley catheter irrigation was performed if deemed necessary; most patients were treated with a standard Foley catheter, which was normally removed the day after surgery.

2.1.2. TURP

Standard TURP was performed with a tungsten cutting wire at 160W cutting and 80W coagulating current by one of three surgeons (PJG, MRF, AMW), all of whom had performed more than 500 TURPs. An irrigating Foley catheter was inserted and bladder irrigation was used as necessary until haematuria had settled sufficiently to remove the catheter.

2.2. Outcomes

2.2.1. Primary outcomes

Post-operative primary outcomes were AUA symptom scores, QoL score, and Q_max at one, three, six, 12, and 24 months.

2.2.2. Secondary outcomes

Secondary outcomes included a pressure flow urodynamic assessment, PVR, and TRUS volume measurement at six months of follow-up. Continence and potency were assessed with a questionnaire that involved standard questions that we have employed in each of our studies over the last 10 years [2], [5]. These predated current standardised questionnaires, but are useful in that they allow internal comparison. Continence questions involved separate questions about stress, urge, and overflow incontinence, and post-void dribbling. Re-operation and recatheterisation rates were recorded and patients with less than 50% improvement in Q_max or symptom score had flexible cystoscopy to ensure the absence of urethral strictures.

A sample size calculation that used α=0.05 and β=0.20 based on previous work [2] showed that 30 individuals would be required per group to show a 10% difference. A balanced blocked randomisation schedule (block of six patients) was used to allocate patients to one or the other treatment arm. Any patient who met the inclusion criteria was allocated the next available envelope and allocated accordingly to a treatment arm. If the patient refused to participate in the study, his envelope was not reused. Data distribution for all primary and secondary outcomes did not fit with standard normality assumptions, so the two procedures were compared with a non-parametric Mann-Whitney U test.

3. Results

3.1. Baseline data

Sixty-one men participated in this study: 31 in the HoLEP arm and 30 in the TURP arm. Table 1 shows the preoperative patient characteristics of each arm. There was no significant difference between the two groups. One patient from the HoLEP arm died preoperatively, which left 30 in each arm of the study. A total of 48 patients reached the 24 month follow-up, 26 following TURP and 22 following HoLEP. Four patients were lost to follow-up between 12 and 24 months. One died and three could not be contacted.

Table 1. Baseline patient characteristics


	Mean±SE HoLEP^a (range)	Mean±SE TURP^a (range)
Age (range)	71.7±1.1 (54–84)	70.3±1.0 (59–83)
AUA^a Symptom Score	26.0±1.1 (14–35)	23.7±1.2 (9–35)
QoL^a Score	4.8±0.2 (2–6)	4.7±0.2 (2–6)
Qmax^a (ml/s)	8.4±0.5 (2–14)	8.3±0.4 (3–12)
TRUS^a vol (cc)	77.8±5.6 (42–152)	70.0±5.0 (46–156)
PdetQmax (cmH20)	76.2±4.4 (44–137)	85.8±5.4 (46–156)
Schaffer Grade	3.5±0.2 (2–6)	3.7±0.2 (2–6)

^a HoLEP: holmium laser enucleation of the prostate; TURP: transurethral resection of the prostate; AUA: American Urological Association; QoL: Quality of Life; Qmax: maximum urinary flow rates; TRUS: transrectal ultrasound

3.2. Outcomes

Perioperative data and flow diagram out to 12 months have been previously published [5]. This showed that HoLEP was superior to TURP with respect to catheter time and hospital stay, but took longer to perform. However, significantly more tissue was removed by HoLEP than TURP.

3.3. Primary outcome data

The primary outcome data at one, three, six, 12, and 24 months are shown in Table 2. There was no difference in post-operative Q_max, AUA, or QoL scores between the two groups at six, 12, and 24 months.

Table 2. Post–operative data


	HoLEP	TURP
1 month (n=60)
AUA	8.6±1.2	5.7±1.1^*
QoL	2.7±0.4	1.6±0.3
Q_max (ml/s)	22.3±2.3	18.4±1.6

3 months (n=56)
AUA	4.8±0.8	2.4±0.9
QoL	1.8±0.4	1.9±0.6
Q_max (ml/s)	24.2±1.7	18.9±1.9^*

6 months (n=54)
AUA	6.0±1.0	4.8±0.7
QoL	1.6±0.3	1.5±0.2
Q_max (ml/s)	21.3±2.1	18.9±2.8

12 months (n=52)
AUA	4.6±0.7	4.7±0.9
QoL	1.5±0.5	1.4±0.3
Q_max (ml/s)	21.3±2.1	18.9±2.8

24 months (n=48)
AUA	6.1±1.0	5.2±0.8
QoL	1.25±0.2	1.25±0.2
Q_max (ml/s)	21.0±2.0	19.3±2.2

^* p<0.05.

3.4. Secondary outcome data

Secondary outcome data are shown in Table 3.

Table 3. Data at six months post-procedure (including pre-op. PdetQmax)


	HoLEP	TURP
PVR^* (mls)	33.7±5.5	51.8±14.5
TRUS vol (ml)	28.4±1.8^**	46.6±4.4
PdetQmax (cmH20) preop	73.2±4.4	85.8±5.4
PdetQmax (cmH20) 6 mos	20.8±2.8^**	40.7±2.7
Schaffer Grade	0.2±0.09^**	1.2±0.2

^* PVR: post-void residual.

^** p<0.001.

In the 18 TURP patients who had complete PSA data before and after, a 65% reduction was seen (a mean of 5.2micromol/l to 2.3micromol/l) and in the 10 HoLEP patients with PSA measured post-operatively in 87% reduction was noted: (8.7micromol/l to 1.2micromol/l).

There was no significant difference in post-operative PVR between the two groups. However, there were statistically significant differences in favour of HoLEP with regard to improvements in post-operative TRUS volume, PdetQmax, and Schaffer Grade at six months of follow-up.

3.5. Continence and potency

Forty-three percent of HoLEP patients and 39% of TURP patients had potency sufficient for intercourse pre-operatively. At 12 months, two patients had improved potency (3.9%) and two (3.9%) had deterioration in potency. At 24 months, two patients in each group had new onset of erectile dysfunction (erections insufficient for penetration) compared to their pre-operative state. Retrograde ejaculation was seen in 12 of 16 patients in the Holmium group and eight of 13 in the TURP group.

Incontinence was present in 48% of HoLEP patients and 38% of TURP patients pre-operatively (not including post-micturition dribbling). Six of the 15 incontinent patients in the HoLEP group and eight of 11 in the TURP groups regained continence post-operatively. Only one patient (in the HoLEP group) had new onset stress incontinence noted at 12 months, which had resolved by 24 months. One patient in the TURP group had urge incontinence at 24 months that did not require protection.

3.6. Adverse events

Adverse events at 24 months are documented in Table 4. Similar numbers required recatheterisation in the two groups. One TURP patient required blood transfusion. Aside from recatheterisation, the only other adverse event in the HoLEP group was a urethral stricture that required dilatation in the office. Three patients in the TURP group developed strictures.

Table 4. Total adverse events at 24 months


	HoLEP	TURP
Blood transfusion	–	1
Re-catheterisation	5	4
Re-operation	–	2
Documented urinary tract infections	–	2
Strictures	1 (submeatal)	3 (2 submeatal, 1 bulbar)
Deaths	–	1 at 15 months post-op

4. Discussion

Many treatments have been offered as alternatives to TURP. Most have not approached TURP with respect to durability or efficacy, although morbidity is often improved. In men with larger prostates, the alternatives are even more limited. The characteristics of the holmium laser wave length determine its versatility and provide an endoscopic alternative to both TURP and open prostatectomy when used for enucleation [6].

In our study, HoLEP was equivalent to TURP with respect to symptom score improvement, QoL improvement, and Q_max at 24 months of follow-up, although two TURP patients required re-operation. This study also demonstrated that HoLEP was superior with regard to perioperative morbidity, with reduced bladder irrigation and catheter times and reduced hospital stay, even though more prostate tissue was retrieved [5].

The goal of this paper is to demonstrate HoLEP's medium-term durability compared to TURP. TRUS volume reduction post-operatively is superior, and urodynamic relief of obstruction is greater; thus, HoLEP is likely to be at least as effective as TURP in long-term follow-up.

HoLEP has been proven to be a valid alternative in small (<40g) [7], large (>40g) [8], [9], [10], [11], and very large [12] (>100g) prostates compared to TURP or open prostatectomy. Kuntz et al., in a well-designed study, demonstrated reduced perioperative morbidity for HoLEP compared to open prostatectomy, with equal outcome measures [12]. Gilling et al. [2] demonstrated similar findings when they compared HoLRP with TURP for smaller glands. There is potentially no limit to the size of a prostate that can be treated with HoLEP [13]; the largest gland treated in our institution is 450g and open prostatectomy has been eliminated.

Two issues, apart from appropriate marketing, prevent HoLEP from rapidly becoming a more widespread procedure: the learning curve and the financial outlay. The learning curve [14] can be minimised with appropriate case selection and a short period of structured supervision. Anecdotally, the opinion of our trainees is that the anatomical nature of enucleation makes it inherently easier to master than TURP. The initial outlay for a holmium laser is significant, but a previous study at our institution [15] demonstrated that HoLRP was cost effective compared to TURP. The multi-use nature of the holmium laser for stones and other soft tissue applications further improves its cost effectiveness.

The only other minimally invasive procedure that may challenge HoLEP is laparoscopic retropubic prostatectomy [16]. In this recent series from Brazil, the mean prostate size was 144g on ultrasound, the catheter time was 4.6 days, and the hospital stay 3.5 days. In a contemporary HoLEP series the prostate size was greater and the operative, hospital, and the catheter times were significantly shorter [17]. Individual expertise will likely determine which approach for enucleation is employed, but the transurethral route (HoLEP) appears superior in comparable series in every respect.

No case of TUR syndrome was seen in either group. None would be expected in the HoLEP arm as normal saline is the irrigant; however, 26% of patients do absorb a mean of 459ml of fluid [18]. The incidence of TUR syndrome is slight in modern TURP series.

5. Conclusions

HoLEP is an efficient technique performed with a versatile energy source. It represents a paradigm shift in the endoscopic management of BPH and can be used to treat prostates of all sizes. This study addresses the question of durability of HoLEP and suggests that it will be at least as durable as TURP in the long term as more tissue is surgically removed and by 24 months fewer re-operations were required.

References

1. Mebust WK, Holtgrewe HL, Cockett AT, Peters PC. Transurethral prostatectomy: immediate and postoperative complications. A cooperative study of 13 participating institutions evaluating 3,885 patients. J Urol. 1989;141:243–247.

2. Gilling PJ, Mackey M, Cresswell M, Kennett KM, Kabalin JN, Fraundorfer MR. Holmium laser resection V transurethral resection of the prostate: results of a randomized trial with 1 year of follow-up. J Urol. 1999;162:1640–1644.

3. Gilling PJ, Kennett KM, Fraundorfer MR. Holmium laser resection V transurethral resection of the prostate: results of a randomized trial with 2 years of follow-up. J Endourol. 2000;14:757–760.

4. Westenberg A, Gilling P, Kennett KM, Frampton C, Fraundorfer MR. Holmium laser resection of the prostate versus transurethral resection of the prostate: results of a randomized trial with 4-year minimum long-term followup. J Urol. 2004;172:616–619.

5. Tan AHH, Gilling PJ, Kennett KM, Frampton C, Westenberg AM, Fraundorfer MR. A randomized trial comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200grams). J Urol. 2003;170:1270–1274.

6. Gilling PJ, Kennett KM, Das AK, Thompson D, Fraundorfer MR. Holmium laser enucleation of the prostate (HoLEP) combined with transurethral tissue morcellation: an update on the early clinical experience. J Endourol. 1998;12:457–459.

7. Aho TF, Gilling PJ, Kennett KM, Westenberg AM, Fraundorfer MR, Frampton C. Holmium laser bladder neck incision versus holmium enucleation of the prostate as outpatient procedures for prostates less than 40 grams: a randomized trial. J Urol. 2005;174:210–214.

8. Montorsi F, Naspro R, Salonia A, et al.. Holmium laser enucleation versus transurethral resection of the prostate: results from a 2-center, prospective, randomized trial in patients with obstructive benign prostatic hyperplasia. J Urol. 2004;172:1926–1929.

9. Kuntz RM, Ahyai S, Lehrich K, Fayad A. Transurethral holmium laser enucleation of the prostate versus transurethral electrocautery resection of the prostate: a randomized prospective trial in 200 patients. J Urol. 2004;172:1012–1016.

10. Gupta N, Sivaramakhrisna , Kumar R, Dogra PN, Seth A. Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing benign prostatic hyperplasia of >40g. BJU Int. 2006;97:85–89.

11. Tooher R, Sutherland P, Costello A, Gilling PJ, Rees G, Maddern G. A systematic review of holmium laser prostatectomy. J Urol. 2004;171:1773–1781.

12. Kuntz R, Lehrich K, Ahyai S. Transurethral holmium laser enucleation of the prostate compared with transvesical open prostatectomy: 18-month follow-up of a randomized trial. J Endourol. 2004;18:189–191.

13. Elzayat EA, Elhilali MM. Holmium laser enucleation of the prostate (HoLEP): the endourologic alternative to open prostatectomy. Eur Urol. 2006;87–91(Epub 2005;Nov 2).

14. El-Hakim A, Elhilali MM. Holmium laser enucleation of the prostate can be taught: the first learning experience. BJU Int. 2002;90:863–869.

15. Fraundorfer M, Gilling P, Kennett KM, Dunton NG. Holmium laser resection of the prostate is more cost effective than transurethral resection of the prostate: results of a randomized prospective study. Urology. 2001;57:454–458.

16. Mariano MB, Tefilli MV, Graziottin TM, Morales CMP, Goldraich IH. Laparoscopic prostatectomy for benign prostatic hyperplasia – a six year experience. Eur Urol. 2006;49:127–132.

17. Matlaga BR, Kim SC, Kuo RL, Watkins SL, Lingeman JE. Holmium laser enucleation of the prostate for prostates of >125mL. BJU Int. 2006;97:81–84.

18. Shah HN, Kausik V, Hedge S, Shah JN, Bansal MB. Evaluation of fluid absorption during holmium laser enucleation of prostate by breath ethanol technique. J Urol. 2006;175:537–540.

Liam C. Wilson^a, Peter J. Gilling^a, Andrew Williams^a, Katie M. Kennett^a, Chris M. Frampton^b, Andre M. Westenberg^a, Mark R. Fraundorfer^a ^a Department of Urology, Tauranga Hospital, Tauranga, New Zealand
^b Department of Biostatistics, Christchurch School of Medicine, Christchurch, New Zealand

Accepted 11 April 2006 published online 2 May 2006.
doi:10.1016/j.eururo.2006.04.002

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