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

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].

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 HoLEPa (range)	Mean±SE TURPa (range)
	Age (range)	71.7±1.1 (54–84)	70.3±1.0 (59–83)
	AUAa Symptom Score	26.0±1.1 (14–35)	23.7±1.2 (9–35)
	QoLa Score	4.8±0.2 (2–6)	4.7±0.2 (2–6)
	Qmaxa (ml/s)	8.4±0.5 (2–14)	8.3±0.4 (3–12)
	TRUSa 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.

3.3. 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 Qmax, 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
	Qmax (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
	Qmax (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
	Qmax (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
	Qmax (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
	Qmax (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.

3.6. 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 Qmax 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.