HOLMIUM LASER VERSUS TRANSURETHRAL RESECTION OF THE PROSTATE: A RANDOMIZED PROSPECTIVE TRIAL WITH 1-YEAR FOLLOWUP

0022-5'347B9/1625-1640/0

Vol. 162,1640-1644,November 1999 Printed in U.S.A.

THE JOLWALOF UrnCopyright 8 1999 by h r u w UEOLOOICAL ASSOCIATION,b c .

HOLMIUM LASER VERSUS TRANSURETHRAL RESECTION OF THE PROSTATE: A RANDOMIZED PROSPECTIVE TRIAL WITH 1-YEAR FOLLOWUP PETER J. GILLING,* MICHAEL MACKEY, MICHAEL CRESSWELL, KATIE KENNETT, JOHN N. KABALIN AND MARK R. FRAUNDORFER" From the Urology Department, Tauranga Hospital, Tauranga, New Zealand, and Urology Associates, Scottsbluff,Nebraska

ABSTRACT

Purpose: The high-powered ho1mium:YAG laser can be used for incision, ablation and resection of the prostate. The technique of holmium laser resection of the prostate is compared to transurethral prostatic resection for surgical management of benign prostatic hyperplasia in this prospective randomized study. Materials and Methods: A total of 120 urodynamically obstructed cases were randomized to holmium laser or transurethral prostatic resection. All eligible patients were assessed preoperatively and a t 3 weeks, and 3, 6 and 12 months postoperatively with an American Urologkal Association symptom score, peak urinary flow rate, and questionnaires concerning sexual function and continence. Preoperative pressure flow study, ultrasound prostate volume assessment and post-void residual volume measurement were repeated a t the 6-month visit. All complications were noted. Results: Holmium laser and transurethral resections resulted in significant improvements in symptom score, quality of life score, peak urinary flow rate and post-void residual urine measurements. Operating time was significantly longer in the holmium group but nursing contact time, catheter time and hospital stay were significantly less compared to the transurethral prostatic resection group. Urodynamic results were equivalent at 6 months. There were fewer side effects in the holmium group. Effects on continence, potency and symptoms were similar with 1-year followup. Conclusions: Holmium and transurethral resections of the prostate appear to be equivalent in surgical management of bladder outflow obstruction due to benign prostate hyperplasia. Perioperative morbidity was less in the holmium group. KEY WORDS: prostatic hyperplasia, prostatectomy, holmium, laser surgery, urodynamics The use of the high-powered (range 60 to 80 W.) holmium: flow rate 15 ml. per second or less, transrectal ultrasound YAG laser (2,140 nm.) has been reported for the incision, volume of the prostate less than 100 ml., post-void residual ablation and more recently resection of the human prostate urine volume less than 400 ml. and Schafer grade (or linearsince these lasers became commercially available in 1994.1-3 ized passive urethral resistance relation) 2 or greater. All This wavelength has also been used extensively for calculus patients had a digital rectal examination and serum prostate disease435 and other soft tissue applications.6-8 For surgical specific antigen (PSA) measured before enrollment, and management of benign prostatic hyperplasia (BPH) the tech- transrectal ultrasound guided biopsies were performed to nique of holmium laser prostatic resection has been shown to exclude from study cases of carcinoma of the prostate as be superior to visual laser ablation of the prostate with re- necessary. Catheterized patients and those who had underspect to catheter time, postoperative dysuria, flow rate meas- gone previous urethral or prostatic surgery were also exurements and urodynamic findings.9 Transurethral and hol- cluded from study. mium laser prostatic resections involve the acute resection of At enrollment the patients were evaluated by a complete prostate tissue which can be histologically examined, and medical history and physical examination, including digital recboth techniques produce a cavity in the prostatic fossa which tal examination, urinalysis and urine culture, PSA, AUA sympis similar in appearance. We compare the perioperative and tom score, single question quality of life score, sexual function postoperative course of 2 groups of urodynamically ob- assessment, continence assessment, ultrasound measurement structed cases randomly assigned to these treatments. of post-void residual, transrectal ultrasound measurement of prostatic volume and pressure flow urodynamic assessment, including peak urinary flow rate estimation (voided volume MATERIALS AND METHODS greater than 120 ml.). Consent was obtained from each patient. All candidates for surgical therapy for lower urinary tract Patients were randomized to transurethral (electrocautery symptoms and obstruction due to BPH at our institution group) or holmium laser (holmium group) prostatic resection were screened for possible inclusion in this study. Inclusion with a schedule balanced in blocks of 10. criteria were age 80 years or younger, American Urological Holmium laser resection of the prostate. All laser proceAssociation (AUA)symptom score 8 or greater, peak urinary dures were performed by 1 of 2 surgeons (P. J. G., M. R. F.) using our previously described technique.3 Maximum average power of 80 W. (2.0 J. at 40 Hz.) was used in each case. Accepted for publication May 14, 1999. General or spinal anesthesia was required in all cases. PostSu ported by Coherent Inc., Santa Clara, California. * Ikancial interest andor other relationship with Coherent Inc. operative bladder irrigation was only used if deemed neces1640

HOLMIUM LASER VERSUS TRANSURETHRAL RESECTION OF PROSTATE

sary by the surgeon. The catheter was removed the morning after surgery. Perioperative variables included estimated weight of resectable tissue, total energy used (kJ.), resection time, volume of irrigant used (1.1, actual weight of tissue retrieved (gm.), nursing contact time (minutes), catheter time (hours) and postoperative hospital stay (hours). Nursing time was stratified by category. Resection time was defined as the total time that the resectoscope sheath was in the urethra. All complications and adverse events were noted. Transurethral resection of the prostate. All resections were done by a urologist who had performed a minimum of 300 cases previously. A traditional transurethral prostatic resection was done in each case using a standard tungsten wire loop with a cutting current of 80 W. and a coagulating current of 160 W. General or spinal anesthesia was used. Parameters assessed were similar to those for holmium laser prostatic resection. Bladder irrigation was used in all cases postoperatively until hematuria diminished sufficiently and the catheter was removed before patient discharge from the hospital. There was no observed difference in the requirements for anesthesia between the 2 techniques. Postoperative evaluation commenced with a 21-day diary in which the patient graded urgency, frequency, hematuria and voiding discomfort each day using a simple Lickert scale (0-none, 1-mild, 2-moderate, 3-severe). An independent nurse investigator performed all postoperative assessments other than flexible cystoscopy. A daily score (out of 6) was obtained for the 2 questions relating to dysuria and voiding discomfort. All medications taken during this time were noted. The first clinic visit was 3 weeks postoperatively a t which time the diary was reviewed, and a flow rate test, AUA score, quality of life score and continence/potency assessment were performed. The patients were then evaluated at 3, 6 and 12 months when this assessment was repeated. If the AUA score or peak urinary flow rate value had not improved by at least 50% compared to baseline flexible cystoscopy was done. At the 6-month visit transrectal ultrasound, prostate volume and post-void residual measurements, and pressure flow urodynamic study were also performed. All adverse events were recorded. Groups were compared using independent t tests. AUA score, peak urinary flow rate and quality of life score from baseline to the different assessment times were compared using paired t tests. The outcome variables of post-void residual, detrusor pressure at maximum flow rate, all perioperative data and quality of life score were log transformed to normalize distributions before analysis. RESULTS

Patient population. Of 120 men 61 were randomized to undergo holmium laser prostatic resection and 59 transurethral prostatic resection. Baseline patient characteristics in each group are listed in table 1. There was no significant

.-

difference between the 2 groups for any parameter at baseline. Of the 120 patients 102 completed the 12-month assessment. Patients did not complete this assessment due to death from cardiovascular or malignant disease (1 in holmium and 1in electrocautery group, respectively), or because they were lost to followup (6 in holmium and 5 in electrocautery group) or required reoperation (1in holmium and 4 in electrocautery group). Patients were lost to followup for reasons including development of intercurrent illness, moving from the area and unwillingness to return t o the clinic. Perioperative outcome (table 1).A mean total of 110.02 kJ. (range 28.4 to 388.0) of energy was used in the holmium group. Only 1 patient in this group (1.6%) required postoperative bladder irrigation due to the degree of observed hematuria at the completion of the procedure. Mean catheter time plus or minus standard deviation was significantly longer in the electrocautery group at 37.2 % 15.92 hours (range 13.2 to 90.7) compared to 20.0 2 11.39 (range 11.8to 96.2) in the holmium group (p <0.001). Mean postoperative hospital stay was also significantly longer in the electrocautery group at 47.5 5 17.37 hours (range 19.9 to 98.3) compared to the holmium group at 26.2 % 11.71 (range 16.2 to 96.2) (p <0.001). Carcinoma of the prostate was found in 7 patients (0.06%) in the study population all of whom were in the electrocautery group. Poorly differentiated transitional cell carcinoma was found in another patient undergoing transurethral prostatic resection who subsequently underwent cystoprostatectomy. Patient diary. Analgesia of some kind was required by 46% of the holmium versus 50% of the transurethral prostatic resection group for urinary symptoms in the first 3 postoperative weeks. These medications included urinary alkalizers, mild analgesics and nonsteroidal anti-inflammatory drugs. There was no observed difference between the 2 groups in the type of analgesia required. There was no significant difference in the severity of painful urinary symptoms (voiding discomfort and dysuria) whether analyzed as an overall (0.43 versus 0.54) or separate score for each group in the first 3 weeks. The degree of hematuria was significantly less in postoperative week 1 following holmium laser prostatic resection compared to transurethral prostatic resection (p <0.01) but this difference disappeared in weeks 2 and 3. Followup data. Comparative data for the 2 groups at 3 weeks, and at 3, 6 and 12 months postoperatively are presented in table 2. There was a highly significant improvement (p <0.001) compared to baseline for each parameter at all intervals in both groups. At 6 months post-void residual urine was 26.7 ml. (range 0 t o 245) in the holmium and 34.3 (range 0 to 295) in the electrocautery group. Transrectal ultrasound volumes decreased t o 29.3 ml. (range 11 to 61) in the holmium and 27.3 (range 10 t o 75) in the electrocautery

TABLE1. Baseline characteristics and perioperative data

of

the 2 groups

Mean 2 SD (range) p Value

~

~.

1641

Holmium Group

Electrocautery Group

66.9 i 6.5 (47-781 44.3 i 19.0 (11-92) 87.8 i 88.4 (0-346) 8.9 2 3.0 (3-14) 21.9 2 6.2 (10-35) 75.9 ? 26.2 (39-1491 21.7 i 20.9 12-120) 41.5 2 23.1 (16-108) 7.9 1 6 . 1 (0.7-32) 15.8 5 9.3 (3-50) 0.67 i 4.9 1CL38) 36.1 ? 26.7 (11-174)

66.8 % 7.4 (36-80) 44.6 ? 20.7 (11.5-95) 84.7 2 81.7 (0-373) 9.1 2 3.2 (3-14) 23.0 ? 5.9 19-35) 83.4 i 27.9 (43-1431 15.5 i- 11.6 13-50, 25.3 2 14.7 (8-68) 14.5 2 11.7 i2.2-47.41 10.0 i 6.5 (3-28) 28.2 i 15.9 (8-70) 105.6 i 116.5 (38-665)

~~

Pt. age (yrs.) Transrectal ultrasound vol. (ml.) Residual vol. (ml.) Peak urinary flow rate iml./sec.) AUA score Detrusor pressure at max. flow (cm. water) Estimated resection wt. (gm.) Resection time imins.) Tissue retrieved (gm.) Intraop. irrigant (I.) Postop. irrigant (1.) Nursing contact time tmins.)

0.89 0.93 0.85 0.81 0.32 0.13 10.05 <0.001 <0.001 10.05 <0.001 <0.001

1642

HOLMIUM LASER VERSUS TRANSURETHRAL RESECTION OF PROSTATE TABLE 2. Comparison of AUA score, peak urinary flow rate and quality of life score values Parameter

PreOp. No. pts. 120 Mean AUA score t- SD (range): 21.9 1- 6.2 (10-35) Holmium 23.0 t 5.9 (9-35) Electrocautery 0.32 p Value Mean mlhec. peak urinary flow rate 5 SD (range): Holmium 8.9 2 3.0 (3-14) Electrocautery 9.1 2 3.2 (3-14) p Value 0.81 Mean quality of life score 2 SD (range): Holmium 4.5 f 1.1 (3-6) Electrocautery 4.7 f 1.1 (3-6) p Value 0.45

3 Wks. Postop. 120

3 Mos. Postop. 111

6 Mos. Postop.

7.7 f 5.0 (0-24) 7.7 t- 5.3 ( 0 3 0 ) 0.99

5.6 2 5.1 (0-25) 5.7 t 5.2 (0-30) 0.88

3.8 t- 3.8 (0-24) 5.0 t 4.5 (0-23) 0.17

4.2 2 6.0 (0-29) 4.3 t- 4.1 (0-16) 0.92

22.8 t- 10.0 (6-50) 20.2 f 9.5 (6-50) 0.16

23.9 ? 8.7 (7-50) 22.4 2 9.0 (8-43) 0.35

25.2 2 11.9 ( 6 6 3 ) 20.4 t- 8.5 (6-44) <0.05

1.1 2 1.3 (0-6) 1.5 t- 1.4 (0-6) 0.11

0.88 t- 1.4 (0-6) 1.6 ? 1.5 (0-6) c0.05

21.0 t 8.9 (2-50) 22.4 2 10.0 (5-43) 0.42 1.7 t 1.3 (0-5) 1.7 2 1.3 (0-6) 0.75

.150

1

A 0 A

(04)

(0-6)

0.60

12 Mos. Postop. 102

preoperatively. At 12 months 4 patients in the holmium group (8.3%)and 5 in the electrocautery group (10.6%)had deterioration in the level of potency compared to the preoperative level. Interestingly, the level of potency improved in 10 patients in the holmium group (20.1%)and 9 in the electrocautery group (19.1%)during the same period. Of the sexually active patients 24 of 25 (96%)in the holmium and 32 of 37 (86%)in the electrocautery group had retrograde ejaculation. The adverse events are listed in table 3. The single death in the holmium group was due to a myocardial infarction 8 days following uncomplicated surgery. The death in the electrocautery group occurred 3 weeks after radical cystoprostatectomy for poorly differentiated transitional cell carcinoma. Reoperations consisted of 1 bladder neck incision in the holmium group, and 2 bladder neck incisions and 2 revision prostatectomies in the electrocautery group.

group. There was no significant difference between the 2 groups for either parameter. Urodynamic findings at 6 months. All cases were urodynamically obstructed (Schafer grade 2 or greater) a t baseline. Mean detrusor pressure at maximum flow rate decreased from 75.9 cm. water (range 39 to 147) preoperatively to 35.2 (range 15 to 99) at 6 months in the holmium group and from 83.4 (range 43 to 143) preoperatively to 39.2 (range 13 to 77) a t 6 months in the electrocautery group. Schafer grade (linearized passive urethral resistance relation) decreased from a mean of 3.5 (range 2 to 6) preoperatively to 0.7 (range 0 to 3) a t 6 months in the holmium group and from 3.6 (range 2 to 6) to 1.2(range 0 to 4) in the electrocautery group. There was no significant difference between the 2 groups at 6 months for either parameter. Urodynamic findings are depicted on the International Continence Society nomogram (see figure).lO Continence, potency and adverse events. Preoperatively 56% patients reported some degree of urinary incontinence. At 12 months 1 holmium group patient and 2 electrocautery group patients required pads for urinary leakage, all of whom had some leakage preoperatively. Overall 46% of the patients had erections that were insufficient for intercourse

a

1.4 t- 1.5 1.6 5 1.4

106

DISCUSSION

The holmium laser is a pulsed laser with a wavelength in the near infrared spectrum (2,140nm.). High-powered (range 60 to 80 W.) systems have been commercially available since

A

A

E

Pre-operative HoLRP Pre-operative TURP

I A TURP 6 Months

A

I

100

50 " 0

01 0

I

5

O O A

A A

0

O

O

0

I

I

I

25

30

35

- - _ ,. -unobstructed "

10

15

20

Maximum Flow rate (Qmax) ml/s International Continence Society nomogram of urodynamic findings. HoLRP, holmium laser prostatic resection. TURP, transurethral prostatic resection.

HOLMIUM LASER VERSUS TRANSURETHRAL RESECTION OF PROSTATE TABLE3. Adverse events in each group at 12 months postoperatively Adverse Event

Blood transfusion Recatheterized Reoperation (any) Urinary tract infection Strictures: SubmeataVmeatal Bulbadpenile Deep vein thrombosis Deaths Totals

No. Holmium (%)

No. Electrocautery (%)

0 5 (8.2) l(1.6) 3 (4.9)

4 (6.6) 8 (13.1) 4 (6.6) 5 (8.2)

4 (6.6) 2 (3.3) 0

5 1 1 1

1(1.6) I6

(8.2) (1.6) (1.6) (1.6)

29

1994 and have expanded the range of soft tissue indications t o include endoscopic resection of the prostate.3.11,12 The technique of holmium laser prostatic resection differs from that of traditional transurethral prostatic resection in that the adenoma is dissected off of the surgical capsule retrograde. The apex is defined before resection of the lateral lobes commences. Dissection occurs precisely in the plane between adenoma and capsule, and bleeding points are coagulated with the defocused beam as they are encountered. Therefore, a potential drawback of this procedure is that it is a dissection involving the surgical planes of the prostate and, thus, has a learning curve and requires skill in endoscopic techniques. The hemostatic nature of this wavelength is responsible for many of the perioperative advantages of holmium laser compared to transurethral prostatic resection, including the decrease in nursing contact time, irrigating fluid requirement, blood transfusion, catheter time and hospital stay. It also enables the resection to be precise as landmarks, such as the surgical capsule and apex, are clearly identifiable. Operating (resection) time was significantly longer in the holmium than in the electrocautery group, which is primarily due to the time-consuming process of dividing the lobes into fragments with the laser which can safely be removed through the urethra. This drawback has largely been overcome by further evolution in the technique which includes complete enucleation of the median and both lateral lobes intact, and development of a transurethral soft tissue morcellator.13.14 Prostates of any size can now be approached transurethrally using these techniques in a timely manner with perioperative morbidity similar to holmium laser prostatic resection. The known holmium laser properties and increased resection time result in a significant amount of tissue vaporization, which accounts for the difference in retrieved tissue weight between the 2 groups and part of the observed discrepancy between the numbers of patients in each group who had cancer of the prostate. An increased amount of thermal artifact is also present in the tissue retrieved in the holmium compared to the electrocautery group (unpublished data). The tissue loss to vaporization plus the increased thermal artifact likely explain the difference in the numbers of stage A cancers between the groups as all patients were screened preoperatively with digital rectal examination and PSA (and transrectal ultrasound when necessary). This problem has also been largely obviated by development of a transurethral mechanical tissue morcellation which has no thermal component. Also, because of the increased efficiency of this process compared t o the resection technique considerably less laser energy is required per gm. tissue removed.14 Urodynamic findings, prostate volume measurements at 6 months and peak urinary flow rate measurements throughout followup confirm that a similar amount of tissue is being removed with the 2 techniques, despite the discrepancy between pathological tissue weights. This tissue is removed acutely at surgery and, therefore, patients experience an immediate improvement in symptoms and flow rate unlike

1643

earlier forms of laser prostatectomy. The incidence of painful voiding symptoms in the early postoperative period is also similar with the 2 techniques which has overcome a further concern associated with neodymium:YAG coagulation prostatect~my.~ The reported stricture rate in each group (9.9 and 9.8%)is largely due to the fact that patients with less than 50% improvement in flow rate or symptom score compared to baseline underwent flexible cystoscopy. Therefore, the clinically significant stricture rate is overestimated. The Agency for Health Care Policy and Research guidelines based on 12,003 cases suggests a stricture rate of 3.1% (range 0.5 to 9.7) as typical15 but well documented contemporary series with rates as high as 16.3%have been reported.16 Although the transfusion rate of 6.6% in the electrocautery group is within the 5 to 10% range which is currently expected,15 rates as low as 1%have been reported.17 All of the transfusions in the series were clinically indicated due to hemodynamic compromise of the patients. In 2 patients bleeding at the end of the procedure was minimal and significant hemorrhage developed subsequently. In conclusion, holmium laser prostatic resection takes longer to perform than standard transurethral prostatic resection but perioperative factors, including nursing contact time, transfusion rate, catheter time and hospital stay, favor the holmium procedure. Urodynamic findings, symptom assessment, continence and potency are equivalent at l year. Dr. Chris Frampton provided statistical input.

REFERENCES

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HOLMIUM LASER VERSUS TRANSURETHRAL RESECTION OF PROSTATE

tion: an update on the early clinical experience. J. Endourol., 12: 457, 1998. 15. McConnell, J. D., Barry, M. J., Bruskewitz, R. C., Bueschen, A. J., Denton, S. E., Holtgrewe, H. L., Lange, J. L., McClennan, B. L., Mebust, W. K., b i l l y , N. J., Roberts, R. G., Sacks, S. A. and Wasson, J. H.: Clinical Practice Guideline for Benign Prostatic Hyperplasia: Diagnosis and Treatment. Rockville, Maryland: Agency for Health Care Policy and Research, Public Health Service, publication No. 94-0582,1994.

16. Meyhoff, H. H., Nordling, J. and Hald, T.: Urodynamic evaluation of transurethral vs transvesical prostatectomy. A randomised study. Scand. J. Urol. Nephrol., 1 8 27,1984. 17. Wasson, J. H., Reda, D. J., Bruskewitz, R. C., Elinson, J., Keller, A. M. and Henderson, W. G. for the Veterans Affairs Cooperative Study Group on Benign Prostatic Hyperplasia: A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. New Engl. J. Med., 332 75,1995.