A Multicenter Study on the Efficacy and Safety of Interstitial Laser Coagulation Versus a-Blockade in Subjects With Symptomatic Benign Prostatic Hyperplasia: Preliminary Results
ILC in the Treatment of BPH
ILC IN THE TREATMENT OF BPH A Multicenter Study on the Efficacy and Safety of Interstitial Laser Coagulation Versus -Blockade in Subjects With Symptomatic Benign Prostatic Hyperplasia: Preliminary Results Michael K. Brawer, MD Northwest Prostate Institute, Northwest Hospital, Seattle, WA Significant efforts have been made to develop minimally invasive surgical approaches to the treatment of benign prostatic hyperplasia, both to lessen the morbidity of the standard operative procedures and to avoid the need for continued drug therapy throughout the patient’s life. Interstitial laser coagulation (ILC) is a minimally invasive procedure that can be performed with local, regional, or general anesthesia. With this operator-dependent procedure, the surgeon can selectively control placement of the laser fiber to achieve the optimum destruction of tissue. Preliminary (6-month) data from a randomized trial comparing -blockade with ILC demonstrate that treatment with ILC is associated with a clinically significant decrease in American Urological Association symptom scores, a result superior to that achieved with an -blocker. [Rev Urol. 2005;7(suppl 9):S29-S33] © 2005 MedReviews, LLC Key words: Benign prostatic hyperplasia • Lower urinary tract symptoms • Interstitial laser coagulation • -Blockers • American Urological Association symptom score enign prostatic hyperplasia (BPH) with resulting lower urinary tract symptomatology (LUTS) is a universal consequence of aging. Historically, a large percentage of men with bothersome LUTS have remained untreated because surgery, primarily transurethral resection of the prostate (TURP), has been the only available approach. Over the last 3 decades, pharmacologic approaches B VOL. 7 SUPPL. 9 2005 REVIEWS IN UROLOGY S29 ILC Versus -Blockade for BPH continued to the management of LUTS resulting from BPH have emerged as the firstline therapeutic options. The success of -adrenergic blockade began with nonspecific -blockers, such as prazosin. Long-acting agents, such as terazosin and doxazosin, entered widespread use, and, subsequently, the more prostate-specific agents, such as tamsulosin and alfuzosin, have been widely accepted by both urologists and primary care practitioners as initial therapy for symptomatic men. The 5-reductase inhibitors, including finasteride and dutasteride, although less effective in terms of symptom reduction, have been shown to be therapeutic for men with large prostates and have been noted particularly to delay the progression of LUTS. Minimally Invasive Therapy for BPH Despite the success of pharmacologic approaches, there have been significant efforts to develop minimally invasive approaches, which would at once lessen the morbidity of the standard operative procedures and avoid the need for continued drug therapy throughout the patient’s life. These therapies have primarily used thermal energy to destroy obstructive prostatic tissue. Treatment approaches include transurethral microwave thermal therapy (TUMT), transurethral needle ablation, high-intensity focused ultrasound, laser vaporization, and interstitial laser coagulation (ILC). Each of these approaches has been claimed to be successful, but unfortunately there have been few head-tohead comparisons among them. Kursh and associates1 reported on a multicenter investigation of 72 men treated with either TURP (n 35) or ILC (n 37). The patients were followed up for 2 years. Patients undergoing TURP had a slightly increased median peak urinary flow rate (Qmax) S30 VOL. 7 SUPPL. 9 2005 (16.5 vs 13.9 mL/s); however, this did not achieve statistical significance. Symptom indexes and quality of life were similarly improved in both groups. Six of the patients treated with ILC subsequently received TURP. There was reduction in sexual function in patients undergoing TURP but no effect from ILC. American Urological Association (AUA) symptom scores decreased 6 points in the TURP cohort and 7 points in those undergoing ILC at 6 months. At 24 months, the diminution from baseline and median symptom score was 7 versus 9, favoring TURP. Interstitial Laser Coagulation Interstitial laser coagulation is a minimally invasive thermotherapy to treat BPH. This procedure can be performed with local, regional, or general anesthesia. The Indigo® Optima laser fiber (Ethicon Endo-Surgery, Cincinnati, OH) is introduced into the prostatic tissue transurethrally, and laser energy is introduced to raise the temperature of prostatic tissue to 85°C. This is an operator-dependent procedure, and the surgeon can selec- tively control placement of the laser fiber to achieve the optimum destruction of tissue. There is minimal injury to the urothelium; thus, irritative symptoms are minimized. Coagulative necrosis results in a significant decrease in prostate volume, which occurs over several months. The postoperative catheterization period with ILC is shorter than that of visual laser ablation of the prostate, in which patients experience prolonged irritative voiding symptoms and urinary retention, lasting for weeks and even months (see also the article by Muta M. Issa, MD, in this publication). In a recent review of the world literature,2 785 patients who had undergone ILC were identified from 14 series. Follow-up ranged from 2 to 12 months. The overall AUA symptom score improvement was 70% (scores decreasing from 22.8 to 6.8), ranging between 32% and 92% in individual series. Improvement was also noted in Qmax, almost doubling from 8.1 to 16.0 mL/s. The range of Qmax improvement was between 35.2% and 203%. Given the success of pharmacologic approaches to BPH and emerging Table 1 Baseline Characteristics of Patients Enrolled in a Study of ILC Versus -Blockade Tamsulosin (n 19) ILC (n 21) Age (y) 60.7 7.40 63.4 10.06 AUA total score 24.4 6.20 23.2 4.71 Characteristic AUA QoL score 4.4 0.77 4.4 0.59 Qmax (mL/s) 9.5 2.83 9.5 2.57 208.3 74.84 268.9 129.13 PVR volume (mL) 45.6 42.93 73.6 69.59 TRUS volume (mL) 43.7 10.88 37.0 15.45 Voided volume (mL) Values are mean standard deviation. All differences between treatment groups were not significant at the .05 level. AUA, American Urological Association; ILC, interstitial laser coagulation; QoL, quality of life; Qmax, peak urinary flow rate; PVR, postvoid residual; TRUS, transrectal ultrasound. REVIEWS IN UROLOGY ILC Versus -Blockade for BPH endpoints included Qmax, postvoid residual volume, patient global impressions, clinician global impressions, clinician global assessment, O’Leary sexual function questionnaire score, AUA quality-of-life score, and SF-12 health survey results. Safety parameters were studied, including all adverse events. Entry criteria were age greater than 50 years, symptomatic BPH, entry AUA symptom score of 12 to 32, and Qmax of 3 to 15 mL/s. Men with postvoid residual volumes of more than 300 mL were excluded. Patients previously treated with -blockers were allowed to be enrolled after a 4week washout before randomization. If patients were taking a 5-reductase inhibitor, they needed to discontinue for a minimum of 3 months before the first visit. Men with a prostatespecific antigen (PSA) level greater than 4.0 ng/mL but less than 10.0 ng/mL were required to have had a negative biopsy result within 6 months. Patients with a PSA level greater than 10.0 ng/mL were not enrolled. Prostate volume needed to be less than 70 mL, as evidenced by transrectal ultrasound. Subjects randomized to the surgical arm underwent the surgical procedure at the time of randomization and Table 2 Summary of AUA Symptom Scores AUA Score Tamsulosin (n 19) ILC (n 21) P (Tamsulosin vs ILC) Total score Baseline 6 mo Change from baseline Within-treatment P 24.4 6.20 19.2 7.52 5.2 6.32 .002 23.2 4.71 11.4 5.78 11.1 6.69 .001 .524 .001 .030 Quality-of-life score Baseline 6 mo Change from baseline Within-treatment P 4.4 0.77 3.4 1.22 1.0 1.05 .001 4.4 0.59 2.2 1.20 2.2 1.25 .001 .885 .007 .002 Irritative subscore Baseline 6 mo Change from baseline Within-treatment P 11.7 2.17 9.5 2.55 2.2 2.35 .001 9.6 3.41 5.4 3.33 3.8 3.80 .001 .025 .001 .004 Obstructive subscore Baseline 6 mo Change from baseline Within-treatment P 12.7 5.28 9.8 5.86 2.9 4.71 .015 13.7 2.76 6.0 3.62 7.3 3.85 .001 .474 .025 .005 Values are mean ± standard deviation. AUA, American Urological Association. ILC Versus -Blockade Ethicon Endo-Surgery has initiated a randomized trial comparing -blockade with ILC. Results from the study will be an important addition to our understanding of the optimal treatment approaches to BPH. Preliminary results are reported here. The objective of this study was to compare the efficacy and safety of ILC with -blockade using tamsulosin. The primary study endpoint was AUA symptom score. Secondary Figure 1. Mean American Urological Association (AUA) total symptom score by visit. ILC, interstitial laser coagulation. 30 Mean AUA Symptom Score minimally invasive technology, clinicians and patients alike would benefit from comparative studies. Unfortunately, few exist in the literature. Djavan and colleagues3 randomized men to receive an -blocker or TUMT; terazosin was used as the -blocker. The study demonstrated that the initial improvement in symptoms was greater in patients treated with the -blocker; however, long-term outcomes were superior in men treated with TUMT. 25 20 24.4 23.2 19.2 17.5 17.1 15 10 12.7 12.2 11.4 5 0 Baseline Week 4 3 months 6 months Visit Tamsulosin ILC VOL. 7 SUPPL. 9 2005 REVIEWS IN UROLOGY S31 ILC Versus -Blockade for BPH continued Table 3 Uroflowmetry Results and Postvoid Residual Volumes Tamsulosin (n 19) ILC (n 21) Qmax (mL/s) Baseline 6 mo Change from baseline 9.5 2.83 10.9 5.24 1.3 3.54 9.5 2.77 10.9 5.88 1.0 5.80 Voided volume (mL) Baseline 6 mo Change from baseline 208.3 74.83 188.0 70.25 9.9 117.28 268.9 129.13 214.4 109.07 77.1 207.22 45.6 42.93 45.0 44.62 7.9 26.23 73.6 69.59 51.7 77.98 27.6 73.26 Postvoid residual volume (mL) Baseline 6 mo Change from baseline Values are mean standard deviation. All within- and between-group comparisons were not significant at the .05 level. were required to complete telephone follow-up visits at 2 to 7 days, followed by study visits at 4 weeks, 12 weeks, 24 weeks, 52 weeks, 18 months, and 24 months. The subjects randomized to tamsulosin treatment commenced treatment at the time of randomization and had the same follow-up schedule. Treatment with ILC was protocol specified and included 2 treatments per lobe (4 treatments total) for men with a prostate volume of less than 35 mL, 6 treatments for men with a gland volume of 35 to 50 mL, and 8 treatments for those with a gland volume of 50 to 70 mL. The ILC technique was similar to the method reported previously.1 With a planned enrollment of 90 subjects in each arm and a 15% dropout rate, this study was powered at the Percentage of subjects Figure 2. Patient global improvement assessment. ILC, interstitial laser coagulation. 100 5 6 7 80 60 57 79 40 65 20 0 18 29 82 36 16 Tamsulosin week 4 Tamsulosin 6 months ILC week 4 ILC 6 months Visit Significantly improved S32 VOL. 7 SUPPL. 9 2005 Minimally improved REVIEWS IN UROLOGY Worse 80% level to detect a 3-point drop from mean baseline AUA symptom score at the 6-month follow-up visit. Preliminary analysis of the trial included 10 centers, with 40 subjects treated. Twenty-five men have reached 6 months of follow-up.4 Table 1 shows the baseline characteristics in the 2 groups. As is apparent, there is no significant difference between the cohorts, indicating that randomization was uniform. Figure 1 demonstrates the AUA total score by visits over the 6-month study. There was a significant improvement in symptom score in those men randomized to ILC compared with those receiving the blocker. There was a greater than twofold decrease in the average AUA symptom score at 6 months in the 2 cohorts, favoring ILC (11.1 vs 5.2; P .030) (Table 2). The AUA quality-of-life instrument results are also shown in Table 2. At 6 months there was a statistically significant improvement in quality of life for those men undergoing ILC but no difference for those men treated with the -blocker. Both treatment arms experienced statistically significant improvements in irritative and obstructive symptom subscore (Table 2); however, the improvement was greater in men treated with ILC. Uroflowmetry results and postvoid residual volumes are shown in Table 3. There was no significant improvement either within or between treatment groups at the .05 level. Individual patient assessment of outcomes is shown in Figure 2. Assessment by 9 of 11 ILC patients indicated global improvement of at least “significantly improved,” at 6 months compared with 5 of 14 patients receiving tamsulosin. Owing to patient dissatisfaction, 3 of the men receiving tamsulosin underwent ILC at 6 months. Adverse events are depicted in Table 4. Note the relatively low rate of any adverse reactions in both groups. ILC Versus -Blockade for BPH Table 4 Adverse Events Tamsulosin (n = 19) Event ILC (n = 21) n (%) Event n (%) Appendicitis 1 (5) Anxiety 1 (5) Backache 1 (5) Diarrhea 1 (5) Coughing 1 (5) Dysuria 1 (5) Dizziness 1 (5) Edema 1 (5) Ejaculation disorder 1 (5) Hematuria 1 (5) Ejaculation failure 1 (5) Hypertension 1 (5) Hair disorder not otherwise specified 1 (5) Lesion, lung 1 (5) Headache 1 (5) Nocturia 1 (5) Inflammatory swelling 1 (5) Tachycardia 1 (5) Indigestion 1 (5) Throat sore 1 (5) Hematuria 1 (5) Thrush 1 (5) Micturition burning 1 (5) Urge incontinence 1 (5) Mouth dry 1 (5) Urinary frequency 1 (5) Nasal congestion 1 (5) Urinary retention 1 (5) Worsening BPH 1 (5) 4 (21) Subjects with at least 1 adverse event 2 (10) Subjects with at least 1 adverse event BPH, benign prostatic hyperplasia. These data demonstrate that treatment with the Indigo Optima laser is associated with a statistically significant decrease in AUA symptom score to a degree that is superior to that achieved with an -blocker. The onset of symptomatic improvement is not as rapid as with pharmacologic approaches. However, the 6-month data seem to indicate that patients do better with this minimally invasive thermotherapy. Obviously, we must await the completion of the trial before definitive conclusions can be drawn. References 1. 2. 3. 4. Kursh ED, Concepcion R, Chan S, et al. Interstitial laser coagulation versus transurethral prostate resection for treating benign prostatic obstruction: a randomized trial with 2-year follow-up. Urology. 2003;61:573-578. Muschter R. Interstitial laser therapy of benign prostatic hyperplasia. In: Graham SD Jr, Glenn JF, eds. Glenn’s Urological Surgery, 5th ed. Philadelphia: Lippincott-Raven;1998:1111-1117. Djavan B, Seitz C, Roehrborn CG, et al. Targeted transurethral microwave thermotherapy versus alpha-blockade in benign prostatic hyperplasia: outcomes at 18 months. Urology. 2001;57:66-70. Roehrborn CG, Rhee EY, Miller SD, et al. Initial results of a randomized multi-center trial comparing the efficacy and safety of Indigo Optima laser treatment with tamsulosin in men with LUTS and BPH [abstract 1565]. J Urol. 2005; 173(4 suppl):424. Main Points • Despite the success of pharmacologic approaches, there has been a significant effort to develop minimally invasive surgical approaches to the treatment of benign prostatic hyperplasia. • Interstitial laser coagulation (ILC) is a minimally invasive procedure that can be performed under local, regional, or general anesthesia. • In ILC, the laser fiber is introduced into the prostatic tissue transurethrally, and laser energy is introduced to raise the temperature of prostatic tissue. • This is an operator-dependent procedure, and the surgeon can selectively control placement of the laser fiber to achieve the optimum destruction of tissue. • With ILC, there is minimal injury to the urothelium, thus irritative symptoms are minimized; coagulative necrosis results in a significant decrease in prostate volume, which occurs over several months. • Preliminary (6-month) data from a randomized trial demonstrate that treatment with ILC is associated with a clinically significant decrease in American Urological Association symptom scores, superior to that achieved with an -blocker. 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