How do transurethral needle ablation of the prostate and transurethral microwave thermotherapy compare with transurethral prostatectomy?

Throughout the past decade, several minimally invasive therapies for benign prostatic hyperplasia (BPH) have emerged to challenge transurethral prostatectomy (TURP) in efficacy and safety. This review compares high- and lowenergy transurethral microwave thermotherapy (TUMT) and transurethral needle ablation (TUNA) of the prostate with TURP in clinical efficacy and safety. In reducing benign prostatic hyperplasia (BPH) symptoms, TUNA and TUMT are, at best, equal to TURP. However, the effects of TUMT and TUNA on objective measures of obstructive uropathy are minimal and less durable compared with TURP. The sole determinant of when and how to treat a patient with BPH is not solely a therapy’s clinical effectiveness. Other multiple factors must be considered, including safety, adverse effects, sexual function, and cost. The role of TUNA and TUMT lies in offering a cost-effective alternative for achieving substantial improvement in quality of life at an acceptable risk level for treatment-associated complications.     

Characterizing TUNA ablative treatments of the prostate for benign hyperplasia with gadolinium-enhanced magnetic resonance imaging

BACKGROUND AND PURPOSE: Transurethral Needle Ablation of the prostate TUNA has been accepted as an office-based treatment for benign prostatic hyperplasia (BPH) for many years. Clinical outcomes have been reported, but the amount and location of the necrosis produced have yet to be characterized. The necrosis caused by TUNA was evaluated by gadolinium-enhanced magnetic resonance imaging (MRI) of the pelvis. PATIENTS AND METHODS: Twelve patients with BPH/lower urinary-tract symptoms underwent standard TUNA, and MRI scans with gadolinium enhancement were performed before and 1 week after treatment. The images were studied using Analyze software to quantify the amount of necrosis compared with the prostatic volume. Transverse, coronal, and sagittal images were obtained to identify the location of the necrosis. RESULTS: New gadolinium defects were seen in all patients after TUNA. The lesions coalesced into continuous areas of necrosis and correlated with the site of needle placement. The mean volume of necrosis was 6.84 cc and equated to 8.6% of the prostate volume. No lesions were found near the apex, urethra, or rectum; and none extended beyond the prostate capsule. CONCLUSIONS: Gadolinium-enhanced MRI demonstrates new vascular defects representing necrosis caused by TUNA of the prostate. This therapy for BPH produces necrotic lesions that can be placed strategically by the surgeon. The standard protocol produces lesions that coalesce to create larger lesions. This MRI study has characterized, for the first time, the heating pattern and intraprostatic necrosis of a complete TUNA procedure.     

A meta-analysis of trials of transurethral needle ablation for treating symptomatic benign prostatic hyperplasia

OBJECTIVES: To investigate the short- and long-term effectiveness of transurethral needle ablation (TUNA) of the prostate for clinical benign prostatic hyperplasia (BPH), using a meta-analysis of all clinical studies involving TUNA. METHODS: Data were extracted from two randomized trials, two non-randomized observational protocols and 10 single-arm studies conducted on TUNA, according to a determined protocol. The meta-analysis was based on the change in the mean score at the end of study from that at baseline. The estimation of the effects from the meta-analysis used a multilevel model including random effects for the studies. RESULTS: In all studies the patients recruited had severe lower urinary tract symptoms and a mean International Prostate Symptom Score (IPSS) of > 20 before treatment. The effect of TUNA was to halve the mean IPSS at 1 year after treatment and, although there was a slight tendency for the IPSS to increase in all arms from year 1 to year 5, this decrease by half was maintained at 5 years. The maximum urinary flow rate (Q(max)) also increased by approximately 70% from baseline to 1 year and in virtually all studies the mean Q(max) approached or exceeded 15 mL/s. Although there was a tendency for Q(max) to decline slightly over time, the mean Q(max) 5 years after treatment was > 50% over baseline. CONCLUSIONS: This meta-analysis shows that TUNA is an effective and minimally invasive treatment for men with clinical BPH, even when the symptoms are severe. There is a significant improvement in symptoms and flow rate after 1 year which persists for at least 5 years. TUNA therapy would appear to be an alternative to surgery and an attractive option for men who do not wish to undergo long-term medical therapy, are poor candidates for surgery or are concerned about the side-effects of TURP.     

The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function： a systematic review

A systematic review of randomized controlled trials and cohort studies was conducted to evaluate data for the effects of minimally invasive procedures for treatment of symptomatic benign prostatic hyperplasia （BPH） on male sexual function. The studies searched were trials that enrolled men with symptomatic BPH who were treated with laser surgeries, transurethral microwave therapy （TUMT）, transurethral needle ablation of the prostate （TUNA）, transurethral ethanol ablation of the prostate （TEAP） and high-intensity frequency ultrasound （HIFU）, in comparison with traditional transurethral resection of the prostate （TURP） or sham operations. A total of 72 studies were identified, of which 33 met the inclusion criteria. Of the 33 studies, 21 were concerned with laser surgeries, six with TUMT, four with TUNA and two with TEAP containing information regarding male sexual function. No study is available regarding the effect of HIFU for BPH on male sexual function. Our analysis shows that minimally invasive surgeries for BPH have comparable effects to those of TURP on male erectile function. Collectively, less than 15.4% or 15.2% of patients will have either decrease or increase, respectively, of erectile function after laser procedures, TUMT and TUNA. As observed with TURP, a high incidence of ejaculatory dysfunction （EjD） is common after treatment of BPH with holmium, potassium-titanyl-phosphate and thulium laser therapies （〉 33.6%）. TUMT, TUNA and neodymium：yttrium aluminum garnet visual laser ablation or interstitial laser coagulation for BPH has less incidence of EjD, but these procedures are considered less effective for BPH treatment when compared with TURP.     

Randomized clinical trial comparing transurethral needle ablation with transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: results at 18 months

PURPOSE: To compare the efficacy and safety of transurethral needle ablation (TUNA) and transurethral resection of the prostate (TURP) for the treatment of benign prostatic hyperplasia (BPH) during an 18-months follow-up. PATIENTS AND METHODS: A series of 59 patients older than 40 years were included in this study. The entry criteria were prostate size <70 g, maximum urinary flow rate (Q(max)) <15 mL/sec, International Prostate Symptom Score (IPSS) >13, and no suspicion of prostate cancer according to the clinical or laboratory findings. Of the patients, 26 (44%) were treated with TUNA and 33 (56%) with TURP. At 3 and 18 months of follow-up, Q(max), postvoiding residual volume (PVR), IPSS, and the quality of life (QOL) score were compared with the baseline values. The results were also compared in patients undergoing TUNA v TURP. RESULTS: Improvements in Q(max), PVR, IPSS, and QOL score were statistically significant for both groups at 3 and 18 months of follow-up. The increase in the mean Q(max) of the TURP group was higher than that in the TUNA group, whereas no significant differences were found in the two groups regarding improvements in IPSS and QOL score. There were no complications associated with the TUNA procedure, while 16 retrograde ejaculation, 4 erectile impairment, 2 urethral stenosis, and 1 urinary incontinence cases were observed after TURP. CONCLUSIONS: The TUNA procedure is an effective and safe minimally invasive treatment with negligible adverse effect for selected patients with symptomatic BPH compared with TURP. It should be considered as an alternative treatment option for younger patients who want to preserve sexual function.     

Efficacy of transurethral needle ablation of the prostate for the treatment of benign prostatic hyperplasia

BACKGROUND: We evaluated the efficacy and safety of transurethral needle ablation (TUNA) of the prostate for treatment of symptomatic benign prostatic hyperplasia (BPH) as one institute participating in a Japanese clinical trial. METHODS: Thirty-three patients with symptomatic BPH were treated with the TUNA procedure in our institute. The international prostate symptom score (IPSS), quality of life (QOL) score, residual urine volume (RV), prostate volume (PV) and peak urinary flow rates (Qmax) were measured and complications were assessed. RESULTS: We followed and evaluated 30 of the 33 cases. At 12 months there were significant improvements in the IPSS (20.7 to 11.2, P < 0.0001), QOL score (4.9 to 2.1, P < 0.0001), RV (46.6 to 22.6 mL, P < 0.01), PV (37.8 to 30.0 mL3, P < 0.002) and Qmax (8.00 to 11.0 mL/s, P < 0.002). There were no serious complications. CONCLUSION: This trial shows that the TUNA procedure is a safe and efficacious treatment for symptomatic BPH.     

Long-term evaluation of transurethral needle ablation of the prostate (TUNA) for treatment of symptomatic benign prostatic hyperplasia: clinical outcome up to five years from three centers

OBJECTIVE: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the major criticism, as with all alternative treatments for BPH, was the lack of long-term data. We present the clinical outcome of patients treated by TUNA and followed for 5 years. METHODS: 188 consecutive patients with symptomatic BPH treated with TUNA were followed for five years in three different centers. All patients were treated using the TUNA II or TUNA III catheters under local anesthesia only without general or spinal anesthesia. Baseline and 5-year follow-up evaluation included urinary peak flow, International Prostate Symptom Score (IPSS) and post-void residual urine (PVR). The number of patients requiring additional medical or surgical treatment was recorded. Statistics were performed using the t-test. RESULTS: At a mean follow-up of 63 months, mean urinary peak flow rate increased from 8.6 ml/s to 12.1 ml/s (p<0.01, t-test), IPSS and PVR decreased from 20.9 and 179 ml to 8.7 and 122 ml, respectively (both p<0.001, t-test). The percentage of patients who improved by at least 50% their peak uroflow and IPSS was 24% and 78% respectively. Mean prostate volume and PSA levels did not change significantly (53.9 cc vs. 53.8 cc and 3.3 vs. 3.6 ng/ml, respectively at 5 years, both p values > 0.05, t-test). Two patients died of unrelated comorbidities and 10 were lost for follow-up. Medical treatment was given to 12 patients (6.4%), a second TUNA performed in 7 patients (3.7%) and surgery indicated in 22/186 (11.1%). Overall 41/176 patients (188 at start, 2 deaths and 10 lost to follow-up) or 23.3% required additional treatment at 5 years follow-up following the original TUNA procedure. CONCLUSIONS: TUNA is effective and provides good long-term clinical improvement at 5-year follow-up. TUNA treatment stands the test of time at 5-year follow-up with low and acceptable failure rates. More than 75% of the patients do not need additional treatment for BPH on the long run.     

良性前列腺增生微创治疗进展

BPH治疗方法有药物治疗、外科治疗及微创治疗等,其中微创治疗因其损伤小、疗效好、恢复快、患者易于接受等优点,越来越多地被泌尿外科医生接受,如经尿道针刺射频消融术(TUNA)、经尿道微波治疗(TUMT)、选择性绿激光前列腺汽化术(PVP)、经尿道钬激光前列腺剜除术(HOLEP)等,本文对此进展进行了综述。     

A cost comparison of medical management and transurethral needle ablation for treatment of benign prostatic hyperplasia during a 5-year period

PURPOSE: We performed an analysis comparing the cost of medical management with TUNA therapy for a 5-year period. MATERIALS AND METHODS: Published costs for tamsulosin, finasteride, transurethral needle ablation (TUNA, Medtronic, Inc., Minneapolis, Minnesota) and transurethral resection of the prostate were used to construct a cost analysis model comparing medication with TUNA. The model analyzed monotherapy with an alpha-blocker (tamsulosin) and a 5alpha-reductase inhibitor (finasteride), combination therapy using both medications, and a mixed scenario using monotherapy and combination therapy. Published data were used to estimate the rate of surgical intervention in patients initially treated with medications or TUNA. RESULTS: Tamsulosin monotherapy was less expensive than TUNA for 5 years ($3,485 for tamsulosin vs $4,811 for TUNA year 5). Finasteride monotherapy reaches a break-even point with TUNA during year 5 ($4,867 for finasteride vs $4,811 for TUNA). Combination therapy reaches a break-even point with TUNA after approximately 2 years 7 months of treatment ($4,515 for combination therapy vs $4,572 for TUNA) and the mixed scenario breaks even with TUNA at approximately year 4 ($4,696 for medical management vs $4,645 for TUNA). CONCLUSIONS: The TUNA procedure compares favorably to combination medical therapy for the treatment of benign prostatic hyperplasia on a cost basis. alpha-Blocker monotherapy is less costly than TUNA while 5alpha-reductase inhibitor monotherapy is approximately equivalent to TUNA for 5 years. The TUNA procedure is less expensive than combination medical management for 5 years, with a break-even point at approximately 2 years 7 months.     

Transurethral needle ablation for chronic nonbacterial prostatitis

OBJECTIVE: To investigate the efficacy of transurethral needle ablation (TUNA) of the prostate for treating chronic nonbacterial prostatitis unresponsive to conservative therapies. PATIENTS AND METHODS: Forty-two patients (mean age 38.5 years, range 25-52) with nonbacterial prostatitis in whom clinical management was unsuccessful in relieving the symptoms or signs of prostatitis were treated using TUNA. All patients had a high leukocyte count (> 15 per high-power field) in expressed prostatic secretions (EPS) with no bacterial growth in either urine or prostatic secretion cultures. Before TUNA all patients were evaluated using a symptom score, satisfaction score (quality of life) and an examination of prostatic secretions. All patients were reassessed using the same variables 1 and 3 months after TUNA. Of the 42 patients, 10 had their semen analysed before and 3 months after treatment. RESULTS: The mean (sd) symptom and satisfaction scores improved significantly, from 11.02 (2.90) to 5.00 (2.61) and from 4.84 (0.57) to 1.26 (1.18), respectively, 3 months after TUNA (both P < 0.05). Of the 42 patients, 30 (71%) had normal EPS results within 3 months of TUNA. Also, of 37 patients with high leukocyte counts (> 100 per high-power field) before TUNA, 26 (70%) had normal EPS results within 3 months afterward, and 29 (78%) had a satisfaction score of < 3 points. CONCLUSIONS: TUNA may be a possible treatment option for patients with chronic nonbacterial prostatitis that is unresponsive to conservative therapies. A long-term follow-up and randomized studies are needed to confirm the efficacy of the TUNA against intractable chronic prostatitis.     

Two-year results of transurethral resection of the prostate versus four 'less invasive' treatment options

OBJECTIVE: The aim of this study was to compare the efficacy or transurethral resection of the prostate (TURP) versus four less invasive treatment options during a 2-year follow-up. MATERIAL AND METHODS: 95 elderly men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) were assigned prospectively to the following five treatment arms; transurethral resection of the prostate (TURP; n = 28), transurethral electrovaporization (TUVP; n = 17), visual laser ablation of the prostate (VLAP; n = 17), transrectal high intensity focused ultrasound (HIFU; n = 20) and transurethral needle ablation (TUNA); n = 15). Preoperative workup included the International Prostate Symptom Score (IPSS), uroflowmetry, post-void residual volume (PVR), prostate volume determined by transrectal ultrasonography and a multichannel pressure flow study. Postoperative follow-up at 6, 12, 18 and 24 months included assessment of IPSS, PVR and uroflowmetry. RESULTS: At study entry, patients assigned to one of the five treatment arms were comparable with respect to age, peak flow rate (Q(max)), IPSS, prostate size and the degree of bladder outflow obstruction. During study, 1 patient in the TURP group (4%) required a secondary TURP, as compared to 23.5% (n = 4) after TUVP, 26.7% (n = 4) after VLAP, 15% (n = 4) after HIFU and 20% (n = 3) following TUNA. In patients not subjected to a secondary procedure, the IPSS decreased a mean 13. 9 after TURP, as compared to 12.7 after TUVP, 12.9 after VLAP, 7.0 after HIFU, and 9.8 after TUNA. Q(max) increased 11.5 ml/s (mean) after TURP, as compared to 11.1 ml/s after TUVP, 5.6 ml/s after VLAP, 2.5 ml/s after HIFU and 2.3 ml/s after TUNA. CONCLUSION: In up to a quarter of the patients, a secondary TURP is performed within the first 2 years after 'less invasive' procedures. These data underline the need for long-term studies to reliably assess the role of less invasive procedures and to indicate that TURP is still competitive.     

Prostatic expression of human 5α-reductase type 2 during finasteride therapy: a randomized, double-blind, placebo-controlled study

This study was aimed at exploring the effect of finasteride, a non-steroidal competitive inhibitor of the enzyme 5α-reductase, on 5α-reductase type 2 at the mRNA level in human prostate, using an in situ hybridization technique. After randomization, 10 men with benign prostatic hyperplasia (BPH) received oral finasteride (5 mg daily) and five men with BPH received placebo daily. Careful clinical examination was carried out and 2 biopsy samples were taken transrectally before the treatment and after 3, 6, and 12 months of treatment. In situ hybridization was carried out and expression of 5α-reductase type 2 mRNA was measured. The results showed that finasteride treatment had no permanent effect on expression of 5α-reductase type 2 in prostatic epithelium, compared with placebo treatment. Expression varied during treatment, but there was no clear tendency in this expression. The signal was localized in the epithelial cells. We conclude that finasteride treatment had no clear effect on human 5α-reductase type 2 expression in the prostate.     

Systematic review and meta-analysis of Transurethral Needle Ablation in symptomatic Benign Prostatic Hyperplasia

Background

Benign prostatic hyperplasia (BPH) constitutes a major clinical problem. Minimally invasive therapies for the treatment of symptomatic BPH include Transurethral Needle Ablation (TUNA), but it is unclear what impact this technique has on the disease and its role among other currently available therapeutic options. The objective of this study is to ascertain the efficacy and safety of TUNA in the treatment of BPH.

Methods

Systematic review of the literature until January 2005 and meta-analysis of clinical studies assessing TUNA in symptomatic BPH. Studies were critically appraised. Estimates of effect were calculated according to the random-effects model.

Results

35 studies (9 comparative, 26 non-comparative) were included. Although evidence was limited by methodological issues, the analysis of relevant outcomes indicates that while TUNA significantly improves BPH parameters with respect to baseline, it does not reach the same level of efficacy as TURP in respect to all subjective and objective variables. Further, its efficacy declines in the long-term with a rate of secondary-treatment significantly higher than of TURP [OR: 7.44 (2.47, 22.43)]. Conversely, TUNA seems to be a relatively safe technique and shows a lower rate of complications than TURP [OR:0.14 (0.05, 0.14)] with differences being particularly noteworthy in terms of postoperative bleeding and sexual disorders. Likewise, TUNA has fewer anesthetic requirements and generates a shorter hospital stay than TURP [WMD: -1.9 days (-2.75, -1.05)]. Scarce data and lack of replication of comparisons hinder the assessment of TUNA vs. other local therapies. No comparisons with medical treatment were found.

Conclusion

The body of evidence on which TUNA has been introduced into clinical practice is of only moderate-low quality. Available evidence suggest that TUNA is a relatively effective and safe technique that may eventually prove to have a role in selected patients with symptomatic BPH. TUNA significantly improves BPH parameters with respect to baseline values, but it does not reach the same level of efficacy and long-lasting success as TURP. On the other hand, TUNA seems to be superior to TURP in terms of associated morbidity, anesthetic requirements and length of hospital stay. With respect to the role of TUNA vis-à-vis other minimally invasive therapies, the results of this review indicate that there are insufficient data to define this with any degree of accuracy. Overall cost-effectiveness and the role of TUNA versus medical treatment need further evaluation.     

Therapeutic effect of transurethral needle ablation in non-bacterial prostatitis: Chronic pelvic pain syndrome type IIIa

AIM: Non-bacterial prostatitis is difficult to manage with conventional treatment. This study was undertaken to evaluate the therapeutic effect of transurethral needle ablation (TUNA) on men with chronic inflammatory non-bacterial prostatitis. METHODS: Thirty-two patients with non-bacterial prostatitis (type IIIa) were treated with TUNA. The TUNA procedure, which uses radiofrequency energy, heats the prostate tissue to approximately 90-110 degrees C over a 5-min period. Evaluation consisted of a prostatitis symptom severity score chart, the monitoring of the leukocyte count in the expressed prostatic secretion (EPS) and a subjective global assessment. RESULTS: The decrease in the prostate symptom severity score chart at 3 and 6 months compared with the baseline assessment was statistically significant. Analysis of the leukocyte levels in the EPS in 14 patients was available. All 14 patients had a decrease in the EPS leukocyte count 3 months after treatment. However, six of these men (43%) still had EPS leukocyte levels above the normal indices (>10 white blood cells per high-power field). A second session of TUNA on these partial responders resulted in three of the six men obtaining a normal EPS leukocyte count. At 6 months following treatment, complete, partial and poor improvement in terms of subjective global assessment were noted in 60, 35 and 5% of patients, respectively. No major complications, including those of sexual dysfunction or retrograde ejaculation, were noted in this cohort. CONCLUSIONS: Transurethral needle ablation appears to be an easy, safe and effective treatment for men with chronic inflammatory non-bacterial prostatitis.     

Urodynamic Outcome after Transurethral Prostatectomy is Related to Percent Area Density of Prostate Smooth Muscle in Patients with Benign Prostatic Hyperplasia

We investigated the relationship between histological composition of the prostate and urodynamic outcome after transurethral resection of the prostate (TURP) in 27 patients with symptomatic benign prostatic hyperplasia (BPH). The histological analysis was performed using computer-assisted quantitative morphometry. Before and after TURP, group-specific urethral resistance factor (URA) was estimated by pressure-flow study. A significant correlation was found (p = 0.01) between the area density of prostate smooth muscle and the improvement in URA. However, no other histological components correlated with the improvement in URA. These facts suggest that the percent area density of prostate smooth muscle in prostatic adenoma appears to be a useful predictive factor for treatment of BPH.     

Newly Developed Equipment and Methods in the Treatment of BPH: Analysis of Present Status

Benign prostatic hyperplasia (BPH) is the most common disease among the aged male population. A variety of symptoms are mainly caused by obstructive changes at the prostatic urethra. Transurethral resection (TURP) has been the gold standard of treatment, but new equipment and methods such as TUMT, HIFU, TUNA, and laser prostatectomy have been developed and are being tested for clinical application. Our experience with new equipment and methods show that their effectiveness has yet to be conclusively evaluated by objective parameters, while subjective improvements have been seen with less invasive treatments such as TUMT, HIFU and TUNA. Laser prostatectomy confirmed its advantages in hemostasis but comparison of each treatment is difficult because of different pathological changes created by different energy sources shown by MRI. Further studies are required to examine the new equipment and methods and for identification of the treatment of choice for BPH.     

Use of 5α-reductase inhibitors to prevent benign prostatic hyperplasia disease

A histologic change in the prostate, benign prostatic hyperplasia (BPH), is a normal part of aging. However, BPH disease, defined here as a life-altering urinary condition caused by BPH requiring prompt medical intervention, is a serious medical disorder associated with major complications, surgical intervention, and severe lifestyle interference. BPH disease is preventable. The rationale for BPH disease prevention rests on four pillars of evidence: (1) BPH disease generally is a progressive disorder; (2) complications and severe lifestyle interference from BPH disease are common and serious; (3) men at greatest risk of BPH disease can be identified using prostate-specific antigen (PSA) level higher than 1.5 ng/mL as a surrogate marker for an enlarged prostate; and (4) 5α-reductase inhibitors (5ARIs) reduce the primary androgen responsible for prostate growth (dihydrotestosterone), shrink the prostate, and arrest the disease process regardless of symptom status. Thus, we now can identify men with an enlarged prostate at risk for BPH disease who may be candidates for preventive therapy with 5ARIs, regardless of urinary symptoms or bother.     

Endocrine treatment of benign prostatic hypertrophy: current concepts.

To summarize the endocrine approach for the treatment of BPH: much clinical data have accumulated over the past forty years. Until recently, scientists and physicians mainly concentrated on the reduction of androgens as a possible solution. We have come a long way from surgical castration, through the administration of hormones such as estrogen and progesterone, gonadotropin-releasing hormone agonists to the inhibition of an enzymatic reaction reducing testosterone to DHT--the now recognized active intracellular androgen metabolite. Recently, the role of estrogens has been emphasized with the finding that stromal hyperplasia is the main change occurring in BPH. Lately, research has been initiated to examine the clinical effect aromatase inhibitors would have in the treatment of human BPH. Since there is enough evidence that both the epithelial and stromal components of the human prostate undergo hyperplasia in BPH, and individuals vary with respect to their relative epithelial/stromal components, both structures would have to be reduced for therapy to be successful. Therefore, the combination of an antiandrogenic and antiestrogenic effect is theoretically promising. Indeed, prostates of beagles shrunken after treatment with an aromatase inhibitor, further decreased in weight after additional treatment with cyproterone acetate, an antiandrogen. We are now approaching the stage where these "antihormones" are both enzyme inhibitors with actually no side effects that preclude the use of the earlier generation's "antihormonal" hormonal drugs. Furthermore, it has recently been reported that the aromatase inhibitor, 4-hydroxy-androstenedione also inhibits human prostatic 5-alpha reductase, at least in vitro. The in vivo relevance of this finding awaits further classification. Thus, a good hormonal treatment that will be both scientifically sound, and clinically safe and effective, seems feasible in the near future. Two main factors have encouraged our interest and research into methods of inhibiting prostatic growth or reducing its obstructive symptomatology: the enormous cost of prostatic operations for outlet obstruction secondary to BPH, and the natural aging process of the population accompanied by deteriorated health precluding anesthesia and prostatic surgery. Medical treatment of BPH has to result in symptomatic improvement, elimination of residual urine, and improvement of flow to be considered successful. These are usually accomplished by surgery and results at least as good as those obtained by operation should be aimed at, if medical treatment is to replace surgery. Although indications for surgery and outcome of operations are well-defined, this is not the case when alternatives to prostatectomy are chosen.(ABSTRACT TRUNCATED AT 400 WORDS)     

Alpha 1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia.

PURPOSE: Recent evidence indicated that an alpha 1 blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, to determine whether this apoptotic response was mediated by alpha 1 adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another alpha 1 blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth. MATERIALS AND METHODS: Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle alpha-actin immunoreactivity. RESULTS: A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p < 0.05). Furthermore, the marked induction of prostatic stroma apoptosis in response to both alpha 1 adrenoceptor antagonists was paralleled by a significant decrease in the smooth muscle alpha-actin expression. This loss of prostatic smooth muscle cells correlated with morphological stromal regression (as detected by trichrome staining) and BPH symptom improvement. Neither terazosin nor doxazosin therapy resulted in significant changes in prostate cell proliferation. CONCLUSIONS: These findings demonstrate that alpha-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to alpha 1 blockade in the treatment of BPH.