Perinchery Narayan

A Randomized, Placebo-Controlled Multicenter Study of the Efficacy and Safety of Terazosin in the Treatment of Benign Prostatic Hyperplasia

The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy.

The role of transrectal ultrasound-guided biopsy-based staging, preoperative serum prostate-specific antigen, and biopsy Gleason score in prediction of final pathologic diagnosis in prostate cancer.

OBJECTIVESnTo evaluate the role of ultra sound-guided systematic and lesion-directed biopsies, biopsy gleason score, preoperative serum prostate-specific antigen (PSA) as three objective and reproducible variables to provide a reliable combination in preoperative identification of risk of extraprostatic extension in patients with clinically localized prostate cancer.nnnMETHODSnThe case records of 813 patients who underwent radical prostatectomy for clinically localized prostate cancer were analyzed. All had multiple systematic biopsies, two to three from each lobe, in addition to lesion-directed biopsies. Additionally, biopsies were done on seminal vesicles (SVs), if abnormal. Based on biopsy results, patients were classified as having stage B1 (T2a-T2b) or B2 (T2c) disease, depending on whether biopsies from one or both lobes were positive and stage C (T3) if there was evidence of SV involvement by biopsy of biopsies from areas of extracapsular extension as seen on transrectal ultrasound (TRUS) were positive. Logistic regression analyses with log likelihood chi-square test was used to define the correlation between individual as well as combination of preoperative variables and pathologic stage.nnnRESULTSnOn final pathologic examination, 473 (58%) patients had organ-confined disease, 188 (23%) had extracapsular extension (ECE), with or without positive surgical margins, and 72 (9%) had SV involvement. Eighty (10%) patients had pelvic lymph node metastases. Biopsy-based staging was superior to clinical staging in predicting final pathologic diagnosis. Logistic regression analyses revealed that the combination of biopsy-based stage, preoperative serum PSA, and biopsy Gleason score provided the best prediction of final pathologic stage. Probability plots constructed with these data can provide significant information on risk of extraprostatic extension in individual patients.nnnCONCLUSIONSnThis study demonstrates that TRUS-guided systematic biopsy in combination with preoperative serum PSA and biopsy Gleason score may provide a cost-effective approach for management decisions and prognostication in patients with prostate cancer.

A SECOND PHASE III MULTICENTER PLACEBO CONTROLLED STUDY OF 2 DOSAGES OF MODIFIED RELEASE TAMSULOSIN IN PATIENTS WITH SYMPTOMS OF BENIGN PROSTATIC HYPERPLASIA

PURPOSEnIn a double-blind, phase III clinical trial we evaluate the safety and efficacy of 0.4 and 0.8 mg. tamsulosin daily for the treatment of patients with symptoms of moderate to severe benign prostatic hyperplasia.nnnMATERIALS AND METHODSnPatients meeting the basic requirements of the study underwent a 4-week single-blind placebo evaluation period. A total of 735 patients were randomized to double-blind therapy with tamsulosin or placebo. Treatment duration was 13 weeks. Efficacy and safety were evaluated at 5 visits during the double-blind treatment period.nnnRESULTSnWhen efficacy data between baseline and end point were compared there was a significant reduction in total American Urological Association symptom score (25%) in each tamsulosin group compared with placebo (p = 0.01) and the percentage of patients with a 30% or more reduction in peak urinary flow rate was significantly greater in the tamsulosin versus placebo group (p <0.05). Improvements in American Urological Association symptom scores and maximum flow rate occurred at 1 week of treatment. None of the patients experienced a first dose effect. There were no significant changes in blood pressure on standing at any visit during the study except for a decrease in systolic blood pressure of 20 mm. Hg or more between the 0.8 mg. dose and placebo groups at visit 4 (p = 0.036). Positive orthostatic tests were significantly more frequent in the 0.8 mg. group compared with placebo at visit 4 (p = 0.012). The treatment groups did not differ significantly in incidence of electrocardiogram abnormalities at each post-baseline visit and at end point.nnnCONCLUSIONSnTamsulosin was safe and effective, and clinically and statistically superior to placebo in relieving symptoms of benign prostatic hyperplasia in men with moderate to severe symptoms at baseline. There was no evidence of a first dose effect and no clinically significant orthostatic hypertension. In addition, response to treatment was rapid.

Understaging and undergrading of prostate cancer Argument for postoperative radiation as adjuvant therapy

This report reviews the staging and grading errors that occurred in a consecutive series of 14 patients treated for prostate cancer by radical prostatectomy and of 58 patients treated by both radical prostatectomy and pelvic lymphadenectomy. Almost half of the patients who were in Stages A2, B1, or B2 by clinical criteria were in pathologic Stage C when both capsular perforation and seminal vesicle invasion were used as the criteria for Stage C disease. Seminal vesicle invasion was the more important prognostic factor. Moreover, the pathologic grade of cancer, as determined by needle or transurethral biopsy, was underestimated in 39 per cent of the cases; when the grade was corrected, the patient often was in a worse prognostic group than the one originally assigned. Thus, in this series, more than 40 per cent of the patients were at high risk of persistent or recurrent disease after radical prostatectomy. Radiation was given after operation to 22 such high-risk patients and was well tolerated.

Focal "nerve-sparing" cryosurgery for treatment of primary prostate cancer: a new approach to preserving potency.

OBJECTIVESnTo present a pilot study in which 9 patients treated with focal, unilateral nerve-sparing cryosurgery were followed for up to 6 years. Cryosurgery, in which the whole gland is frozen, has a high rate of impotence, similar to non-nerve-sparing radical prostatectomy.nnnMETHODSnBefore focal nerve-sparing cryosurgery, all patients underwent repeated biopsy on the side opposite the previous positive biopsy. One neurovascular bundle was spared on the side opposite the positive biopsy. Just before the start of freezing, a 22-gauge spinal needle was placed into Denonvilliers fascia using a transperineal route, and saline was injected to separate the rectum from the prostate. Combined hormone therapy was stopped in all patients postoperatively. The prostate-specific antigen (PSA) level was obtained every 3 months for the first 2 years and then every 6 months thereafter. Patients were considered to have a stable PSA if they had two consecutive PSA measurements without a rise. All patients were strongly encouraged to undergo routine biopsies despite a stable PSA level.nnnRESULTSnBetween June 1995 and November 2000, 9 patients underwent focal, nerve-sparing cryosurgery. The follow-up ranged from 6 to 72 months (mean 36). All patients had stable PSA levels at last follow-up. Six patients routinely biopsied had negative biopsies. Potency (defined as an erection sufficient to complete intercourse to the satisfaction of the patient) was maintained in 7 of 9 patients.nnnCONCLUSIONSnFocal nerve-sparing cryosurgery, in which one neurovascular bundle is spared, appears to preserve potency in most patients without compromising cancer control. These preliminary results warrant further study.

Ejaculation and Fertility After Extended Retroperitoneal Lymph Node Dissection for Testicular Cancer

We studied ejaculation and fertility in 55 men who had undergone suprahilar extended retroperitoneal lymphadenectomy for nonseminomatous testicular cancer between 1972 and 1980. Antegrade ejaculation had returned spontaneously in 25 patients, with sperm counts of 35 to 190 million per ml., and normal morphology and motility in 20. The other 5 men either refused to provide semen for analysis or had had vasectomies but all had fathered children postoperatively. Ten men in whom antegrade ejaculation had not returned spontaneously were treated wih sympathomimetic drugs. Antegrade ejaculation was induced in 5 patients, 1 of whom fathered a child while taking the drugs. Two other patients who had only small volumes of ejaculate also responded well to sympathomimetic drugs. A therapeutically sound retroperitoneal node dissection can be performed for testicular cancer without impairing fertility permanently in a significant number of patients.

Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia

OBJECTIVESnTo investigate the long-term efficacy and safety of tamsulosin in patients with benign prostatic hyperplasia and to monitor the increases and decreases in therapeutic response over time. Tamsulosin, a uroselective alpha-adrenergic receptor antagonist for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia, targets alpha(1A)-adrenergic receptors of prostatic smooth muscle with greater affinity than the vascular alpha(1B) receptors. Since the alpha(1A)-adrenoceptor subtype mediates prostatic smooth muscle tension, alpha(1A)-adrenoceptor antagonists may diminish toxicity, with few unwanted effects on blood pressure, while still providing efficacious treatment.nnnMETHODSnThis study extended two 13-week trials and one 40-week extension trial for an additional 64 weeks. On study entry, all patients (n = 949) received 0.4 mg/day tamsulosin. Baseline values were taken from either those of the previous trials for patients who had been treated with tamsulosin or the first visit of this study for patients not previously exposed to the drug. The primary efficacy parameters were the changes in the total American Urological Association (AUA) symptom score, mean peak urinary flow rate (Qmax), and percentage of patients having 25% or greater improvement in the total AUA symptom score and 30% or more improvement in the Qmax. Safety was assessed primarily on the incidence and severity of adverse events and discontinuations due to adverse events.nnnRESULTSnImprovements from baseline were seen in all primary efficacy parameters and were maintained throughout the study. The changes from baseline for the total AUA symptom score and Qmax were statistically significant (P <0.001) at all 3-month intervals. Tamsulosin was well tolerated, and the incidence of adverse events did not increase over time. The mean sitting vital signs did not vary from baseline or relative to the treatment duration.nnnCONCLUSIONSnTamsulosin was safe and effective in long-term treatment (longer than 1 year) of benign prostatic hyperplasia.

Varicocele and Male Subfertility

Unilateral and bilateral subclinical varicocele was found by internal spermatic venography in 10 of 30 men with stress-pattern semen and normal endocrine profiles. Seven of the 10 had no clinical evidence of varicocele. Right-sided varicocele may be almost as common as varicocele on the left and may be responsible for much of the bilateral effect of clinical left-sided varicocele. Transjugular venography has a low morbidity rate and can be used to clarify the relation between subclinical varicocele and infertility. The technique also permits nonsurgical treatment of varicocele.

Comparison of the efficacy and safety of finasteride in older versus younger men with benign prostatic hyperplasia.

OBJECTIVESnTo compare the efficacy and safety of finasteride 5 mg in older (65 years old or older) versus younger (45 to younger than 65 years old) men with benign prostatic hyperplasia (BPH).nnnMETHODSnThe Proscar Long-Term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men 45 to 78 years old with symptomatic BPH, enlarged prostates, and no evidence of prostate cancer. The endpoints included urinary symptoms, prostate volume, occurrence of acute urinary retention and/or BPH-related surgery, and safety.nnnRESULTSnIn both age cohorts, finasteride treatment led to a 51% reduction (P <0.001) in the relative risk for acute urinary retention and/or BPH-related surgery, a significant (P <0.001) and durable improvement in symptom score, and a significant (P <0.001) and sustained reduction in prostate volume. Within each age cohort, no significant differences were found between the placebo and finasteride-treated patients in the incidence of cardiovascular adverse events. Significant differences were evident between the placebo and finasteride groups in the incidence of the typical, known, drug-related adverse events, but no specific differences were associated with age. No drug interactions of clinical importance were observed in the finasteride-treated patients.nnnCONCLUSIONSnThe present analysis from PLESS demonstrates that in both older (65 years old or older) and younger men with symptomatic BPH and enlarged prostates, finasteride is highly effective in improving symptoms and reducing prostate volume in many men and in reducing the risk of acute urinary retention and BPH-related surgery. In addition, the safety profile of finasteride in both older and younger men is similar and no drug interactions of clinical importance were observed.

Transvenous embolization of internal spermatic veins Nonoperative approach to treatment of varicocele

Eleven men, shown on routine spermatic venography to have bilateral varicocele, underwent transjugular bilateral embolization of the internal spermatic veins with stainless steel coils or Ivalon plugs. Embolization of the left spermatic vein was successful in 9; in the other 2 it was not attempted because of aberrant drainage of the vein. Embolization of right spermatic vein was successful in 8 patients. There were three complications, none of which was serious. These preliminary results suggest that both internal spermatic veins can be occluded consistently by the transjugular approach. However, it has not yet been established that fertility is improved by detecting and correcting varicocele on the right side.