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PubMed2000

Is transurethral microwave thermotherapy an alternative to medical therapy for patients with benign prostatic hyperplasia?

Scientific evidence supports the safety and efficacy of transurethral microwave thermotherapy (TUMT) as well as medical therapy for management of patients with benign prostatic hyperplasia (BPH). TUMT is being increasingly considered as an alternative to medical management with alpha-blockers or finasteride in patients with lower urinary tract symptoms of BPH. Enduring clinical benefits have been demonstrated after a single 1-hour microwave treatment session under topical anesthesia, and associated morbidity is low. Optimal results are obtained with the delivery of high thermal doses and accurate targeting of microwave energy. Extensive evidence from randomized clinical trials supports the safety and efficacy of both microwave treatment and medical management. Randomized clinical trial data have only recently become available directly comparing these two approaches to BPH treatment. These data indicate that greater long-term improvements in symptoms, peak urinary flow rates, and quality of life are attained with microwave treatment as compared with alpha-blockade. Furthermore, the actuarial rate of treatment failure is markedly lower in patients undergoing microwave vs. alpha-blocker treatment. However, the onset of action with alpha-blocker treatment is more rapid. Limitations of alpha-blockade are side effects and lack of efficacy leading to treatment failure in some patients. Maximal effects of finasteride are modest and require a period of months to be manifested, although the side effect profile and tolerability of this agent are favorable. Neoadjuvant and adjuvant alpha-blocker therapy can accelerate symptom and flow rate improvement after microwave treatment. In contrast to medical management, microwave treatment is highly versatile, allowing patients over a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success. Compared with medical management, microwave treatment also appears to possess greater versatility, allowing patients who fall within a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2000

Relationship between gene expression of nitric oxide synthase and androgens in rat corpus cavernosum.

OBJECTIVE: To clarify the dependence of neural nitric oxide synthase mRNA (nNOSmRNA) and endothelial nitric oxide synthase mRNA (eNOSmRNA) on androgens (testosterone [T] and dihydrotestosterone [DHT]). METHODS: 160 male Sprague Dawley (SD) rats were divided into Groups A (56 rats, 5 weeks old), B (50 rats, 10 weeks old) and C (54 rats, 58 weeks old). Groups A, B and C were all subdivided respectively into five Subgroups. Subgroup 1: intact controls; Subgroup 2: castrated; Subgroup 3: castrated with testosterone undecanoate 25 mg/kg.mon-1, intramuscular injection, Subgroup 4: castrated with testosterone undecanoate 50 mg/kg.mon-1, intramuscular injection and Subgroup 5: treated with finasteride 4.5 mg/kg.day-1, orally. Four and ten weeks after treatments described above, one half of the rats were killed. Serum samples were taken for measurements of T, free testosterone (FT) and DHT by radioimmunoassay. Penile samples were treated with liquid nitrogen and then stored at -80 degrees C. nNOSmRNA and eNOSmRNA were detected by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) and Dot blot. RESULTS: There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 in all Groups A, B and C. The expression of penile eNOSmRNA of Group A was significantly increased (4 weeks model) (P < 0.05) or increased (10 weeks model) (P > 0.05) in Subgroup 2 or 5 compared with those in Subgroup 1. There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 of Group B in 4 weeks model (P > 0.05). There was an elevation when animals were castrated or treated with finasteride in the 10 weeks model. The expression of penile eNOSmRNA of Group C was significantly increased (10 weeks model) (P < 0.05) or increased (4 weeks model) in Subgroup 2 compared with those in Subgroup 1. The production of eNOSmRNA in Subgroup 5 was also increased (including 4- and 10-week models). When T was supplied for castration, the penile eNOSmRNA was decreased to some extent; the greater the dose of T given, the lower penile eNOSmRNA was observed. CONCLUSIONS: The expression of eNOSmRNA in SD rat penile tissue increases while T or DHT diminishes. Sometimes androgens modulate penile eNOSmRNA in opposite directions. There is no correlation between the expression of nNOSmRNA and androgens (including T and DHT). Androgens give rise to penile erection probably not via the NOS pathway.

Androgens↗
PubMed2002

[Experimental study on effect of xiaolong tongbi on nitric oxide synthase and epithelial cell apoptosis in prostate of rats].

OBJECTIVE: To explore the effect of Xiaolong Tongbi (XLTB), a Chinese herbal preparation, on nitric oxide synthase (NOS) containing nerve and epithelial cell apoptosis. METHODS: NOS containing nerve level of various groups prostate was determined by NADPH histochemical staining and morphological quantitative analysis, and the cell apoptosis rate in rats prostatic epithelium was tested immunohistochemically with TUNEL method. RESULTS: After 3 weeks treatment with high dose XLTB, the length density of NOS contained nerves in prostate tissue of rats was 0.113 +/- 0.023, which was significantly different to that in the other 3 groups (low dose XLTB, Finasteride and testosterone) respectively (P < 0.01). Cell apoptosis reached its peak at the day 7 of experiment in XLTB treated groups (9.27%), and Finasteride treated group (5.65%), which lowered slightly at day 14 and got some recovery at day 21. Castration induced cell apoptosis began at day 7 and reached its peak at day 14, which was significantly different from that in the other groups. CONCLUSION: XLTB could increase the NOS contained nerve level and accelerate the apoptosis of epithelial cell in prostate tissue of simulating benign prostatic hyperplasia rats.

Animals↗
PubMed2005

Dutasteride: a review of current data on a novel dual inhibitor of 5alpha reductase.

Dutasteride is used in the treatment of benign prostatic hyperplasia. Like finasteride, it reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% in 2 years. It differs from finasteride in that it inhibits both isoenzymes of 5alpha reductase and results in near-complete suppression of serum dihydrotestosterone. Randomized placebo-controlled trials over 2 years have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate, and reduction of acute urinary retention events and need for surgery. Side effects occurring in therapy with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia. However, when dutasteride treatment is compared with placebo, these sexual adverse events are only modestly elevated. Long-term use over 4 years did not increase side effects. An efficient treatment of side effects is the combination of dutasteride and tamsulosin, especially for patients with large prostate volumes. Finally, the anticancer properties of dutasteride have been shown in placebo-controlled trials and are being investigated in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Duplicate Publication↗
PubMed2003

5-alpha-Reductase Inhibitors Prevent the Progression of Benign Prostatic Hyperplasia.

Lower urinary tract symptoms (LUTS) associated with clinical benign prostatic hyperplasia (BPH) are a common occurrence in aging men, causing bother and interference with daily activities and affecting disease-specific quality of life. There is increasing evidence to suggest that, in many patients, the signs and symptoms of BPH are progressive. Progression can be measured as continued growth of the prostate gland; worsening of symptoms, bother, or quality of life; deterioration of urinary flow rate; episodes of acute urinary retention (AUR); and need for prostate-related surgery. Furthermore, it has become clear that the risk of disease progression increases with age as well as with increasing prostate volume and serum prostate-specific antigen (PSA) level. The 5-alpha-reductase inhibitor finasteride has been shown not only to improve symptoms, bother, and quality of life but also to prevent progression to AUR and surgery, with a relative risk reduction of over 50%. As the risk for such progression is higher in patients with larger glands or higher serum PSA values at baseline, it is in those patients that finasteride induces an even greater risk reduction, making it a cost-effective treatment choice for patients with LUTS associated with prostatic enlargement.

Journal Article↗
PubMed2003

5-alpha-Reductase Inhibitors Prevent the Progression of Benign Prostatic Hyperplasia.

Lower urinary tract symptoms (LUTS) associated with clinical benign prostatic hyperplasia (BPH) are a common occurrence in aging men, causing bother and interference with daily activities and affecting disease-specific quality of life. There is increasing evidence to suggest that, in many patients, the signs and symptoms of BPH are progressive. Progression can be measured as continued growth of the prostate gland; worsening of symptoms, bother, or quality of life; deterioration of urinary flow rate; episodes of acute urinary retention (AUR); and need for prostate-related surgery. Furthermore, it has become clear that the risk of disease progression increases with age as well as with increasing prostate volume and serum prostate-specific antigen (PSA) level. The 5-alpha-reductase inhibitor finasteride has been shown not only to improve symptoms, bother, and quality of life but also to prevent progression to AUR and surgery, with a relative risk reduction of over 50%. As the risk for such progression is higher in patients with larger glands or higher serum PSA values at baseline, it is in those patients that finasteride induces an even greater risk reduction, making it a cost-effective treatment choice for patients with LUTS associated with prostatic enlargement.

Journal Article↗
PubMed2005

A Comparison of Varying alpha-Blockers and Other Pharmacotherapy Options for Lower Urinary Tract Symptoms.

alpha(1)-Adrenoceptor antagonists are now well established as the most common treatment for lower urinary tract symptoms (LUTS) suggestive of bladder outflow obstruction associated with benign prostatic hyperplasia. Both alpha(1)-adrenoceptor antagonists and 5alpha-reductase inhibitors are accepted treatments for LUTS, but with finasteride this applies only to patients with clinically enlarged prostates, whereas alpha(1)-adrenoceptor antagonists are considered to be appropriate treatment for all patients, irrespective of prostate size. Systematic analyses of placebo-controlled studies show that commonly used alpha(1)-blockers are significantly superior to placebo in improving urinary flow and reducing symptoms. Efficacy of alpha-blockers appears to be well maintained over time, and there is no evidence of tolerance or tachyphylaxis to alpha(1)-blockade after 6-12 months' usage. Direct comparative trials show that, in the short term, alpha(1)-adrenoceptor antagonists are more effective than finasteride in reducing symptom score. For alpha(1)-adrenoceptor antagonists, the most commonly reported adverse effects are dizziness, asthenia, postural hypotension, and syncope. Alfuzosin has a more pronounced effect on blood pressure than does tamsulosin, especially in elderly patients. Tamsulosin is well tolerated and has minimal effects on blood pressure; tamsulosin 0.4 mg has the lowest potential to reduce blood pressure and causes less symptomatic orthostatic hypotension than terazosin.

Journal Article↗
PubMed2002

Reducing the risk of benign prostatic hyperplasia progression.

The incidence of benign prostatic hyperplasia increases with age; the probability of progression rises with age at diagnosis and with baseline symptom severity. Although it is not life-threatening, the condition and its complications have a serious impact on quality of life. Acute urinary retention (AUR), though no longer thought an indication for immediate surgery, still requires treatment, often including surgery. Drug therapy with alpha-adrenergic receptor blockers or 5-alpha-reductase inhibitors, such as finasteride, reduces the risk for AUR and the need for surgery, as well as symptoms and bother. Finasteride therapy also results in long-term reduction in prostate volume.

Journal Article↗
PubMed1995

[Hormonal therapy of benign prostatic hyperplasia].

In the last 30 years transurethral prostatectomy (TURP) has been the standard treatment for benign prostatic hyperplasia. While the mortality rate of TURP has been reduced to zero, the postoperative morbidity rate has remained unchanged at 15-18% for several decades. Increasing costs and the preference of many patients for non-surgical treatment have now led to the development of new pharmacological treatment options. All hormone therapeutic modalities known to date, such as GnRH-agonists, cyproteronacetate and flutamide, have acted on the male hypothalamic-pituitary-gonadal system. Because of their side effects they are rarely used for the treatment of symptomatic benign prostatic hyperplasia. The 5-alpha-reductase inhibitor finasteride is a new endocrinological treatment option. It can be used to reduce the volume of enlarged prostates and to improve flow rates without severe side effects. According to the available data, finasteride is a safe treatment option for symptomatic patients with benign prostatic hyperplasia if surgery is not yet indicated. It should not, however, be regarded as an alternative to surgical treatment of benign prostatic hyperplasia.

5-alpha Reductase Inhibitors↗
PubMed1996

[Clinical significance of testosterone and dihydrotestosterone metabolism in women].

Hyperandrogenism in women refers to both excess androgen production and clinical manifestations of androgen excess. Clinical evaluation of women with hyperandrogenism is complex. The synthesis and release of androgenic steroid in women are normal part of adrenal and ovarian steroidogenesis. One of the classic questions concerning androgenic disorders concerns the source of circulating androgens. Relative roles of adrenal and ovary vary greatly, both can be involved. The use of gonadal or adrenal steroid administration can sometimes be used to distinguish the source of androgen excess. In many cases of hyperandrogenism no laboratory diagnosis of adrenal and ovarian androgen overproduction can be made. These patients may have increased androgen sensitivity due to increased enzyme 5 alpha-reductase activity in the skin. To be active in the skin, testosterone (T) must be converted to dihydrotestosterone (DHT) by the 5 alpha-reductase. The increase in DHT production is a localized phenomenon and there is no generalized increase in enzyme activity in women with hyperandrogenism. DHT is rapidly converted to other steroid metabolites including androsteron, androstanediol and their glucuronide and sulfate conjugates. Although once thought to be specific for skin conversion of T to DTH these androgen conjugates reflect adrenal steroid production and metabolism. Antiandrogens (androgen receptor blockers) are the most effective therapeutic modalities of cutaneous hyperandrogenism. Clinical trials are in progress to determine efficacy of finasteride for the treatment of hirsutism and androgenetic alopecia. Finasteride is the first available medication of a new class of drugs that is an competitive inhibitor of 5 alpha-reductase and therefore should be beneficial for medical treatment of cutaneous hyperandrogenism.

Androgen Antagonists↗
PubMedDate not supplied

Comparison of the response of rat testis and accessory sex organs to treatment with testosterone and the synthetic androgen methyltrienolone (R1881).

We have studied the ability of the synthetic androgen methyltrienolone (R1881) to maintain testis and accessory organ weights, as compared to the effect of testosterone propionate (TP). In contrast to TP, R1881 is not metabolized and does not significantly bind to androgen-binding protein (ABP). Thirty-six rats were treated with ethane dimethane sulphonate (EDS) and GnRH antagonist (Org30267) to abolish all testicular androgen production, and recombinant human FSH (rec-hFSH, Org32489) was administered to ensure adequate FSH levels. Of these rats, five groups of four rats were treated daily with 0-, 50-, 100-, 200-, and 400-microgram TP, s.c., and four groups of four rats were treated daily with 150-, 300-, 600-, and 1200-microgram R1881, s.c. One control group of four rats received vehicle injections only. EDS treatment, followed by GnRH antagonist and rec-hFSH treatment for 17 days, significantly reduced testis, prostate, and seminal vesicle weights (P < 0.001, P < 0.01, P < 0.001, respectively). Simultaneous treatment with androgens prevented this organ weight decrease, in a dose-dependent manner. In all TP-treated animals, relative weights (% of control) of the acces, sory sex organs were significantly higher than the relative testis weights (P < 0.001). However, there was no difference in relative weights between testis and accessory sex organs in the R1881-treated animals. In another series of experiments, we investigated the effect of treatment with Finasteride, a 5 alpha-reductase inhibitor, on testis and accessory sex organ weights in rats treated with EDS and TP. Treatment with EDS, TP (300 micrograms/day) and Finasteride (40 mg/kg/day) did not alter testis weight as compared to the effect of treatment with EDS and TP alone. Prostate and seminal vesicle weights were, however, markedly reduced (significantly different from rats treated with EDS and TP alone; P < 0.01 and P < 0.05, respectively). Immunohistochemical analysis of androgen-receptor (AR) expression in the testis revealed that testicular AR immunoexpression is androgen dependent and that FSH alone is not able to maintain AR immunoexpression. Furthermore, the stage-dependent pattern of AR immunoexpression in Sertoli-cell nuclei, during the spermatogenic cycle, is identical in all TP- and R1881-treated rats. It is concluded that testes, prostate, and seminal vesicles are equally stimulated when the androgen receptor in these tissues is exposed to the same intracellular concentration of free androgen and that the low 5 alpha-reductase activity in the testis plays a critical role in the differential response of the testis and the accessory sex organs to T. Furthermore, stage-dependent AR immunoexpression in Sertoli cells does occur in the absence of testicular androgen production and is not due to androgen metabolism or local differences in androgen concentration.

Animals↗
PubMed1997

Intra- and interobserver variability of MRI prostate volume measurements.

BACKGROUND: The Early Intervention Study, a placebo-controlled clinical trial, enrolled approximately 200 patients between age 45-65 years who had mild symptoms associated with early benign hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging (MRI) and read by the local radiologist, who was blinded to the treatment group but not to the sequence of MRI scans. In order to ascertain whether knowledge of the sequence of the MRI scans by the local radiologist was introducing bias in prostate volume changes, a single radiologist was selected to reread all MRI scans at the end of the study. METHODS: Each film was masked as to patient identity, study drug, and date. A new randomization schedule was prepared to blind the single reader to both sequence and treatment. The two sets of readings were compared. RESULTS: Accuracy was dramatically improved when defined as percentage of patients with a 20% or more decrease in prostate volume, from 14% to 0% in placebo patients, and from 38% to 29% in finasteride patients. The variability was significantly reduced (by 50%) when read by a single observer [1]. CONCLUSIONS: A single reader, blinded to time sequence as well as to therapy, improves the accuracy and precision of the measurements when compared to multiple readers, blinded only to drug therapy.

Aged↗
PubMed1997

FR146687, a novel steroid 5 alpha-reductase inhibitor: in vitro and in vivo effects on prostates.

BACKGROUND: Steroid 5 alpha-reductase is implicated in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the in vitro and in vivo effects of FR146687, a new inhibitor of 5 alpha-reductase. METHODS: Two isozymes of rat and human 5 alpha-reductases were expressed in 293 cells. In vivo effects of drugs were evaluated on rat and dog prostates. Castrated immature rats were injected with testosterone propionate (TP) or 5 alpha-dihydrotestosterone propionate (DHTP) to induce growth of the ventral prostates. Testosterone and 5 alpha-dihydrotestosterone (DHT) contents in rat and dog prostates were measured by gas chromatography-mass spectrophotometry (GC-MS). RESULTS: FR146687 showed noncompetitive inhibition in both isozymes and no inhibitory effects on other steroid oxidoreductases. In mature rats and castrated immature rats treated with TP, FR146687 dose-dependently reduced ventral prostate and seminal vesicle weight at doses above 0.1 mg/kg, while castrated immature rats treated with DHTP were not affected by FR146687. FR146687 showed more potent reduction of rat prostates than finasteride. DHT concentration in the prostates was significantly reduced when FR146687 was administered to rats and beagles. CONCLUSIONS: FR146687 is a dual inhibitor for 5 alpha-reductase isozymes and significantly reduced the growth and DHT content in the prostate.

Animals↗
PubMed1998

Identification and partial characterization of two steroid 5 alpha-reductase isozymes in the canine prostate.

BACKGROUND: The dog has been extensively used as an in vivo model to test the pharmacokinetics and effects on pathological prostatic growth of 5 alpha-reductase inhibitors. However, no information is available on the existence or characteristics of canine 5 alpha-reductase isozymes. METHODS: The 5 alpha-reduction of testosterone is analyzed in dog prostatic homogenates. Three human-specific inhibitors are tested for their activity against dog 5 alpha-reductase. RESULTS: Two pH optima of 5 alpha-reductase activity in dog prostatic homogenates are described, comparable to the pH optima of rat and human 5 alpha-reductase isozymes. Kinetic analysis of 5 alpha-reductase enzymatic activity at pH 7.0 revealed isozymes with a low apparent affinity constant (Km = 2.67 nM) and a high apparent affinity constant (Km = 1.23 microM). These apparent affinity constants compare favorably to the human and rat isozymes types II and I, respectively. The human type II inhibitor finasteride selectively inhibited the low Km isozyme, whereas the human type I inhibitor MK386 preferentially inhibited the high Km isozyme. The human type I inhibitor LY306089 was nonspecific for the dog isozymes. CONCLUSIONS: We postulate that the high and low Km isozymes described here represent the dog type I and type II 5 alpha-reductase isozymes, respectively.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMedDate not supplied

The peripubertal male rat assay as an alternative to the Hershberger castrated male rat assay for the detection of anti-androgens, oestrogens and metabolic modulators.

A range of chemicals with various levels of activity as actual or potential endocrine disrupters have been evaluated for activity in the peripubertal male rat assay. The chemicals studied included anti-androgens (vinclozolin), cyproterone acetate, flutamide, 2, 2-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE), metabolic modulators (anastrazole, finasteride, ketoconazole) and oestrogens (butyl benzyl phthalate (BBP), methoxychlor, bisphenol A (BPA), diethylstilboestrol (DES)), the suspected anti-androgen dibutyl phthalate (DBP) and the non-oestrogen fenitrothion. Dosing extended over postnatal days (pnd) 22-35, 36-50, 36-55 and 22-35, with recovery to pnd 55 or 22-55. The endpoints studied were changes in the weights of testes, epididymides, seminal vesicles and prostate. Changes in body weight and the weights of the liver and kidney were also monitored. In some experiments changes in the day of prepuce separation (PPS) were also determined. Only BBP and BPA were inactive in all the assays conducted. Changes in the weight of reproductive tissues provided a sensitive indicator of activity for the remaining chemicals with the exception of DDE, for which higher dose levels could have been used. However, none of the curtailed periods of exposure were able to detect all of the agents. Diethyl stilboestrol, and to a lesser extent DBP and DDE, delayed PPS when exposure occurred over the period pnd 22-55. A complex dependence of the day of PPS on the period of exposure and the body weight of the test animals was observed, and caution is recommended when assessing this endpoint in the presence of reductions in body weight. It is concluded that reproductive tissue weight changes in the peripubertal male have shown sensitivity to a range of biochemical modulators, oestrogens and anti-androgens, and that as such the assay warrants further evaluation. Measurement of delays in PPS may be of value in cases of large delays, but delays of 1-2 days will be difficult to interpret with confidence. The present results are discussed within the context of the sexually mature male rat assay described by O'Connor and the castrated male rat assay described by Hershberger, both of which are the subject of current international study. It is concluded that a decision on the usefulness of the peripubertal male rat assay must await the generation of further data on each of these three assays. There is an urgent need for international agreement on a list of reference endocrine disrupters and their active dose levels, with which to validate individual endocrine disruption assays and batteries of assays.

Anastrozole↗
PubMed1994

The potential for hormonal prevention trials.

Breast and prostate cancer are significant causes of morbidity and mortality and are very similar in etiology, epidemiology, and modalities of treatment. Investigational strategies in the prevention of these malignancies also have strong parallels. The National Cancer Institute is sponsoring several large scale clinical trials involving hormonal manipulation and cancer prevention. In the Breast Cancer Prevention Trial, 16,000 women at high risk for breast cancer are being randomized to receive the antiestrogen agent tamoxifen or placebo for 5 years in an effort to determine if breast cancer development can be inhibited. In a similar trial, the Prostate Cancer Prevention Trial, 18,000 men older than 55 years of age will be randomized to receive finasteride, a 5-alpha-reductase inhibitor, or placebo to determine if inhibition of dihydrotestosterone synthesis in the prostate over a prolonged period will lead to a decreased incidence of prostate cancer. Both clinical trials offer the possibility of demonstrating that a hormonal intervention can decrease an individual's risk of developing breast or prostate cancer. They also have the potential of providing critical information about cancer risk, etiology, screening, and genetics, as well as quantifying the risks and benefits of specific preventive interventions.

5-alpha Reductase Inhibitors↗
PubMed2000

A spectroscopic and crystallographic study of polymorphism in an aza-steroid.

The crystal structures of two enantiotropic polymorphs of the aza-steroid finasteride (N-(1-1-di-methylethyl)-3-oxo-4-aza-5 alpha-and rost-1-ene-17 beta-carboxam ide ) have been determined. The solid-state nuclear magnetic resonance spectra, infrared spectra, and physical property data of these two polymorphs are discussed in relation to both their solid-state structures and hydrogen-bonding networks.

Aza Compounds↗
PubMed2005

Undetectable prostate specific antigen at 6-12 months: a new marker for early success in hormonally treated patients after prostate brachytherapy.

BACKGROUND: The concept of a prostate-specific antigen (PSA) "nadir" has been used as a predictive marker for treatment success in patients treated with radiotherapy for localized prostate carcinoma. However, this approach is not applicable in patients who are concomitantly treated with short-term hormonal therapies. To address this, the authors sought to develop a new predictive marker in such patients after prostate brachytherapy (BT). METHODS: Between March 1997 and November 2002, 194 men with clinical Stage T1A-T3N0M0 prostate carcinoma (according to the 1992 International Union Against Cancer/American Joint Committee on Cancer TNM classification system) were treated with interstitial palladium (103Pd3) BT and androgen ablation therapy with or without external beam radiotherapy (EBRT). Based on tumor characteristics, 127 patients received an antiandrogen, finasteride, and BT whereas 67 received an antiandrogen, leuprolide, and EBRT followed by a BT boost. Hormonal therapy was initiated 2-3 months before any radiotherapy for a total duration of 8-9 months. Follow-up included physical examination and determining the PSA level at 3-month intervals. Postoperative serum testosterone was evaluated in preoperatively potent patients with erectile dysfunction > 6 months after therapy. A PSA level < or = 0.06 ng/mL or < or = 0.20 ng/mL detected during a 6-12-month window after the implant were evaluated as predictors of biochemically disease-free survival (DFS), defined as the time to a PSA level > or = 1.0 ng/mL. RESULTS: Of the 194 patients, 163 were available for analysis. The median length of follow-up was 48 months. In those patients with a PSA level < or = 0.20 ng/mL at 6-12 months, the DFS at 48 months after the implant was 96% (95% confidence interval [95% CI], 91-99%) compared with the remainder of the patients, whose DFS decreased to 80% (95% CI, 65-89%) (P < 0.001). When a PSA level < or = 0.06 ng/mL was used as an indicator, the 48-month DFS was 99% (95% CI, 91-100%) compared with that for patients with a PSA level > 0.06 ng/mL, in whom the DFS was 85% (95% CI, 74-92%) (P = 0.004). Furthermore, because testosterone levels may occasionally remain low after the cessation of luteinizing hormone-releasing hormone agonist therapy and result in erectile dysfunction and an artificially low PSA level, the authors reviewed the serum testosterone levels in 23 patients who were so treated and were experiencing erectile dysfunction. None had PSA values below the lower limit of normal. CONCLUSIONS: A PSA level < or = 0.20 ng/mL or < or = 0.06 ng/mL measured at 6-12 months after BT appears to be a useful predictive marker for detecting early success in patients with prostate carcinoma who are treated with neoadjuvant androgen ablation and BT. These markers may be used to identify those patients who are at an increased risk of biochemical failure and may be useful in stratifying patients for closer follow-up, long-term adjuvant therapies, or clinical trials. A longer follow-up period will be needed to verify whether these are predictive of long-term cancer control.

Adenocarcinoma↗