Purpose: Many advances have occurred during the last decade in the clinical use of prostate specific antigen (PSA) for detecting, staging and monitoring prostate cancer. We review the clinical usefulness and limitations of serum PSA as a tumor marker of prostate cancer.Materials and Methods: The English language literature was reviewed with respect to the major contributions and limitations of PSA in present clinical practice.Results: Although controversial, age specific PSA reference ranges can improve the sensitivity for prostate cancer detection in young men and the specificity in older men. Percent free PSA improves the specificity for prostate cancer detection in men with PSA values between 4 and 10 ng./ml., and a PSA density of greater than 0.15 may better distinguish benign prostatic hyperplasia from prostate cancer. PSA velocity can improve the ability to detect prostate cancer when 3 serial PSA values are measured during a 2-year period. For prostate cancer staging PSA is most useful combined with clinical stage and Gleason score in multivariate analysis. Percent fr ee PSA may prove useful for staging prostate cancer but further clinical trials are needed to determine its clinical usefulness. PSA is the most clinically useful means to monitor disease recurrence after treatment of prostate cancer. With ultrasensitive PSA assays it is now possible to increase the lead time for detection of disease recurrence by several months.Conclusions: During the last decade much of the focus has been on improving the ability of this tumor marker to detect prostate cancer. PSA remains the best and most widely used tumor marker in urology today.

Objectives. Although digital rectal examination (DRE) for the detection of prostate cancer has been recommended by many professional groups and has become part of the general physical examination, no randomized clinical trial has demonstrated the efficacy or effectiveness of this practice. We conducted a population-based case-control study to evaluate the association between DRE and prostate cancer mortality.Methods. With the resources of the Rochester Epidemiology Project, all 173 men who died of prostate cancer in Olmsted County from 1976 to 1991, who were resident at the time of diagnosis, were identified. For each case, two control patients were drawn from the population, matched for residence at the time of diagnosis in the case, birth date, and duration of medical record in Olmsted County. Trained nurse abstractors reviewed the community medical records for up to 10 years before the date of diagnosis in the case for mention of DRE and specific findings associated with each mention.Results. Case subjects were less likely than control subjects to have had any DRE in the 10 years before diagnosis (matched odds ratio [OR] = 0.51; 95% confidence interval [CI] = 0.31, 0.84). When limited to DREs without mention of signs or symptoms that might raise suspicion of prostate cancer, the association was even stronger (OR = 0.31; 95% CI = 0. 19, 0.49). Adjustment for educational attainment, marital status, and comorbid conditions did little to alter the associations.Conclusions. These results demonstrate a strong inverse association between DRE and prostate cancer mortality. If further research concludes this association to be causal, screening DREs may have prevented as many as 50% to 70% of deaths due to prostate cancer that.might have occurred in the absence of screening. UROLOGY 52 173-179, 1998: (C) 1998, Elsevier Science Inc. All rights reserved.

Artificial neural networks (ANNs) are complex mathematical models that are distantly based on the human neuronal structure. They are capable of modeling elaborate biologic systems without making assumptions based on statistical distributions. Preliminary work has been reported on their application in urology. The initial results have been promising, particularly as an additional tool in the detection of early prostate cancer using the ProstAsure Index, which has been the most extensively studied urologic ANN to date. We review the basic concepts behind ANNs and examine currently existing and potential future applications of this new dynamic technology both in urology and in general clinical medicine.

Prostate cancer (PCa) has become a major concern for men and health organizations worldwide. In the United States, approximately 317,000 new cases and 40,000 deaths from this disease are expected for 1996. 1 Parker S.L Tong T Bolden S Wingo P.A Cancer statistics, 1996. CA Cancer J Clin. 1996; 46: 5-27 Crossref PubMed Scopus (1971) Google Scholar This makes PCa the most frequently detected malignancy in men and the second leading cause of cancer death in the adult male population. In recent years, major efforts have been put forth to reduce the mortality rate from this entity. In short, this means early detection and local definitive therapy, since there is no curative systemic treatment for prostate cancer.

Benign prostatic hyperplasia (BPH) is very common in older men, causing symptoms that can markedly impair quality of life. Surgical treatment, typically transurethral resection of the prostate (TURP), is highly effective but can be costly and is associated with the risk for significant morbidity. Medical treatments for BPH are targeted toward reducing bladder outlet obstruction either by androgen blockade to reduce prostatic volume or alpha-adrenergic blockade to relax the smooth muscle tone of the prostate. In recent years, understanding of the sympathetic innervation of the prostate has improved. This has been paralleled by the development of alpha-adrenergic blocking agents, from nonselective alpha-antagonists, to selective alpha1-antagonists, to the more selective alpha1A-antagonists. It is anticipated that more specific agents will optimize the therapeutic effectiveness of alpha-adrenergic blockade in the prostate while reducing the side effects associated with alpha-adrenergic blockade in other areas of the body, such as the vascular system. This article reviews the evolution of alpha-blockade therapy in management of BPH, focusing on tamsulosin, an agent targeted toward the alpha1A-adrenoceptor that predominates in the prostate. Clinical trials in Europe and the United States have provided evidence that tamsulosin is effective at doses of 0.4 and 0.8 mg/day. At both doses, tamsulosin is associated with significant improvements in the American Urological Association symptom score and the mean and peak urinary flow rates as compared with placebo. This once-daily alpha1A-adrenergic antagonist is well-tolerated, with a minimal potential for the side effects associated with alpha1-blocker therapy.

Objectives. To determine the age- and race-specific prostate-specific antigen (PSA) distributions in healthy men in central South Carolina and to compare these to data from other studies.Methods. Two thousand ninety-two black men aged 40 to 69 years and white men aged 50 to 69 years from the general population in 11 counties of central South Carolina participated in a prostate cancer educational program. Seventy-two percent of the participants were black-about double the proportion in the general population-and 63% of the men (1319 of 2092) subsequently obtained a PSA determination from their own physician. The distribution of serum PSA was compared with distributions from the Olmsted County study and from the Waiter Reed Army Medical Center/Center for Prostate Disease Research study.Results. Older men without cancer had higher PSA levels. Regression analyses yielded an associated increase of about 3.3% per year. Reference ranges for normal PSA in men without cancer (based on their sample 95th percentiles) were zero to 1.9, 3.8, and 5.7 ng/mL in black men aged 40 to 49, 50 to 59, and 60 to 69 years, and zero to 2.7 and 4.9 mg/mL in white men aged 50 to 59 and 60 to 69 years, respectively.Conclusions. Reference ranges for normal serum PSA levels should take into account the population from which they are derived and to which they will be applied. Reference ranges that are useful in the general population can differ from those that are appropriate in a hospital setting. For the general population in central South Carolina, reference ranges for serum PSA levels are lower than previously published reference ranges, particularly among black men. (C) 1998, Elsevier Science inc. All rights reserved.

Percent-free prostate-specific antigen (proportion of free prostate-specific antigen [PSA] to total PSA) has been shown recently in studies on frozen serum samples to be more useful than total PSA alone in distinguishing prostate cancer from benign conditions of the prostate gland. The primary purpose of our study was to determine whether percent-free PSA could predict extraprostatic spread of prostate cancer. We also sought to evaluate the freeze-thaw stability of free PSA. Percent-free PSA values in fresh serum samples were compared with those in aliquots subjected to one to five freeze-thaw cycles. Percent-free PSA values in frozen serum samples from 130 men undergoing radical prostatectomy for clinically localized prostate cancer were compared across pathologic stages. Free PSA levels remained stable for up to five freeze-thaws. Great overlap was found in percent-free PSA values for men with organ-confined disease and those with extraprostatic spread. These results indicate that multiple freeze-thaw cycles do not significantly affect free PSA levels and percent-free PSA is not useful in identifying ideal candidates for radical prostatectomy.

PURPOSE:To describe practice patterns and beliefs of primary care physicians and urologists regarding early detection and treatment of prostate cancer. SUBJECTS AND METHODS:National probability samples of primary care physicians (n=444) and urologists (n=394) completed mail survey instruments in 1995. Physicians were asked about their use of prostate-specific antigen (PSA) testing for men of different ages and their beliefs about the value of radical prostatectomy, external-beam radiation therapy, and watchful waiting for men with differing life expectancies. RESULTS:Most primary care physicians report doing PSA tests during routine examination of men older than 50 years of age. The majority say they continue to do them on patients over 80 years and to refer men with abnormal values for biopsy. In contrast, only a minority of urologists would recommend PSA tests or biopsy for abnormal values for men over 75 years of age. More than 80% of primary care physicians and urologists doubt the value of radical prostatectomy for men with < 10 years of life expectancy; more primary care physicians than urologists see probable survival benefit in radiation therapy for patients with life expectancy < 10 years (48% versus 36%) or > 10 years (67% versus 53%). Thirteen percent of primary care physicians and only 3% of urologists consider watchful waiting to be as appropriate as aggressive therapy for men with > 10 years of life expectancy. CONCLUSIONS:Primary care physicians are more aggressive about PSA testing and referral for biopsy than most urologists recommend. Both groups recommend PSA testing and believe that aggressive treatment is more beneficial than existing evidence indicates.

Objectives, To prospectively analyze whether the treatment of men with clinically benign prostatic hyperplasia (BPH) with alpha blocking agents affects the serum prostate-specific antigen (PSA) levels, and to determine the magnitude of such effect.Methods. Serial PSA measurements were performed using the Abbott IMx assay over 1 year in 134 men over the age of 55 years participating in the Hytrin Community Assessment Trial (HYCAT). HYCAT is a 1-year, randomized, placebo-controlled, double-blinded study of the alpha(1)-adrenergic antagonist terazosin. All men had lower urinary tract symptoms and a clinical diagnosis of BPH with an American Urological Association (AUA) symptom index of 13 points or more, an AUA bother score of 8 points or more, and a peak urinary flow rate of less than 15 mL/s. PSA was measured at baseline and at 8, 26, 39, and 52 (end of study) weeks.Results. Baseline serum PSA levels weakly correlated with patients' age at study entry, and modestly with residual urine (positive correlation) and peak flow rate (negative correlation), although none of the levels were statistically significant. Changes of serum PSA during the course of the study did not correlate with either one of the symptom severity or bother assessment tools, residual urine, or peak flow rate. Mean PSA increased from a baseline of 2.5 +/- 0.22 ng/mL (mean +/- SE) by 0.5 +/- 0.11 ng/mL in the placebo-, and from 2.7 +/- 0.23 ng/mL by 0.3 +/- 0.11 ng/mL in the terazosin-treated patients (P = 0.36 by ANOVA). There were no differences in the changes in serum PSA when patients were stratified by decade of life according to the age-specific PSA reference ranges, or by the final dose of terazosin (2, 5, or 10 mg daily).Conclusions. The treatment of men with lower urinary tract symptoms and clinical BPH with the alpha(1)-adrenergic antagonist terazosin does not affect serum PSA concentration, and thus does not confound longitudinal monitoring of serum PSA levels in patients at risk for prostate carcinoma. (C) 1997, Elsevier Science Inc. All rights reserved.

Objectives. Prostate-specific antigen (PSA) exists in the serum in two clinically important molecular forms: free PSA and PSA complexed to alpha(1)-antichymotrypsin. Total PSA approximates the sum of the free and complexed forms. Preliminary investigations have illustrated the potential benefits of using percent free PSA to enhance the clinical utility of PSA in distinguishing benign prostate disease from prostate cancer. The current study defines the optimal range of total PSA for measuring percent free PSA (reflex range) and generates appropriate cutpoints for percent free PSA within this range.Methods. A total of 413 patients, 225 (54%) with benign prostate disease (mean age, 67 years) and 188 (46%) with prostate cancer (mean age, 66 years), who had PSA values between 2.0 and 20.0 ng/mL participated in the investigation. All patients underwent a sextant biopsy to establish the diagnosis. The serum specimens were assayed with the AxSYM PSA assay (total PSA) and AxSYM Free PSA assay (Abbott Laboratories; Abbott Park, IL). Percent free PSA was calculated for all patients. Receiver operating characteristic (ROC) curves were generated for various ranges of total PSA to determine the reflex range that maximized the increase in sensitivity and specificity of percent free PSA over total PSA. Within the optimal range, the ROC curves were utilized to generate cutpoints for percent free PSA to be used in clinical practice.Results. The appropriate reflex range for the utility of percent free PSA was 3.0 to 10.0 ng/mL. The appropriate cutpoint for percent free PSA when the total PSA value was 3.0 to 4.0 ng/mL to achieve 90% sensitivity for the detection of prostate cancer was 0.19. This approach resulted in a biopsy rate of 73% and a cancer detection rate of 44% in men with a total PSA value between 3.0 and 4.0 ng/mL. The appropriate cutpoint for percent free PSA when the total PSA value was 4.1 to 10.0 ng/mL to ensure 95% sensitivity for detection of prostate cancer was 0.24. Within the range of 4.1 to 10.0 ng/mL, this approach resulted in 13% fewer negative biopsies and failure to detect 5% of the cancers.Conclusions. Percent free PSA should be utilized in patients with a total serum PSA value between 3.0 and 10.0 ng/mL. In patients with a total PSA value between 3.0 and 4.0 ng/mL, percent free PSA enhanced the detection of prostate cancer (improving sensitivity). In patients with a total PSA concentration ranging from 4.1 to 10.0 ng/mL, negative biopsies were eliminated (improving specificity). Copyright 1997 by Elsevier Science Inc.