Serum Prostate-specific Antigen Determination Research Articles

Performance of a neural network in detecting prostate cancer in the prostate-specific antigen reflex range of 2.5 to 4.0 ng/mL

Objectives. To explore the potential role of a neural network-derived algorithm in enhancing the specificity of prostate cancer detection compared with the determination of prostate-specific antigen (PSA) and free PSA (fPSA) while maintaining a 90% detection rate. Recent information suggests that the incidence of detectable prostate cancer is similar in men whose PSA values range from 2.5 to 4.0 ng/mL and from 4.0 to 10.0 ng/mL. If the PSA threshold triggering a prostate biopsy is lowered to 2.5 ng/mL, approximately 13% of men older than 50 would be added to the patient biopsy pool. Methods. One hundred fifty-one men were enrolled in a prospective, Institutional Review Board-approved protocol to evaluate the incidence of cancer in a population of men who participated in an early-detection program and whose PSA level was between 2.5 and 4.0 ng/mL. All the men underwent biopsy using an 11-core multisite-directed biopsy scheme, and all biopsy specimens were examined by one pathologist. All men had a second blood specimen drawn before the biopsy for a determination of serum PSA, creatinine kinase, prostatic acid phosphatase, and fPSA. A new neural network algorithm was developed with PSA, creatinine kinase, prostatic acid phosphatase, fPSA, and age as input variables to produce a single-valued prostate cancer detection index (PCD-I). This new algorithm was then prospectively tested in the 151 men. Performance parameters (including sensitivity, specificity, positive and negative predictive values, and biopsies saved) were calculated, and a comparative analysis was performed to evaluate the differences among the new algorithm, percent fPSA, PSA density, and PSA density-transition zone. Results. Cancer was histologically confirmed in 24.5% (37 of 151) of the men. The median age of the men was 62 years (range 43 to 74). At a sensitivity of 92%, the specificity for percent fPSA was 11%. The new algorithm (PCD-I) demonstrated an additional enhancement of specificity to 62% at 92% sensitivity. Clinically, the PCD-I would result in a savings of 49% (74 of 151) of all biopsies or 63.6% (71 of 114) of all unnecessary biopsies. Conclusions. A new generation algorithm, derived from a neural network (PCD-I) incorporating the parameters of age, creatinine kinase, PSA, prostatic acid phosphatase, and fPSA can significantly enhance the specificity and reduce the number of biopsies while maintaining a 92% sensitivity rate.

Evaluation of the effect of spinal cord injury on serum PSA levels

Objectives. Prostatic structure and secretory activity are thought to be influenced by autonomic innervation of the prostate. Prostatic denervation is especially likely in patients with spinal cord injury (SCI) at the level of the cauda equina or the conus medullaris, where the peripheral nerve supply to the prostate may be specifically damaged. This may result in changes in serum prostate-specific antigen (PSA) levels, either directly or indirectly. Therefore, we measured serum PSA levels and also studied the influence of factors such as age, catheterization, duration of SCI, urinary tract infection, and history of cystitis on serum PSA values in men with SCI. Methods. Serum PSA levels were determined in 79 men with SCI (age older than 40 years) using banked sera by the Abbott MEIA PSA assay. Variables such as age, catheterization, duration of SCI, urine culture results, and history of cystitis were obtained from a review of patient records. Comparisons were made with a randomly selected, non-SCI control population of 501 men, 40 to 89 years old, who underwent serum PSA determination at our institution. Statistical comparisons were performed using the Mann-Whitney U test (nonparametric), since the populations were not normally distributed. Multivariate logistic regression analysis was used to assess the correlation between the various factors and the serum PSA levels in men with SCI. Results. No statistically significant differences were found in the median serum PSA values between the SCI group and the non-SCI control population. The age-specific PSA values obtained in the SCI group were also comparable to those reported for the general population at large. Age ( P <0.03) and the presence of a catheter ( P <0.0002) were the only two factors that were correlated with higher serum PSA values in the SCI group by regression analysis. Conclusions. Men with SCI tended to have serum PSA value distributions that were similar to those of the general population. However, those in the SCI group who had indwelling catheters were more likely to have higher PSA values at baseline, as were older men with SCI.

Endocrine status in elderly men with lower urinary tract symptoms: correlation of age, hormonal status, and lower urinary tract function

Objectives. To correlate endocrine parameters in elderly men with lower urinary tract symptoms (LUTS) to patient age and clinical parameters such as prostate volume, prostate-specific antigen (PSA) levels, and uroflowmetry and to compare the clinical and endocrinologic parameters in men with or without hypogonadism. Methods. Men (40 years old or older) with untreated LUTS as defined by an International Prostate Symptom Score (IPSS) of 7 or greater due to benign prostatic hyperplasia were included in this study and underwent the following investigations: IPSS, free uroflow study, postvoid residual volume, transrectal ultrasound for assessment of prostate volume, serum PSA determination, and an endocrine study, including testosterone, human luteinizing hormone, human follicle-stimulating hormone, prolactin, dehydroepiandrostendione-sulphate (DHEA-S), and prolactin. Results. Three hundred twelve men (mean age 62.8 ± 10.6 years, range 40 to 91) were analyzed. The serum levels of estradiol (correlation coefficient [ r] = 0.19), human luteinizing hormone ( r = 0.32), human follicle-stimulating hormone ( r = 0.19), and DHEA-S ( r = −0.39) correlated ( P <0.05) with age; no such correlation was seen for testosterone ( r = 0.04; P >0.05) or prolactin ( r = 0.09; P >0.05). Estradiol (but not testosterone) correlated ( r = 0.17, P = 0.01) with prostate volume. The peak flow rate and PSA did not correlate with any endocrinologic parameter. Hypogonadism (serum testosterone less than 3.0 ng/mL) was detected in 22.1% of patients and had no impact on clinical (IPSS, peak flow rate, prostate volume, and PSA level) or endocrine (human luteinizing hormone, human follicle-stimulating hormone, estradiol, prolactin, and DHEA-S) parameters. Conclusions. A number of age-related endocrine changes are seen in elderly men with LUTS. Hypogonadism is seen in approximately one fifth of elderly men with LUTS, but in our study it had no impact on symptom status, PSA level, prostate volume, uroflowmetry, or endocrine parameters.

A randomized prospective study of laser ablation of the prostate versus transurethral resection of the prostate in men with benign prostatic hyperplasia

Objectives. To compare the safety and efficacy of laser ablation of the prostate, one of the minimally invasive treatments available for men with benign prostatic hyperplasia, to transurethral resection of the prostate (TURP). Methods. A prospective randomized study of 100 men with benign prostatic hyperplasia, with 50 patients in each treatment arm, was conducted. All patients met the entry criteria: age older than 45 years, no history of carcinoma of the prostate, a peak flow rate less than 15 mL/s, medical therapy failure, and the ability to undergo regional or general anesthesia. All patients underwent a preoperative evaluation consisting of the American Urological Association (AUA) symptom score, uroflowmetry, pressure-flow study, transrectal ultrasound for prostate volume, and serum prostate-specific antigen determination. Patients underwent either TURP or laser ablation of the prostate using the potassium titanyl phosphate (KTP)/neodymium:yttrium-aluminum-garnet laser. Patients were seen for follow-up at 1, 3, 6, and 12 months. Results. The mean age was 68.2 years (range 45 to 90) for the laser group and 67.4 years (range 54 to 82) for the TURP group. The mean AUA symptom score was 22 for the laser group and 21 for the TURP group. The mean peak uroflow rate was 7.6 ± 3.4 mL/s for the laser group and 6.5 ± 4.0 mL/s for the TURP group. At 12 months of follow-up, the mean AUA symptom score had decreased to 7 (−69.5%) for the laser group and to 3 (−80.9%) for the TURP group. The mean peak uroflow rate increased to 15.4 mL/s (+107.8%) for the laser group and to 16.7 mL/s (+150.7%) for the TURP cohort. Seventy-five percent of the laser group had a 50% or greater decrease in their individual AUA symptom score compared with 93% of the TURP group. Sixty-five percent of the laser cohort had a 50% or greater increase in their peak uroflow rate compared with 75% of the TURP cohort. Conclusions. Laser prostatectomy produced improvements in the peak flow rate and symptom score similar to those produced by TURP. The patients who underwent laser treatment required a longer period to reach maximum improvement, which probably reflects the lack of tissue debulking at the time of surgery. Further improvement in laser technology will be required to produce more immediate results.

THE CHANGING PATTERN OF PROSTATE CANCER AT THE TIME OF DIAGNOSIS: CHARACTERISTICS OF SCREEN DETECTED PROSTATE CANCER IN A POPULATION BASED SCREENING STUDY

Purpose We describe the clinical and pathological features of prostate cancer diagnosed through serum prostate specific antigen (PSA), digital rectal examination and transrectal ultrasonography in a population based randomized screening study. Materials and Methods Between November 1993 and June 1997, 20,632 volunteers 55 to 76 years old were included in the study. In the screening arm 9,776 men underwent digital rectal examination, transrectal ultrasound and serum PSA determination. Biopsies were taken if the digital rectal examination and/or transrectal ultrasound findings were abnormal or if PSA was 4 ng./ml. or greater. A total of 2,262 men underwent biopsy and 474 cases of prostate cancer were diagnosed. Results The pretreatment data were complete in 459 men, of whom 78% had clinically organ confined disease. Bone or lymph node metastases were seen in 8 cases (1.7%). Of 172 men who underwent radical prostatectomy 2 had lymph node metastases. Overall 66.3% of men treated with radical prostatectomy had organ confined disease. Conclusions Comparison of the characteristics of prostate cancer detected through screening of the general population with those in a population based cohort of men in which there was no organized screening revealed stage reduction, primarily with regard to number of metastatic cases. Whether this stage reduction will lead to a decrease in disease specific mortality remains unknown until the study is completed and the end point of prostate cancer specific mortality is evaluated.

Prostate-specific antigen (PSA) in human seminal plasma.

Prostate-specific antigen (PSA) was measured in seminal plasma and serum of 113 men under investigation for involuntary barrenness. PSA in seminal plasma was 0.4 +/- 0.3 (median 0.35) mg/mL and in serum 0.6 +/- 0.5 (median 0.6) ng/mL. The concentrations in these 2 compartments were independent of each other. The determination of PSA in neither blood serum nor seminal plasma brought new essentials for fertility status.

IMMUNIZATION, SCREENING FOR MALIGNANCY AND HEALTH MAINTENANCE IN THE LIVER TRANSPLANT RECIPIENT

196 Transplant recipients are highly motivated to maintain their recovered health status and are generally compliant with pharmacotherapy and medical followup. In addition to routine blood tests, and monitoring of immunosuppressant drug levels, recipients require immunization updates, ongoing screening for malignancy, hypertension, hyperlipidemia, and ophthalmologic complications. Little information is available about the consistent implementation of these health maintenance strategies in this population. Methods: A telephone survey was conducted by two investigators using a standardized 20 item questionnaire to audit the frequency of obtaining routine and specialized screening tests for malignancy, and annual health maintenance screening, as well as knowledge and receipt of immunizations. Sixty liver recipients transplanted at our institution between 1992 and 1996 were contacted. Results: 51% of those surveyed were male and the mean age of all surveyed was 48 years. Pneumococcal and hepatitis B vaccination occurred in 13 and 18%, respectively, of patients prior to transplantation. After transplantation, 27% have received pneumococcal vaccination, and 48% received yearly influenza vaccination. 2 of 60 recipients questioned were aware of the need for varicella immunoglobulin if exposed to chicken pox, or the need for the recipient's children or grandchildren who are undergoing polio vaccination to receive an inactivated polio preparation. Yearly screening for dermatologic or oral malignancies was sought by only 40% of patients. Physician-performed breast exam or screening mammograms to assess for breast pathology was done in 38% of women surveyed. Male recipients received either prostate exams or serum prostate specific antigen determinations, or both, in 68% of those questioned. 30 of 60 recipients had either flexible sigmoidoscopy or colonoscopy within the last two years. Yearly dental evaluations were sought by 75% of patients, and greater than 90% had at least yearly blood pressure and weight determinations. 41 of 60 patients were aware of cholesterol and lipid profiles having been performed within the last two years. Ophthalmologic screening was performed in 83% of recipients surveyed. Conclusions: Our survey suggests that routine health maintenance management is less than ideal in this population. Follow up based on a standard protocol may improve the health status of these patients.

Comparison of serum prostate-specific antigen levels and PSA density in african-american, white, and hispanic men without prostate cancer

Objectives. To determine the influence of race or ethnicity on serum prostate-specific antigen (PSA) levels and PSA density (PSAD) in a population of healthy men without clinically evident prostate cancer. Methods. This retrospective study was conducted between January 1988 and January 1993. The serum PSA levels were measured in 859 men (586 African Americans, 142 whites, and 131 Hispanics) who were participants in a prostate cancer screening program or had urinary symptoms suggestive of prostate gland pathology. All men underwent a detailed clinical examination, including digital rectal examination, serum PSA determination, and transrectal ultrasound (TRUS). None of the subjects included had clinical or TRUS evidence of prostate cancer (furthermore, 283 men were pathologically proved to be cancer-free by prostate biopsies). Serum PSA levels and PSA densities as a function of each individdual's ethnic background were determined. Results. The mean serum PSA level in African Americans was 2.1 ng/mL, which was significantly higher than that of whites (mean PSA of 1.53 ng/mL) and Hispanics (mean PSA of 1.83 ng/mL) ( P = 0.003). Similar differences among the three groups were observed in PSA density (the mean PSAD was 0.078, 0.057, and 0.065 for African Americans, whites, and Hispanics, respectively). A separate analysis for the biopsy-negative men was performed, and the findings were consistent with the observations for the entire study group. After adjustment for age and prostate volume, the differences remained statistically significant. Conclusions. Among men without evidence of prostate cancer, African Americans have higher serum PSA levels and PSA densities than do whites or Hispanics. Race or ethnicity was an independent factor that affected serum PSA levels even after adjustment for age and prostate volume.

Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer

Background and purpose: To determine the kinetics of serum prostate-specific antigen (PSA) after radiation therapy of localized prostate cancer and to evaluate whether such kinetics provide prognostic information. Materials and methods: Eight hundred forty-one men with serial PSA determinations who underwent external beam radiation without androgen ablation were analyzed to determine postradiation PSA kinetic parameters (half-life and doubling time) and to correlate these parameters with disease outcome. Non-linear regression techniques were used to determine half-lives and doubling times. Results: The postradiation serum PSA data fitted well to first order kinetic models. The median PSA half-life was 1.6 months (range 0.5–9.2 months). There was no correlation between half-life and T-stage or Gleason grade. A significant but quantitatively weak correlation was present between the pretreatment PSA level and half-life; lower pretreatment levels were associated with longer half-lives. Half-life did not correlate with disease outcome whether the endpoint was local recurrence, distant metastasis or rising PSA. In 263 men with a rising postradiation PSA profile the median PSA doubling time was 12.2 months (range 0.8–80.2 months). Faster doubling times were significantly associated with higher T-stage, higher Gleason grade and higher pretreatment PSA levels. Thus, patients with initially adverse disease developed faster rising PSA values after treatment than patients with less adverse disease. The most striking correlation was between rapid doubling time and the likelihood of metastatic relapse. Patients who developed metastases had a median PSA doubling time of 4.2 months compared to a median doubling time of 11.7 months in patients who developed local recurrence. Overall, patients with a PSA doubling time of less than 8 months had a 7-year actuarial metastatic rate of 54%, while patients with a PSA doubling time exceeding 8 months had only a 7% metastatic rate. Particularly ominous was the combination of a doubling time shorter than 8 months which began to rise within the first year; by 3 years 50% of these men had metastases and all were actuarially projected to develop such relapse by 6.5 years. Conclusions: Overall, the clinical utility of postradiation serum PSA kinetics was small. There were no discernible uses for PSA half-life. In patients with a rising PSA profile the faster the kinetics the more adverse the disease. Doubling times shorter than 8 months, especially if the rise begins in the first year, predict for metastatic relapse. However, in the absence of decisively useful treatment for metastatic prostate cancer the virtues of the early detection of metastases remain unclear.

Prostate-specific antigen levels from a mass screening program using highly sensitive RIA kits.

This study was designed to evaluate the distribution of prostate-specific antigen (PSA) levels of men in a mass screening program for prostatic disease. A total of 763 men over 40 years of age underwent mass screening for prostatic disease in a Japanese prefecture using the highly sensitive Eiken kit and the Hybritech (Tandem-R) kit. The screening tests consisted of serum PSA determination, digital rectal examination, a questionnaire on symptoms, evaluation of prostate volume, and determination of the obesity rate. Serum PSA levels of all subjects were measured with both kits. The correlation between the values obtained by the Eiken kit and those of the Tandem-R kit was high (r = 0.990), but the values of the former were slightly higher than those of the latter. Serum PSA weakly correlated with age, however, when estimated within decade age brackets, the levels of PSA showed significant differences among only 1 pair of groups stratified by age. In contrast, the levels of PSA showed significant differences among 9 pairs of groups stratified by prostate volume. A highly sensitive assay kit is useful to evaluate both the distribution of PSA levels and the relationship of PSA values to age and prostate volume of men in mass screening programs for prostatic disease, since approximately 40% of the subjects who underwent the present mass screening showed PSA values under 1.0 ng/mL, which have been the the lower limit of detection of many PSA kits.

Prostate-specific antigen in men born with bladder exstrophy

Objectives To determine serum levels of prostate-specific antigen (PSA) in men born with bladder exstrophy and to investigate the clinical utility of this test in the bladder exstrophy population. Methods Ten men aged 19 to 45 years with a history of bladder exstrophy underwent digital rectal examination and free and total serum PSA determinations. Immunohistochemistry for PSA and prostate-specific acid phosphatase (PSAP) was performed on archival prostate tissue from 1 man with bladder exstrophy. Results Free and total serum PSA levels for all patients were measurable and below the upper limit for established age-specific reference ranges for normal men. Both PSA and PSAP were detectable by immunohistochemistry in prostate epithelial cells of a man with bladder exstrophy. Conclusions Men born with bladder exstrophy have detectable serum PSA levels. However, because prostate cancer in men with bladder exstrophy has not been reported, whether PSA will have a clinical role as a serum tumor marker for prostate cancer in this population remains to be determined. If so, the PSA reference range for men with the exstrophy condition will need to be defined. Because prostate histology in men with exstrophy resembles that of normal men, careful clinical monitoring for benign and malignant tumors should not be overlooked in this particular population.

PSA‐based screening for prostate cancer in asymptomatic younger males: Pilot study in blood donors

BACKGROUND The efficacy and success of a screening program for prostate cancer in young and healthy asymptomatic volunteers are described. METHODS In the present study, prostate specific antigen (PSA) samples obtained from 2,272 males (aged 40–65 years) who donated blood at the local Red Cross Blood Bank were evaluated. Two groups of donors were distinguished, which were investigated in different ways. Group 1 comprised individuals aged 40–49 years (n = 568), while group 2 consisted of males aged 50–65 years (n = 1,704). Volunteers in group 2 who had PSA levels greater than 4 ng/ml (n = 302) were referred for ultrasound guided biopsy irrespective of findings on digital rectal examination (DRE). In group 2, individuals with PSA levels exceeding 4 ng/ml and positive DRE findings biopsy specimen was ordered (n = 2). In patients with unremarkable findings on DRE, serum PSA was determined 1 year later and in case of more than 20% increase in the PSA level biopsy was obtained under ultrasound guidance. RESULTS The biopsy specimen yielded prostatic carcinoma in 58 patients in group 1. As a screening test, serum PSA determination was superior to digital rectal examination. On digital palpation only 2 presented with abnormal prostates. These 58 patients underwent radical prostatectomy and histological examination revealed organ-confined disease in all but 8. In group 2, in 4 of 12 males the biopsy specimen yielded prostatic carcinoma. CONCLUSIONS This study shows that PSA measurement in blood donors is a useful method for recruiting screening volunteers, and therefore represents an additional possibility for early detection of prostate cancer in asymptomatic younger males. Furthermore, it represents an effective tool for following relatively young patients known to have a significant risk of prostate cancer. Prostate 30:20–25, 1997 © 1997 Wiley-Liss, Inc.

PSA-based screening for prostate cancer in asymptomatic younger males: pilot study in blood donors.

The efficacy and success of a screening program for prostate cancer in young and healthy asymptomatic volunteers are described. In the present study, prostate specific antigen (PSA) samples obtained from 2,272 males (aged 40-65 years) who donated blood at the local Red Cross Blood Bank were evaluated. Two groups of donors were distinguished, which were investigated in different ways. Group 1 comprised individuals aged 40-49 years (n = 568), while group 2 consisted of males aged 50-65 years (n = 1,704). Volunteers in group 2 who had PSA levels greater than 4 ng/ml (n = 302) were referred for ultrasound guided biopsy irrespective of findings on digital rectal examination (DRE). In group 2, individuals with PSA levels exceeding 4 ng/ml and positive DRE findings biopsy specimen was ordered (n = 2). In patients with unremarkable findings on DRE, serum PSA was determined 1 year later and in case of more than 20% increase in the PSA level biopsy was obtained under ultrasound guidance. The biopsy specimen yielded prostatic carcinoma in 58 patients in group 1. As a screening test, serum PSA determination was superior to digital rectal examination. On digital palpation only 2 presented with abnormal prostates. These 58 patients underwent radical prostatectomy and histological examination revealed organ-confined disease in all but 8. In group 2, in 4 of 12 males the biopsy specimen yielded prostatic carcinoma. This study shows that PSA measurement in blood donors is a useful method for recruiting screening volunteers, and therefore represents an additional possibility for early detection of prostate cancer in asymptomatic younger males. Furthermore, it represents an effective tool for following relatively young patients known to have a significant risk of prostate cancer.

Predictive Properties of Serum Prostate-Specific Antigen Testing in a Community-Based Setting

Most studies that have described the sensitivity and specificity of prostate-specific antigen (PSA) as a screening test have been conducted in urology practice settings or in media-based screening programs. The control patients from these settings may have a higher prevalence of urologic disorders that increase serum PSA levels than that of the general population in which screening efforts might take place, leading to biased estimates of sensitivity and specificity. To determine the sensitivity and specificity of serum PSA levels for the early detection of prostate cancer in a population-based setting. This population-based case-control study was conducted in Olmsted County, Minnesota, where the Rochester Epidemiology Project could identify all incident cases of prostate cancer through passive surveillance of medical care provided to local residents. Case patients were all 177 men (age range, 50-79 years) who were newly diagnosed as having prostate cancer from 1990 through 1992 and had a prediagnostic serum PSA determination (90% of all incident cases). Control patients were randomly selected from the Olmsted County population and had undergone a clinical examination to exclude prostate cancer. The median (25th and 75th percentiles) of serum PSA levels was 9.4 ng/mL (5.4 and 18.6 ng/mL, respectively) for case patients and 1.2 ng/mL (0.7 and 2.1 ng/mL, respectively) for control patients (P < .001). When sensitivity was plotted against 1-specificity, the area under the receiver operating characteristic curve was 0.94 (SE, 0.01). The predictive power declined somewhat with age, with areas under the curve of 0.96, 0.94, and 0.90 for men in their 50s, 60s, and 70s, respectively. When cases were restricted to the 155 men with clinically localized disease, the area under the curve was essentially unchanged (0.94; SE, 0.01) and still much greater than the estimates of 0.75 that were reported from urology practice- and media-based settings. In a community-based setting, serum PSA levels provide better discrimination between men with and without clinically localized prostate cancer than has been observed in studies that were conducted in urologic practices. These results suggest that previous decision analyses may have underestimated the predictive value of PSA for the detection of prostate cancer in a primary care or community-wide screening program.

Serum Prostate-Specific Antigen Concentration before and after Vasectomy

Recent epidemiologic studies have suggested that a risk factor for the development of carcinoma of the prostate may be previous vasectomy. As a majority of prostate cancer cases diagnosed in the U.S. are detected by an elevation in prostate-specific antigen (PSA), an elevation in PSA due to vasectomy may underpin this association. There have been no published reports on the relationship between PSA before and after vasectomy. To study this relationship, this study was undertaken to determine the effects of vasectomy on PSA. Twenty-five men undergoing vasectomy were studied with serial PSA determinations prior to and following vasectomy. Analysis of data suggests that PSA is not affected by previous vasectomy and that other causes for an increased detection in this cohort may be operational.

Ejaculation increases the serum prostate-specific antigen concentration

To determine the effect of ejaculation on the serum prostate-specific antigen (PSA) concentration in men at risk for developing prostate cancer. A prospective, community-based study was conducted in which 64 men, aged 49 to 79 years, underwent a serum PSA determination immediately before ejaculation (baseline) and at 1 hour, 6 hours, and 24 hours following ejaculation. The serum PSA also was measured 48 hours and 1 week after ejaculation if the concentration had not returned to the baseline value by the previous time interval. All subjects abstained from ejaculation for a minimum of 7 days prior to the study and until the PSA concentration returned to the baseline level. Absolute and relative change in serum PSA concentration, as well as the time to return to baseline PSA concentration following ejaculation, were assessed. The serum PSA concentration increased following ejaculation in 87% of the subjects. The mean baseline PSA was 1.8 ng/mL (median, 0.7 ng/mL). The mean absolute PSA change +/- standard deviation 1 hour, 6 hours, 24 hours, and 48 hours after ejaculation was 0.8 +/- 1.32 ng/mL, 0.3 +/- 0.66 ng/mL, 0.2 +/- 0.33 ng/mL, and 0.4 +/- 0.40 ng/mL, respectively. The mean relative PSA change +/- standard error 1 hour, 6 hours, 24 hours, and 48 hours after ejaculation was 41 +/- 4%, 9 +/- 1.5%, 8 +/- 1.3%, and 10 +/- 2.3%, respectively. The absolute and relative changes in PSA concentration noted 1 hour, 6 hours, and 24 hours after ejaculation were statistically significant (P = 0.0001). A strong correlation was observed between absolute change in PSA and baseline serum PSA, at each time interval (1 hour: r = 0.68, 6 hours: r = 0.77, 24 hours: r = 0.70; P < 0.0001) after ejaculation. Similarly, a significant correlation was noted between absolute change in PSA and patient age at each time interval (1 hour: r = 0.37, 6 hours: r = 0.38; P = 0.002, 24 hours: r = 0.55; P < 0.0001). Ninety-two percent of subjects returned to baseline by 24 hours (95% confidence interval (Cl) = 83% to 97%), whereas 97% of subjects returned to baseline by 48 hours (95% Cl = 89% to 99%). Ejaculation causes a significant increase in the serum PSA concentration in men between 49 and 79 years of age that may persist for up to 48 hours. This change appears to correlate with age and baseline PSA. It is recommended that men abstain from ejaculation for 48 hours prior to having a serum PSA determination.

Procollagen type I carboxyterminal extension peptide in serum: a reliable marker of bone metastatic disease in newly diagnosed prostate cancer?

This study evaluates the accuracy of type I procollagen, a bone matrix glycoprotein, and prostate-specific antigen (PSA) as markers for predicting the results of radionuclide bone scan in newly diagnosed, previously untreated patients with prostate cancer. 74 patients underwent serum PSA and procollagen determination using specific antibodies. A staging radionuclide bone scan was then performed; patients with positive bone scan were submitted to x-rays of the suspicious zones. Then, we calculated sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of procollagen and PSA in the detection of bone metastases. Procollagen alone had 83.3% sensitivity, 96% specificity, 90.9% positive predictive value, 92.3% negative predictive value and 91.9% overall accuracy. PSA alone had 70.1% sensitivity, 86% specificity, 70.8% positive predictive value, 86% negative predictive value and 81.1% overall accuracy. According to our data, we no longer perform a staging radionuclide bone scan in patients with PSA < 20 ng/ml and normal procollagen level, diminishing the number of radionuclide bone scans and increasing the overall net savings for the health care system.

Serial Prostate Specific Antigen Measurements and Progression in Untreated Confined (Stages T0 to 3NxM0, Grades 1 to 3) Carcinoma of Prostate

Purpose The contribution of serial prostate specific antigen (PSA) determinations was studied to obtain understanding of the natural history of clinically confined prostate carcinoma. Materials and Methods Serial PSA determinations in 29 patients with untreated confined prostate carcinoma were correlated to the clinical course for a mean of 39 months. Results Disease progressed locally in 13 patients after a mean of 31 months. Metastatic progression was not observed. Neither grade, stage, PSA changes nor initial PSA showed significant differences with respect to interval of progression between patients with and without progression. Conclusions PSA does not parallel clinical progression in patients selected for watchful waiting.

Derivation and application of upper limits for prostate specific antigen in men aged 50-74 years with no clinical evidence of prostatic carcinoma.

To derive age-specific upper limits for prostate specific antigen (PSA) level in men 50-74 years of age with no clinical evidence of prostatic carcinoma, and to test the sensitivity and specificity for cancer detection of these upper limits. A total of 6166 men were recruited for a multicentre study of prostate cancer detection and underwent a serum PSA determination and digital rectal examination (DRE). Men considered to be clinically free of prostatic carcinoma were those with a normal DRE and a PSA level < or = 4.0 ng/mL, and men with an abnormality in either parameter who underwent ultrasonography-guided prostate biopsy that revealed no evidence of carcinoma. By these criteria, 5469 men had no evidence of prostatic carcinoma. Dividing the population into 5-year age increments, three statistical methods were assessed to derive upper limits for serum PSA level by age; the mean +2 SD, the 99th percentile, and a 97.5% prediction interval based on linear regression. Newly-derived upper limits calculated by each method in the 50-54 and the 70-74 age group were 3.9 ng/mL and 7.6 ng/mL (mean +2 SD), 5.2 ng/mL and 14.0 ng/mL (99th percentile), and 4.7 ng/mL and 8.2 ng/mL (97.5% prediction interval). The sensitivity of the newly-derived upper limits was tested using receiver operating characteristic curves derived from men with no suspicious findings on DRE and a serum PSA concentration > 4.0 ng/mL. Although the specificity of the test increased with increasing PSA upper limits, no upper limits derived from these three methods yielded adequate sensitivity to detect cancer; sensitivities by age range were from 53 to 94%, using mean +2 SD, from 25 to 50% with the 99th percentile, and from 47 to 64% with the 97.5% prediction interval. We do not recommend age-referenced adjustments in upper limits for serum PSA concentration, but recommend that an upper limit of 4.0 ng/mL be used in all men 50-74 years of age.

Serum prostate-specific antigen and the biologic progression of prostate cancer.

We have previously shown that serum prostate-specific antigen (PSA) is proportional to prostate cancer volume and that progression of prostate cancer is proportional to volume, but other investigators have not found serum PSA to be as useful in predicting pathologic stage at the time of radical prostatectomy. Because our series is the only study to examine prospectively all radical specimens at 3-mm intervals, we have examined the relationship between serum PSA and the morphologic indicators of cancer progression in our first 350 radical prostatectomies. Preoperative serum PSA level was tabulated in 350 consecutive patients with prostate adenocarcinoma and compared with morphologic variables in the radical prostatectomy specimen. Morphologic variables included cancer volume, histologic grade, capsular penetration, seminal vesicle invasion, and lymph node metastasis. Serum PSA showed strong correlation with all morphologic variables, which were highly intercorrelated. Serum PSA level was strongly correlated with cancer volume, histologic grade, and frequency of regional spread to lymph nodes. Close intercorrelations found between all variables were translated into a scale relating each level of serum PSA elevation to stage of disease in morphologic terms. Using this scale, serum PSA level can contribute to patient evaluation and treatment decisions in men with prostate cancer. Serum PSA is primarily determined by prostate cancer volume and secondarily by the percentage of high-grade cancer (Gleason grades 4 and 5) in the prostate. Because of this basic relationship, serum levels of PSA provide a clinically useful estimate of morphologic findings in the prostate. Serial PSA determinations should reflect the growth of the cancer as well as the gradual evolution of more malignant cells with the passage of time. The use of a serum PSA-based rating scale can contribute to patient evaluation and treatment decisions in men with prostate cancer.