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Biomedical subjects

M K Brawer

Publications and source records attributed to M K Brawer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Transition zone prostate specific antigen density: lack of use in prediction of prostatic carcinoma.

PURPOSE: Among the new approaches to enhance the performance of prostate specific antigen (PSA) testing in a biopsy population is the use of the free-to-total PSA as well as the transition zone density, which is calculated by dividing the PSA by the transition zone volume. We compare these manipulations of the PSA to PSA alone in a biopsy population. MATERIALS AND METHODS: We evaluated 917 consecutive men who underwent ultrasound guided biopsy for an elevation in serum PSA or abnormality on digital rectal examination. Total PSA was measured using the Tandem-E or Tandem-R method. Prostate gland volume and transition zone were measured with ultrasound and calculated using the prolate ellipsoid formula. RESULTS: In the overall PSA range 276 men had carcinoma (30.0% of the population), while in the PSA 4.0 to 10.0 ng./ml. range 141 of 477 had cancer (29.6%). Receiver operating characteristics analysis and analysis of variance were performed. In the overall PSA series the Tandem total PSA performed as well as any PSA index to predict carcinoma. In the restricted range of total PSA 4.0 to 10.0 ng./ml. total PSA density as well as transition zone density were more predictive than PSA alone. In both PSA ranges the volume of benign glands was significantly larger than in the prostates exhibiting carcinoma. There was no statistically significant difference in outcomes of analyses between different investigators or different sites of investigation (Veterans Affairs versus university based hospitals). CONCLUSIONS: In this biopsy population transition zone PSA density did not add to the information available with total PSA and gland volume. Neither investigator nor site bias contributed to the failure of transition zone PSA density or PSA density to predict prostatic carcinoma.

Adult↗
PubMed1998

Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer.

PURPOSE: We reviewed the use of percent free prostate specific antigen (PSA) to enhance specificity of PSA testing and aid in the discrimination of benign and malignant prostate disease. We present proposed percent free PSA cut points and probability factors, and discuss factors that are believed to affect study outcomes and conclusions. MATERIALS AND METHODS: We reviewed the literature with respect to PSA and free PSA with particular emphasis on clinical use of percent free PSA and factors that may affect study outcomes. RESULTS: Percent free PSA may increase the specificity of PSA testing without sacrificing the cancer detection rate. Differences in study designs and subject populations may account for the confusion in the current literature. Specific factors that may influence study outcomes include sample size, PSA range, age, race, digital rectal examination findings, prostate size, tumor size and pathology, as well as treatment history, sample collection and storage conditions, and the particular assays used to determine free and total PSA values. CONCLUSIONS: The use of percent free PSA to enhance the specificity of prostate cancer screening is thought to provide useful information to aid in the differentiation of benign and malignant prostate diseases. There is evidence to suggest a benefit cost advantage to a tailored biopsy approach based on percent free PSA. However, statistically valid multisite clinical trials that take into account influencing factors are needed to set assay specific cut points and probability determinations.

Age Factors↗
PubMed1998

Measurement of complexed PSA improves specificity for early detection of prostate cancer.

OBJECTIVES: Prostate-specific antigen (PSA) is the most useful of all tumor markers. Although the sensitivity is impressive, low specificity results in a lack of cancer detection in a significant proportion of patients undergoing prostate biopsy. Several recent studies have addressed the need for improved specificity. Of all these approaches, the free/total PSA ratio appears to be the most promising. Given that most circulating PSA is complexed to alpha1-antichymotrypsin, and that this moiety represents a greater proportion of the total PSA in those men with carcinoma, we set out to determine whether complexed PSA would improve specificity in the detection of men with prostate cancer. METHODS: Archival sera were obtained from 300 men, 75 of whom had biopsy-proved prostate cancer. All sera had been previously stored at -70 degrees C for variable periods. An investigative assay for complexed PSA (Bayer) was used. The Tandem-R free and total PSA assays (Hybritech) were used according to the manufacturer's recommendations. RESULTS: Among all patients, specificities for the total PSA, free/total PSA, and complexed PSA alone were 21.8%, 15.6%, and 26.7%, respectively, at cutoffs yielding 95% sensitivity. Similar equivalence or superior performance, in terms of specificity relative to the free/total PSA ratio, was seen at other sensitivity thresholds and other total PSA ranges. CONCLUSIONS: Complexed PSA alone performs better than total PSA or the free/total PSA ratio and obviates the need for a second analyte determination. We believe this marker may offer significant enhancement in PSA testing with significant economic advantages.

Aged↗
PubMed1998

Management of radiation failure for localized prostate cancer.

Due to the historically large number of patients with localized prostate cancer (CAP) treated by radiation therapy, an increasing number of patients are presenting local failure. The currently available concepts regarding its definition as well as management options are reviewed. The literature regarding radiation failure for localized prostate cancer was reviewed. Emphasis was made on articles concerning definition of radiation failure, patient evaluation and restaging and definitive as well as palliative management options. There is definitely a subset of patients with locally recurrent prostate cancer without evidence of metastasis that could potentially benefit from aggressive local therapy. A treatment algorithm is proposed but it should be emphasized that treatment options should be individualized to suit the need of a particular patient.

Journal Article↗
PubMed1998

Prospective evaluation of percent free-PSA and complexed-PSA for early detection of prostate cancer.

Aims of the study: Retrospective studies investigating the use of percent free-PSA for early detection of prostate cancer were limited for various reasons: by their use of long-term stored sera, poor mix of non-cancer to cancer cases and the use of only men with PSA values between 4.0 and 10.0 ng/mL. This prospective study investigates the clinical utility of percent free-PSA and complexed-PSA for early detection of prostate cancer in 219 consecutive men presenting for prostate biopsy. Methods: Of 246 consecutive men who underwent ultrasound guided sextant biopsy of the prostate for PSA elevation and/or suspicious digital rectal exam, 219 men had serum total PSA levels between 2.0 and 20.0 ng/mL and were included in this study. Serum total, free and complexed (PSA-ACT) were measured (Hybritech Inc.). Results: Pathologic examinations demonstrated that 72% and 28% of the biopsies were non-cancer and cancer respectively. The mean percent free-PSA was statistically different between the groups (cancer 14%+/-6.4 and non-cancer 18+/-9%, P<0.001) and improved cancer detection. PSA-ACT provided only modest improvement in cancer detection over that of total PSA. Among this cohort of men, the optimal total PSA reflex range for percent free-PSA was 3.0-7.0 ng/mL (38% specificity) with a percent free-PSA cut-off of 20% (95% sensitivity) yet only affected 56% of the cases. Conclusions: PSA-ACT added very little additional value to the clinical utility of total PSA for early detection. Percent free-PSA performed well for all reflex ranges. A sensitivity and specificity of 95% and 20% respectively were obtained using a single cut-off of 25% for percent free-PSA for the group of men with total PSA values between 4.0 and 10.0 and correlated well with recently reported prospective analyses.

Journal Article↗
PubMed1998

A comparison of three free and total PSA assays.

Prostate-specific antigen (PSA) has emerged as the most predictive test of whether or not a man has prostatic carcinoma. The free to total PSA ratio provides important enhancement in specificity, thus obviating unnecessary negative biopsies. In the absence of an international standard for total PSA, much less free PSA, variation between manufacturers may cause confusing results. We sought to compare three different manufacturer's free and total PSA assays in a population consisting of consecutive patients who had PSA testing in a reference laboratory in Germany. Between April 1994 and July 1996, serum specimens from 240 men were evaluated with three different free and total PSA assays. Indications for PSA determination were based on the referring physician, who also provided the clinical diagnosis. Total and free PSA were measured on the same freeze-thaw cycle with Chiron Diagnostics, Enzymun Boehringer Mannheim, and Hybritech Tandem-R assays. Seventy-nine men had carcinoma of the prostate, 120 had clinical evidence of benign prostatic hyperplasia and 27 were without evidence of prostatic disease. The Chiron ACS: 180 free to total ratio compared very well with the Tandem-R assay at the 95% sensitivity level, affording 17 and 22% specificity respectively. Using the range of total PSA of 4-10 ng/ml, the increase in specificity of the free to total PSA is quite significant, and the specificity of the Enzymun assays is greatly improved. (Specificity of 49%, 29% and 25% at 95% sensitivity for ACS, Enzymun and Tandem respectively.) This data, based on 'real world' clinical experience, shows significant variation between different manufacturers' assays. There was significant equivalence between the Chiron and Hybritech assays. The Enzymun assay performed well only when data from the total PSA range of 4-10 ng/ml was included. Clinicians must be aware of which manufacturers' assays for both the free and total PSA their laboratory staff is utilizing, and laboratory technicians must provide meaningful outcome data based on the patient population they serve with respect to the performance of these assays.

Journal Article↗
PubMed1998

Comparison of 3 investigational assays for the free form of prostate specific antigen.

PURPOSE: Measuring percent free/total prostate specific antigen (PSA) versus total PSA alone has been shown to enhance the stratification of cases with and without prostate cancer. We compared the diagnostic performance of 3 free PSA assays when values were interchanged over a common total PSA denominator. MATERIALS AND METHODS: Archival sera from 123 consecutively accrued patients (25 with prostate cancer, 98 with no evidence of malignancy) who had pre-biopsy total PSA levels from 2.0 to 20.0 ng./ml. were obtained from our specimen bank. Serum specimens were analyzed using the Hybritech Tandem R, Dianon Systems and Chiron ACS 180 free PSA assays. Total PSA was measured using the Hybritech Tandem R total PSA assay. Linear regression was performed to evaluate the correlation and agreement among assays. Sensitivity and specificity of cancer detection were calculated to compare diagnostic performance. RESULTS: The required percent free PSA cutoffs were different among the 3 free PSA assays. The cutoffs to ensure a 95% sensitivity of cancer detection were 22, 34 and 34%, and the number of negative biopsies that were prevented at these cutoffs (specificity) was 38, 19 and 33% for the Hybritech, Dianon, and Chiron assays, respectively. CONCLUSIONS: The results among the different assays were not interchangeable. Clinicians should be aware that different percent free PSA cutoffs need to be used based on the type of free and total PSA assays, and that not all assays diagnostically perform the same.

Aged↗
PubMed1998

The effect of prostate volume on the yield of needle biopsy.

PURPOSE: Early diagnosis of prostate carcinoma has undergone significant evolution mainly due to the widespread use of serum prostate specific antigen, transrectal ultrasonography and spring loaded biopsy devices. A common dilemma faced by clinicians arises when a negative biopsy is obtained in a patient and there is a high suspicion for prostate carcinoma. The literature reveals a 20 to 40% positive repeat biopsy rate in men with elevated prostate specific antigen who had an initial negative biopsy. We determined the yield of 6 systematic sector biopsies as a function of total gland and peripheral zone volumes. MATERIALS AND METHODS: The database of transrectal ultrasound guided prostate needle biopsies performed at the Department of Urology, University of Washington Medical Center and Veterans Affairs Puget Sound Health Care System was reviewed. The yield of the 6 biopsies was determined as a function of the total gland and peripheral zone volumes. RESULTS: A total of 1,057 men who underwent transrectal ultrasound guided prostate needle biopsies were investigated in our study. Of the men 326 were diagnosed with prostate cancer for a positive biopsy rate of 30.8%. No relationship between gland size and cancer yield was seen using total gland volume compared to the first quartile until the largest quartile when a significantly lower cancer detection rate was noted (odds ratio 1.5). CONCLUSIONS: The positive yield of the systematic 6-sector biopsy decreases significantly when the total gland volume is greater than 55.6 cc or peripheral zone volume is greater than 33.61 cc. In men with smaller prostates 6 systematic sector biopsies should be adequate.

Adult↗
PubMed1997

Histologic differences in benign prostate hyperplasia between Chinese and American men.

BACKGROUND: This investigation sought to determine morphologic differences between Chinese and Americans with symptomatic benign prostatic hyperplasia (BPH), in an admixture of stroma, epithelium, and luminal spaces. METHODS: Adjacent sections of simple prostatectomy specimens from China and the U.S. were stained to highlight the stroma and epithelium. Image analysis was performed on random fields. RESULTS: Chinese tissue had higher glandular densities (mean = 12.5 acini/mm2 vs. 6.2 acini/mm2; P < 0.0001), while American samples had higher percent stroma (mean = 66% vs. 51%; P = 0.0003). Mean luminal cell heights in the Chinese and American prostate acini were 11.7 and 19.0 microns, respectively (P < 0.0001). CONCLUSIONS: These data indicate significant histologic variation in BPH between Chinese and American men undergoing simple prostatectomy. These differences may provide a focus for investigating the epidemiological variation in clinical BPH and carcinoma between our two countries, and could have applications in clinical management of symptomatic BPH.

Aged↗
PubMed1997

Comparison of three commercial PSA assays: results of restandardization of the Ciba Corning method.

BACKGROUND: Consistency in prostate-specific antigen (PSA) quantitation by different PSA test manufacturers would minimize potential clinical confusion. The Ciba Corning ACS PSA2 calibration has been adjusted for alignment with a proposed international standard and clinical concordance with the Hybritech Tandem R assay. Herein we evaluate the clinical effectiveness of this recalibrated PSA test by comparing it with the IMx (Abbott Laboratories) and Tandem R (Hybritech) assays. METHODS: Archival serum was used that had been stored at -70 degrees C from men who underwent ultrasound-guided prostate needle biopsy. Assays were run according to each manufacturer's specifications in singlicate on a single thaw. RESULTS: The study included sera of 191 patients; 44 of the patients had carcinoma. There were 151 men with PSA (Tandem R) in the range of 0-10.0 ng/ml, 28 of whom had cancer. The correlation coefficients for Tandem R versus ACS, Tandem R versus IMx, and ACS versus IMx were 0.958, 0.955, 0.979 for benign patients and 0.960, 0.954, and 0.985 for those with cancer, respectively. The corresponding slopes were 1.029, 0.855, and 0.824 for men without and 1.044, 0.830, and 0.790, respectively, for those with malignancy. CONCLUSIONS: These data demonstrate substantial equivalence of the restandardized ACS assay and of the Hybritech method. Significant bias exists between these methods and the IMx assay with lower results being identified with the latter. These findings have significant implication, particularly in screening when results of an IMx assay are compared to other assays.

Evaluation Studies as Topic↗
PubMed1997

Temporal trends in rates of prostate cancer: declining incidence of advanced stage disease, 1974 to 1994.

PURPOSE: We examined the temporal trends in prostate cancer incidence and mortality rates in the Seattle-Puget Sound region. MATERIALS AND METHODS: Prostate cancer incidence and treatment data collected by the Cancer Surveillance System, part of the Surveillance, Epidemiology, and End Results program, were analyzed for temporal trends in disease and treatment. Analyses were restricted to white and African-American men 35 years or older residing in the 13-county area of northwestern Washington state and diagnosed between 1974 and 1994. Data for the treatment analyses were limited to the time period 1983 through 1992. RESULTS: Incidence of prostate cancer increased slowly from 1974 (169/100,000) to 1984 (230/100,000) and then rapidly to a peak in 1991 (486/100,000) before declining (293/100,000 in 1994). Mortality increased from 49/100,000 in 1974 to 67/100,000 in 1994. All stages of prostate cancer followed the same incidence trend peaking in 1991, except distant stage disease, which peaked in 1986 and subsequently declined by over 60% (p <0.001). Proportions of men undergoing radical prostatectomy increased from 1983 to 1992 with the biggest increase in men under 65 years old. CONCLUSIONS: The incidence rate of prostate cancer in the Seattle-Puget Sound region is higher than the rate in some other regions of the country. This is likely due to widespread, more intense prostate specific antigen screening of the population in this region compared to other areas of the country. The incidence rate of prostate cancer in the Seattle-Puget Sound region has peaked and is now declining.

Adult↗
PubMed1997

Biological variation of prostate specific antigen levels in serum: an evaluation of day-to-day physiological fluctuations in a well-defined cohort of 24 patients.

PURPOSE: We evaluated the daily biological variation of serum prostate specific antigen (PSA) concentrations to determine the critical difference required between 2 consecutive PSA measurements that would indicate a significant elevation. MATERIALS AND METHODS: A total of 24 men, grouped according to clinical diagnosis and PSA, underwent phlebotomy for 10 consecutive weekdays. Duplicate serum samples were measured using 3 separate lots of Tandem-E and IMx PSA assays. The biological variation was calculated and the 2 PSA assay systems were compared. The critical difference was examined to determine the percent elevation necessary to indicate (with 95% confidence) that PSA had increased beyond what would be expected from biological and analytical variation. RESULTS: The biological variation, defined in terms of percent coefficient of variation, had a log-normal distribution with a geometric mean of 7.3% coefficient of variation and a 95th percentile value of 19.2% coefficient of variation using the Tandem-E PSA assay. Assuming an analytical variation of 5% coefficient of variation, the median critical difference was 20.5% and the 95th percentile critical difference was 45.8%. There was no significant difference between the 2 PSA assay systems in biological variation. However, PSA concentrations measured by the IMx assay were consistently lower compared to values measured by the Tandem-E assay. CONCLUSIONS: Characterizing the biological variation of serum PSA assists in evaluating the significance of changes in serial PSA measurements. The degree of biological variation differs among patients, such that an increase between 2 consecutive PSA levels that is less than 20 to 46% may be due to biological and analytical variation. These data influence interpretation of repeated measurements of serum PSA with time.

Aged↗
PubMed1997

Prostate cancer.

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Humans↗
PubMed1997

Development of a decision-making tool to predict risk of prostate cancer: the Cancer of the Prostate Risk Index (CAPRI) test.

OBJECTIVES: To provide a simple and reliable clinical prediction for an individual patient's overall risk of cancer at biopsy by deriving an easily implemented test based on a generalizable model. Four variables are analyzed for inclusion in the model: prostate-specific antigen (PSA) level, digital rectal examination (DRE) results, race, and age. METHODS: Two populations were used to develop and validate the test: a model (n = 633) and an independent, geographically separate, external population (n = 766). Pathology records for patients who underwent prostate biopsy between 1991 and 1995 were reviewed and screened for the presence of PSA and DRE results. Records where age and race could be determined were extracted. Multiple logistic regression was used with an iterative approach to optimize each test factor. The Wald chi-square test, receiver operating characteristic (ROC) curve, and Hosmer-Lemingshaw test were used to evaluate the model's predictive capability in the two populations. RESULTS: The model and external populations were significantly different for racial mix, PSA level, age, and biopsy detection rate, providing diverse populations to validate the test. Within a combined model, PSA, DRE, race, and age all demonstrated independent capability to predict cancer at biopsy. Predictive power of the overall test was high within the model population (ROC 80.8%), with minimal loss of power in the external population. The test demonstrated no significant lack of fit in either population. CONCLUSIONS: Within a combined test, PSA, DRE, race, and age all contribute significantly to prediction of prostate cancer at biopsy in an individual patient. The test depicts individual risk in an easily understood, visually provocative manner and should assist the clinician and patient in reaching a decision as to whether biopsy is appropriate.

Age Factors↗
PubMed1997

The relation of p53 protein nuclear accumulation and angiogenesis in human prostatic carcinoma.

All neoplasms require angiogenesis and resulting neovascularity for growth beyond 1 mm(2). Quantitative microvessel density (MVD) has been shown to provide staging and prognostic significance in human prostate cancer (CaP). recently, it has been demonstrated that loss of the wild-type allele of the p53 tumour suppressor gene results in reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. There is also an increased expression of vascular endothelial growth factor which promotes neovascularization. p53 gene mutation and MVD were investigated in men with prostate cancer. Sections from 103 radical prostatectomy cases were evaluated with immunohistochemistry to detect mutant p53 proteins. Quantitative MVD was performed on the cases exhibiting p53 positive staining and compared with negative fields of similar Gleason grade on the same histologic sections. Twenty of the 103 cases (19.4%) revealed positive p53 staining nuclei. In 19 of these 20 cases, the MVD in p53 positive areas was greater than corresponding control regions (overall P<0.0001). Extent of p53 abnormality, as well as MVD, correlated with pathologic stage. These data suggest that mutations of the p53 tumour suppressor gene may be associated with increased angiogenesis in CaP. In addition to providing staging and prognostic information, this relationship potentially has therapeutic implications.

Journal Article↗
PubMed1997

Day to day changes in free and total PSA: significance of biological variation.

In this study we evaluated the physiological variation of free and total prostate-specific antigen (PSA) levels to determine how the percent free/total PSA was affected. Twenty four patients had blood drawn for ten consecutive weekdays. The percent coefficient of variation (%CV) of biological variation was calculated. The results were log-normally distributed with geometric means of 12.0% CV, 7.3% CV, and 8.8% CV for free, total, and percent free/total PSA, respectively. When applied, the percent free/total, PSA would need to fluctuate by 31% to indicate that a significant change (critical difference, P<0.05) between two measurements had occurred. Biological variation of PSA measurements is substantial.

Journal Article↗
PubMed1997

The Prostate Cancer Intervention Versus Observation Trial (PIVOT).

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized trial designed to determine whether radical prostatectomy or expectant management provides superior length and quality of life for men with clinically localized prostate cancer. Conducted at Department of Veterans Affairs and National Cancer Institute medical centers, PIVOT will enroll over 1,000 individuals < 75 years of age. The primary study end point is all-cause mortality. Secondary outcomes include prostate cancer- and treatment-specific morbidity and mortality, health status, predictors of disease-specific outcomes, and cost-effectiveness. Within the first 3 years of enrollment, over 400 men have been randomized. Early analysis of participants' baseline characteristics indicate that enrollees are representative of men diagnosed with clinically localized prostate cancer throughout the United States. Therefore, results of PIVOT will be generalizable. These results are necessary in order to determine the preferred therapy for clinically localized prostate cancer.

Aged↗