Prostate Carcinoma Screening Research Articles

Histopathological screening for prostate carcinoma: is a benign biopsy a negative biopsy?

In case of clinical suspicion of a prostate malignancy, a prostate biopsy is the most widely used approach to confirm prostate cancer. Unfortunately, exclusion of prostate cancer is not feasible by means of biopsy and also the negative rate remains consistently high. Here, we review the information the surgical pathologist can still gain from a prostate biopsy in absence of overt carcinoma.

Carcinoma core distribution in patients with palpable and nonpalpable prostate tumors

Introduction of prostate‐specific antigen (PSA)–based screening for prostate carcinoma has led to a significant increase in the detection of prostate carcinoma. Prostate core needle biopsy remains the gold standard as a diagnostic tool with which to ascertain disease status. In this issue of Cancer, Demura et al. challenge some commonly accepted concepts regarding the zonal distribution of prostate carcinoma and explore the distribution of carcinoma cores within the prostate as well as the potential impact of a systematic, ultrasound‐guided transperineal template biopsy in improving carcinoma detection rates.

Screening for prostate carcinoma

To date, the use of prostate‐specific antigen (PSA) screening in the U.S. has translated into lower PSA failure rates and, perhaps, to lower rates of disease‐specific mortality in men with prostate carcinoma. However, this later point remains a hypothesis and will be proven right or wrong in short order based on upcoming results from randomized screening studies.See also pages 943–51.

Results of a Randomized, Population-Based Study of Biennial Screening Using Serum Prostate-Specific Antigen Measurement to Detect Prostate Carcinoma

BACKGROUND. The purpose of the current study was to evaluate the effectiveness of a prostate carcinoma screening program in which serum prostate-specific antigen (PSA) levels were measured. METHODS. From a group of 20,000 men born between January 1, 1930, and December 31, 1944, 10,000 men were randomized into a screening group and 10,000 were randomized into a control group. Patients in the screening group were invited to undergo initial PSA testing between 1995 and 1996 and then were invited to receive testing every second year thereafter for 8 years (for a total of 4 PSA tests). Men with PSA levels 3 ng/mL (or 2.54 ng/mL, in the third and fourth screening rounds) were invited to undergo clinical investigation, which included sextant biopsy of the prostate. By linking to the regional cancer registry, the authors were able to obtain the true and expected incidence rates for the screening and control groups. RESULTS. The screening participation rate was high (73%). A total of 884 malignancies have been detected to date, with 640 having been detected in the screening group. There was an early and marked shift toward more favorable disease stage and grade for malignancies detected on repeat screening. In the fourth screening round, only 2 of 82 detected malignancies were classified as advanced disease. Of the 227 screen-detected tumors on which surgery was performed, only 20 (8.8%) had small volume ( 0.2 cm). Forty-three interval malignancies were detected, but only five were accompanied by symptoms. At 8 years, the cumulative disease incidence rate among screening participants was 7.3%, compared with 2.4% in the control arm. The incidence rate observed in the screening population corresponds to the cumulative incidence rate observed in the Swedish male population at age 72 years. CONCLUSIONS. Biennial PSA screening was very successful in diagnosing prostate carcinoma at an early stage, when curative treatment typically is effective. In addition, the results regarding interval malignancies were favorable. Thus, decreased mortality should be observed on long-term follow-up. The lead time associated with screening appears to fall within the range described in earlier studies involving frozen sera (i.e., 5–9 years).

Spread of prostate carcinoma to the perirectal lymph node basin: analysis of 112 rectal resections over a 10-year span for primary rectal adenocarcinoma.

We recently identified metastatic prostate carcinoma (PCA) within perirectal lymph nodes (PLNs) from 2 patients undergoing abdominoperineal resection (APR) for rectal adenocarcinoma (RA). As this phenomenon has not been addressed by any studies in the literature and because these positive PLNs had the potential to be mistakenly diagnosed as metastatic RA, we were prompted to undertake a retrospective study of rectal resections for RA to determine the frequency of PCA metastasizing to the PLNs in this patient population. The laboratory information system of the Department of Pathology, Capital Health, Halifax, Nova Scotia was searched for lymph node (LN)-positive RAs resected by low anterior resection or APR in male patients between January 1, 1992 and December 31, 2002. The hematoxylin and eosin slides were retrieved and reviewed, comparing the histology of the primary rectal tumor with that of the LN metastases in each case. Metastases having a different histologic appearance than the primary rectal tumor or having a pattern suggestive of metastatic PCA were analyzed by immunohistochemistry to detect prostate specific antigen (PSA), prostatic acid phosphatase (PAP), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and carcinoembryonic antigen in LN metastases and in each RA. The presence or absence of mucin in the tumors was assessed by staining with Alcian blue, periodic acid-Schiff (PAS) +/- diastase, and modified PANFOPAS (2-hydroxy-3-naphthoic acid hydrazide/fast black B/saponification/periodic acid-Schiff). The study identified 112 cases of RA with positive LNs. Of those, 5 of 112 (4.5%) were identified as having metastatic PCA within the PLNs. All five were positive for PSA and PAP and only one case had rare CK20-positive tumor cells. The primary RAs were all diffusely positive for CK20 and carcinoembryonic antigen. Two cases of metastatic PCA expressed colonic type/acetylsialomucin, which was also seen in well-differentiated primary RAs. These 5 patients had a mean age of 76.8 years (range, 68-82 years). Four (80%) underwent APR while one (20%) underwent a low anterior resection. The mean number of LNs identified per case was 14 (range, 5-26). The mean number of LNs per case with metastatic PCA was 7.6 (range, 1-18). The majority of the LNs were under 1.0 cm in diameter. Two cases (40%) were associated with significant extranodal extension of PCA. The PLNs were mistakenly diagnosed as being involved by RA 40% of the time. On follow-up, 2 patients (40%) had died with progressive pelvic tumor, while 3 patients (60%) were alive, including 2 who, as a result of the study, were referred to the urology service for management. Both of these patients were subsequently started on medical (anti-androgen) therapy and 1 additionally had bilateral orchiectomy. In 4 of the patients, the serum PSA after the rectal resection ranged from 2.5 to 13.5 ng/mL. In 1 patient, the serum PSA was markedly elevated (5961 ng/mL), and this patient was subsequently identified on bone scan as having extensive skeletal metastases. This study identified a subset (4.5%) of patients with RA and PLNs positive for PCA. PCA may extend to the PLN basin and therefore influence the management of patients with rectal tumors and the staging, LN dissection, and management of patients with PCA. Moreover, the LNs were incorrectly diagnosed as metastatic RA 40% of the time, emphasizing the need to consider the differential diagnosis of metastatic PCA when evaluating PLNs. The diagnosis of metastatic PCA can be confirmed using an immunohistochemical panel consisting of PSA, PAP, CK20, and carcinoembryonic antigen along with mucin stains in some cases. In patients undergoing APR for RA, there should be preoperative screening for PCA as it will not be possible to do a digital rectal examination or transrectal ultrasound post-APR, and a prostate biopsy, if necessary, would have to be done via the more difficult transperineal approach.

Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker.

The widespread use of prostate-specific antigen (PSA) screening has had a tremendous impact on all aspects of the management of prostate carcinoma. Although PSA-based screening has resulted in a stage migration to more organ-confined tumors at the time of diagnosis, and has been temporally associated with a decrease in prostate carcinoma mortality, PSA screening is imperfect. A recent analysis of results from the Prostate Cancer Prevention Trial (PCPT) has provided insight into the positive predictive value of PSA in the so-called "normal" range. The history of the discovery, initial studies, and subsequent widespread application of PSA screening is reviewed. The application of PSA for screening preceded the development of current prostate biopsy techniques and an upper limit of normal was established without complete disease ascertainment. More recent modifications of PSA-based screening have been adopted clinically without sufficient validation. With current methods, overdiagnosis of clinically unimportant disease almost certainly occurs and high-grade, aggressive disease may not be detected sufficiently early to allow successful treatment. To the authors' knowledge, the optimal upper limit of normal for PSA for prostate carcinoma screening is unknown. New biomarkers of disease are needed; these must be linked with disease prognosis and must be validated in rigorously designed clinical trials.

Survellaince Program for Prostate Carcinoma: Preliminary Results on 585 Blood Donors

Population screening for prostatic carcinoma (CP) is a struggled subject, and we don't know the real utility of it. Nowadays the Authors suggest only survey on little groups. In this study the male population of blood donors of our hospital between 45 and 65 years underwent a complete valutation for CP. From this study we hope to obtain the following results: a) early diagnosis of CP (eradicable); b) eliminate keeper of neoplastic pathology from blood donations (theoretic risk of transmission of neoplastic cells in immunodepressed patients); c) studying the practicability, if we achieve a high percentage of ahdesions at this program, our model could be exportable.

Prostate carcinoma among men with human immunodeficiency virus infection.

Several malignancies are known to occur more frequently in individuals with human immunodeficiency virus (HIV) infection. To determine the incidence of prostate carcinoma in men with HIV infection, the authors initiated a prostate carcinoma screening program in a large HIV clinic. Beginning in February 2002, monitoring of prostate-specific antigen (PSA) levels and digital rectal examination (DRE) were included in the routine annual health maintenance provided to men with HIV infection age > or = 35 years who were followed in the infectious disease clinic at the Naval Medical Center San Diego. All men with prostate carcinoma in this population over the last 2 years were reviewed. Demographic data (age, ethnicity), duration of HIV infection, laboratory values (CD4 counts and HIV viral load), and medication use were determined by medical record review. Men with elevated PSA levels (levels above age-adjusted PSA values or PSA velocity > or = 0.75 ng/mL per year) or abnormal DRE results were referred for urologic evaluation. Comparisons between groups were performed using a logistic regression model and the Fisher exact test. Multivariate analysis was performed by logistic regression to determine relations between prostate carcinoma and patient characteristics. Two hundred sixty-nine men age > or = 35 years (mean age, 43.4 years; range, 35-72years) underwent prostate carcinoma screening by DRE, and 216 men also received PSA testing. Overall, 56.3% of the patients were white, 28.7% were African American, and 15% were of other racial ethnicity. Of the 216 men, 7 (3.2%) had elevated PSA values, and none had abnormal DRE results. Three patients were diagnosed with prostatitis (PSA range, 3.3-25.7 ng/mL), and 1 patient had high-grade prostatic intraepithelial neoplasia, which was determined after a biopsy was performed. Repeat PSA evaluations were within normal limits for the remaining three patients. Review of the cohort during the 2-year period before the current study was initiated revealed 5 additional cases of prostate neoplasia. Prostate carcinoma was common (4 of 11 men, 36.4%) in men age > 60 years and occurred with relatively preserved CD4 counts (mean, 509 cells/mm(3)). In multivariate analysis, African-American race (P = 0.020) and duration of HIV infection (P = 0.047) were found to be associated with the development of prostate carcinoma. Prostate carcinoma screening identified abnormal PSA values in 3.2% of the HIV-positive cohort, many associated with prostatitis. Prostate carcinoma was common in older men and was associated with duration of HIV infection. As the life expectancy of men with HIV infection increases, prostate carcinoma screening will become increasingly important in this population.

A neurocomputational model for prostate carcinoma detection.

Current guidelines for prostate carcinoma screening rely primarily on the digital rectal examination (DRE) and prostate specific antigen (PSA). Well described patient risk factors for prostate carcinoma also include age, ethnicity, family history, and complexed PSA. However, due to the nonlinear relation of each of these variables with prostate carcinoma, it is difficult to predict reliably each patient's risk based on linear univariate analysis. The authors investigated a neural network to model the risk of prostate carcinoma by seven readily available clinical features. The database for the current study comprised 3268 men recently evaluated for the early detection of prostate carcinoma. The seven clinical features evaluated included age, race, family history, International Prostate Symptom Score (IPSS), DRE, and total and complexed PSA. Three hundred forty-eight subjects in the dataset included men with determined prostate biopsy outcomes and for whom at least 6 of 7 features were available. The dataset was divided randomly into a training set (60%) and a test set (40%), with n1/n2 cross-validation used to evaluate model accuracy, and was modeled with linear and quadratic discriminant function analysis and a neural computational system. After a model with acceptable goodness of fit was achieved, reverse regression analysis using Wilks's generalized likelihood ratio test was performed to evaluate the statistical significance of each input variable. The receiving operating characteristic (ROC) area for the neural computational system in the test set was 0.825, whereas total PSA and complexed PSA alone had ROC areas of 0.678 and 0.697, respectively. The ROC area of logistic regression in the test set was 0.510, linear discriminant function analysis was 0.674, and quadratic discriminant function analysis was 0.011. All were significantly less than the ROC area of the neural computational model (all Ps < 0.002). Reverse regression based on Wilks's generalized likelihood ratio test demonstrated each input feature to be highly significant to the model (all Ps << 0.000001). The authors modeled a combination of well described patient risk factors for prostate carcinoma using a neural computational system with acceptable goodness of fit. They demonstrated that each of the seven variates on which the model was based was critically significant to model performance. The authors presented this model for clinical use and suggested that clinicians use it in deciding to perform prostate biopsy.

Pathology of Tumours of the Male Genital Tract

Tumours of the male genital tract are common and are increasing in frequency, particularly in the ‘Western’ world. The most common tumours are those of the testis and prostate, although penile and urethral tumours are occasionally encountered. Testicular and prostatic tumours occur in different age groups. Testicular tumours are the most common malignant solid tumour in young men in their third and fourth decade. Prostate cancer is the most common tumour in older men and, in England and Wales, is the second most common malignant cause of death after lung cancer. There have been significant advances in the diagnosis of both of these tumour types, and in understanding their pathology, particularly of the preneoplastic phase. The high incidence of prostatic carcinoma and its increasing morbidity and mortality have led to calls for the development of a prostate cancer screening programme. A combination of digital rectal examination and serum prostate-specific antigen (PSA) analysis is effective in diagnosis with subsequent transrectal ultrasound-guided needle biopsy. However, there is significant sampling error entailed in these procedures with a risk of false-negative screening data. It is also remains debatable whether a small, early lesion detected by a screening programme would show any benefit from therapeutic intervention at this stage. Pilot studies of prostate carcinoma screening are under way in a variety of countries, but there are no data of the efficacy of these programmes.

Impact of undergoing prostate carcinoma screening on prostate carcinoma-related knowledge and distress.

Despite the ongoing controversy regarding the utility of prostate carcinoma (PCa) screening, the prevalence of asymptomatic men who participate in free PCa screening programs is on the rise. However, this increased awareness has not been associated with increased knowledge about the potential limitations of PCa creening. We conducted a prospective assessment to delineate men's motivations for undergoing screening and to determine the impact of screening on psychological distress and on men's knowledge about PCa screening. We conducted two telephone interviews with a group of 136 men registered to undergo free PCa screening at two hospital-based sites. The first interview was conducted before screening and the second interview followed receipt of the screening results. Interviews assessed demographics and screening history, reasons for undergoing the current screening, cancer-related and general psychological distress, knowledge of risk factors for PCa, and knowledge of the benefits and limitations of screening. Only participants with normal screening results were included in these analyses. "Seeking peace of mind about prostate cancer" was rated as the most important reason for undergoing screening. PCa-related distress decreased following receipt of a negative result (P < 0.01). Stratified analyses indicated that this was particularly true among younger men and African American men (both Ps < 0.001). Awareness of the benefits of screening was very high, but awareness of limitations was low, with fewer limitations reported following screening compared with prescreening (P < 0.01). Although awareness of the established risk factors improved following screening, controversial risk factors (i.e., those with limited empirical support) and factors that were unrelated to PCa risk were also rated as more important in the development of PCa than they were before screening (all Ps < 0.05). Therefore, the results may reflect that following screening, participants were simply more likely to endorse plausible risk factors, rather than actually reflecting an increase in participants' knowledge. These results suggest the importance of developing informed consent procedures and educational programs for the asymptomatic men who participate in free prostate screening programs each year, as the decision to be screened is being made without the benefit of a full understanding of the current state of medical knowledge about PCa screening. Until the definitive results of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial are available, improved patient education is needed to assist men in making screening decisions consistent with their own preferences.

Radioiodination of monoclonal antibody for prostate specific antigen

Prostate specific antigen (PSA) is a reliable biochemical marker used in screening for prostate carcinoma. Immunoradiometric assays (IRMA) are generally used for the estimation of total/free PSA in serum samples. Radiolabeled antibody, an important reagent of IRMA was prepared and characterized using an in-house anti-PSA monoclonal antibody (Mab), Mab-2S. Mab-2S was radiolabeled with 125I and characterized for immunoreactivity and radiochemical purity. The usability of the radioiodinated Mab as tracer in IRMA was ascertained using authentic reagents for IRMA of PSA.

PROSTATE CANCER DIAGNOSIS USING A SATURATION NEEDLE BIOPSY TECHNIQUE AFTER PREVIOUS NEGATIVE SEXTANT BIOPSIES

We hypothesized that markedly increasing the number of cores obtained during prostate needle biopsy may improve the cancer detection rate in men with persistent indications for repeat biopsy. We performed saturation ultrasound guided transrectal prostate needle biopsy in 224 men under anesthesia in an outpatient surgical setting in whom previous negative biopsies had been performed in the office. The mean number of previous sextant biopsy sessions plus or minus standard deviation before saturation biopsy was 1.8 (range 1 to 7). A mean of 23 saturation biopsy cores (range 14 to 45) were distributed throughout the whole prostate, including the peripheral, medial and anterior regions. Indications for repeat biopsy were persistent elevated serum prostate specific antigen (PSA) in 108 cases, persistent elevated PSA and abnormal rectal examination in 27, persistent abnormal rectal examination in 4, high grade prostatic intraepithelial neoplasia in the previous biopsy in 64 and atypia in the previous biopsy in 21. Cancer was detected in 77 of 224 patients (34%). The number of previous negative sextant biopsies was not predictive of subsequent cancer detection by saturation biopsy. Median PSA was 8.7 ng./ml. and median PSA velocity was 0.63 ng./ml. yearly. Of the 77 patients in whom cancer was detected radical prostatectomy was performed in 52. Pathological stage was pT2 in 48 patients and pT3 in 4, while Gleason score was 4 to 5, 6 to 7 and 8 in 5, 46 and 1, respectively. At prostatectomy median cancer volume was 1.04 cc and 85.7% of removed tumors were clinically significant, assuming a 3-year doubling time. The overall complication rate for saturation needle biopsy was 12% and hematuria requiring hospital admission was the most common event. Saturation needle biopsy of the prostate is a useful diagnostic technique in men at risk for prostate cancer with previous negative office biopsies. This technique allows adequate sampling of the whole prostate gland and has a detection rate of 34% in this cohort of patients.

Long term follow‐up of mass screening for prostate carcinoma in men with initial prostate specific antigen levels of 4.0 ng/ml or less

BACKGROUND Long term follow-up for subjects whose initial prostate specific antigen (PSA) levels were 4.0 ng/mL or lower was conducted to investigate the proper interval for PSA screening. METHODS Eight thousand five hundred ninety-five men aged 50 years or older with an initial PSA level of 4.0 ng/mL or lower were screened with tumor marker measurement and/or digital rectal examination (DRE) and/or transrectal ultrasonography as a first step in the mass screening, and a prostate biopsy was performed for individuals with abnormal findings. RESULTS Cancer was detected in 0.18% (8 of 4526), 1.0% (27 of 2724), and 3.6% (49 of 1345) of men whose initial PSA levels were lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. Among these prostate carcinoma cases, 25% (6 of 8), 56% (15 of 27), and 63% (31 of 49) were detected by abnormal PSA in patients with initial PSA levels lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. The detection rates of prostate carcinoma within 3 years after the initial visit were 0.07%, 0.24%, and 1.2% in cases with initial PSA levels lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. CONCLUSIONS It is recommended that DRE and PSA measurements should be performed once every 3 years in individuals with initial PSA levels of less than 1.0 ng/mL. The prostate carcinoma detection rate increased over time in individuals with initial PSA levels of 1.0 to 4.0 ng/mL, especially in cases with 2.0–4.0 ng/mL, and annual measurement of PSA was more useful than DRE. Therefore, it is recommended that PSA screening should be performed once every year for individuals with initial PSA levels of 1.0 to 4.0 ng/mL. Cancer 2001;91:744–51. © 2001 American Cancer Society.

Prostate carcinoma knowledge, attitudes, and screening behavior among African-American men in Central Harlem, New York City.

Although the benefits of prostate carcinoma screening in reducing mortality rates have not been proven or shown to be cost-effective, screening, particularly using prostate specific antigen (PSA) tests, is widespread. A better understanding of screening behavior, knowledge of prostate carcinoma risk, and attitudes toward screening among men at high risk, such as African-American men, would be valuable. A prevalence survey was conducted using 2 samples of African-American men, aged 50-74 years: a clinic sample drawn from all clinics in Central Harlem (n = 404) and a random-digit dial sample from the same geographic region (n = 319). The prevalence of self-reported PSA screening was estimated using a cognitive survey methodology based on the internal consistency of answers to four different questions. Prevalence estimates were adjusted to take into account the high proportion of nontelephone residences. The clinic sample, representing a poorer, more ill population (as determined by MOS Physical Function Scores, was less likely to report PSA screening than the community sample (11.1% in clinic sample vs. 25.5% in community). The prevalence of PSA testing in Central Harlem overall in this age group by using two different techniques was estimated to be 24%. In multiple logistic models, self-reported PSA screening was associated with age, education, favorable attitudes toward screening, and knowing someone who had prostate carcinoma. However, the association between these factors and the likelihood of self-reported PSA screening differed between clinic and community samples. The prevalence of self-reported PSA screening in Central Harlem was lower than that reported for other populations. These findings may be useful in the design of health education campaigns and for counseling innercity, low-income African-American patients appropriately about the disease.

Long term follow-up of mass screening for prostate carcinoma in men with initial prostate specific antigen levels of 4.0 ng/ml or less

Long term follow-up for subjects whose initial prostate specific antigen (PSA) levels were 4.0 ng/mL or lower was conducted to investigate the proper interval for PSA screening. Eight thousand five hundred ninety-five men aged 50 years or older with an initial PSA level of 4.0 ng/mL or lower were screened with tumor marker measurement and/or digital rectal examination (DRE) and/or transrectal ultrasonography as a first step in the mass screening, and a prostate biopsy was performed for individuals with abnormal findings. Cancer was detected in 0.18% (8 of 4526), 1.0% (27 of 2724), and 3.6% (49 of 1345) of men whose initial PSA levels were lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. Among these prostate carcinoma cases, 25% (6 of 8), 56% (15 of 27), and 63% (31 of 49) were detected by abnormal PSA in patients with initial PSA levels lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. The detection rates of prostate carcinoma within 3 years after the initial visit were 0.07%, 0.24%, and 1.2% in cases with initial PSA levels lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. It is recommended that DRE and PSA measurements should be performed once every 3 years in individuals with initial PSA levels of less than 1.0 ng/mL. The prostate carcinoma detection rate increased over time in individuals with initial PSA levels of 1.0 to 4.0 ng/mL, especially in cases with 2.0-4.0 ng/mL, and annual measurement of PSA was more useful than DRE. Therefore, it is recommended that PSA screening should be performed once every year for individuals with initial PSA levels of 1.0 to 4.0 ng/mL.

Intraindividual variation of prostate specific antigen measurement and implications for early detection of prostate carcinoma.

Many researchers have described intraindividual prostate specific antigen (PSA) variation, but its implications for a prostate carcinoma screening program have not been well appreciated. In this study, the author explored misclassification problems associated with intraindividual PSA variation. The previous research work on intraindividual PSA variation was reviewed and summarized. Then, on the basis of the results from the previous work and a simple measurement error model, the author estimated misclassification probabilities for a single PSA measurement. With a variance-based approach of meta-analysis, the author derived a summary coefficient of variation (13.1%) of the intraindividual PSA variation from the previous relevant studies. They found that there were substantial risks for misclassification, especially among those with PSA values near the recommended cutoff point (4.0 ng/mL). For an individual with a true PSA level at 3.9 ng/mL, the risk for misclassification as PSA higher than 4.0 ng/mL was approximately 42%; for an individual with a true PSA value at 3.0 ng/mL, the risk was less than 1%. Intraindividual PSA variation should become a part of interpreting PSA test results, especially for men with a PSA value near the cutoff point. Both sensitivity and specificity of PSA test reported in the literature have been underestimated, and the risk of prostate carcinoma associated with PSA test results has been biased down to the null (no effect) because of the intraindividual PSA variation.

RADICAL PROSTATECTOMY: THE VALUE OF PREOPERATIVE, INDIVIDUALLY LABELED APICAL BIOPSIES

RADICAL PROSTATECTOMY: THE VALUE OF PREOPERATIVE, INDIVIDUALLY LABELED APICAL BIOPSIES

RETRACTED: Prostate cancer screening in the Tyrol, Austria: experience and results

This article summarises the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) and per cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95 were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA levels and prostate carcinoma was detected in 62 men (3%). All patients underwent radical prostatectomy and histological examination revealed organ-confined tumour in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of these patients (29%) had carcinoma that originated in the transition zone only. In the retrospective study, receiver operating characteristic curve analysis showed that by using a per cent free PSA of less than 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106/158 men (67%) with elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate carcinomas were detected. By using a per cent free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120/465 men (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free PSA<18% were further evaluated and 27 (23%) were found to have prostate carcinomas. Receiver operating characteristic curve analysis for PSA transition zone (TZ) density showed that by using a PSA transition zone density of >22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3 carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. The rate of organ-confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this evaluation a new approach, to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cut-off point was developed. High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. In this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. The results of this evaluation suggest that older men have larger tumour volumes compared with younger men with the same PSA levels. These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.

A prospective study of the serum prostate specific antigen concentrations and gleason histologic scores of black and white men with prostate carcinoma

The stage specific survival rates of black American men with prostate carcinoma are less favorable than those of white American men. The authors conducted a prospective study of the serum prostate specific antigen (PSA) concentrations and Gleason histologic scores of black and white men with newly diagnosed prostate carcinoma to determine whether there were racial differences in these prognostic variables. At a Veterans Affairs Medical Center between January 1, 1992, and December 31, 1997, clinical stage, Gleason histologic score, serum PSA concentration, prostate volume, and PSA density were determined for 796 consecutive men (465 black and 331 white) who had biopsy-detected prostate carcinoma. The percentages, respectively, of black and white men with local, regional, and metastatic carcinoma were 58 and 72; 22 and 17; and 20 and 11 (P < 0.0001). Of 271 black and 329 white men with local stage cancer, 20% and 12%, respectively, had Gleason 8-10 tumors (P = 0.02), and the age-adjusted risk of Gleason 8-10 cancer was 1.39 times greater for black men (95% confidence interval [CI] = 1.09-2.93). Gleason 8-10 cancer was found in 12 of 68 black (18%) and 5 of 87 white (6%) men with local cancer who were age 65 years or younger (P = 0.02). Among black and white men with local stage cancer, the mean PSA was 12.9 (95% CI = 11.5-14.4) and 8.5 (95% CI = 7.6-9.4) ng/mL, respectively (P < 0.0001), and among black and white men with regional stage cancer the mean PSA was 53.3 (95% CI = 42.7-63.9) and 35.0 (95% CI = 27.3-42.6) ng/mL, respectively (P = 0.02). The mean PSA of black and white men with local cancer who were age 65 years or younger was 11.6 (95% CI = 8.8-14.4) and 6.9 (95% CI = 5.9-8.0) ng/mL, respectively (P = 0.0009). Disparities in the risk of Gleason score 8-10 cancer for black and white men with local stage disease and in the serum PSA concentrations of black and white men with local and regional stage disease help to explain racial differences in cancer survival. Racial differences in the risk of Gleason 8-10 cancer and in the serum PSA concentrations of men age 65 years or younger have implications regarding the potential benefits of screening for prostate carcinoma in the African American community.