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Background: The utility of digital rectal examination (DRE) as a screening test for early detection of prostate cancer has not been established. Therefore, we evaluated the usefulness of DRE as a stand-alone screening test and in conjunction with measured serum prostate-specific antigen (PSA) levels of 0-3.9 ng/mL and transrectal ultrasonography (TRUS).Methods: Our study population consisted of 10,523 men aged 54-76 years who were randomly assigned to the screening arm of the Rotterdam, The Netherlands, section of the European Randomized Study of Screening for Prostate Cancer. The underlying prevalence of detectable prostate cancer was estimated by logistic regression analysis and used for calculating the sensitivity of DRE as a test. Pathologic characteristics of 105 radical prostatectomy specimens were used to determine the aggressiveness of the tumors diagnosed (and missed) by DRE.Results: The overall detection rate for prostate cancer in this population when serum PSA measurement, DRE, and TRUS were used was 4.5%, and the detection rate with DRE alone was 2.5%. The positive predictive value of DRE ranged from 4% to 11% in men with PSA levels of 0-2.9 ng/mL and from 33% to 83% in men with PSA levels of 3.0-9.9 ng/mL or more. Most tumors detected by DRE in men with PSA levels of less than 4.0 ng/mL were small (mean volumes = 0.24-0.83 mL), and most were well differentiated (Gleason scores of 6 or less). Minimal, moderate, and advanced cancers were seen in 42%, 42%, and 16% of men, respectively, with a PSA level of 4.0 ng/mL or less. DRE alone allowed detection of 264 (55.8%) of 473 cancers; 82 (17.3%) of the 473 cancers would have remained undetected by PSA-based screening alone (i.e., no follow-up procedures for PSA values of 0-3.9 ng/mL).Conclusions: For PSA values of 0-3.9 ng/mL, the positive predictive value and sensitivity of DRE, tumor volume, and tumor grade were strongly dependent on PSA level. DRE has a poor performance in low PSA ranges. [ABSTRACT FROM AUTHOR]

To assess the consistency of grading outcome among seven of eight participating centres of the European Randomised Screening Program of Prostate Cancer (ERSPC), a multicentre randomized trial intended to detect a difference in prostate cancer-related mortality between screened participants and a control group. Currently, tumour stage and grade in prostatectomy specimens represent the most predictive variables for biological behaviour. In prostate needle biopsies the tumour grade is a strong factor for deciding therapy. Within the ERSPC all prostate cancers detected in needle biopsies were graded according to the Gleason score system. Gleason scores were compressed in three categories of ≤ 6, 7 and 8–10. Data for grading outcome were obtained from the databases from seven individual centres; in one centre the slide sets with cancer were separately reviewed. Combining the data of seven ERSPC centres 66% of cancers detected in the screening arm were Gleason score ≤ 6 and 92% were ≤7. Gleason score 8–10 cancers varied from 2 to 11%. This variation in Gleason scores may be attributed to differences in the population characteristics and biopsy indications. These data indicate that in the seven ERSPC centres most screen-detected cancers have favourable characteristics on biopsy. Men with these cancers are amenable for treatment with curative intent. The observed differences in Gleason score distribution in different centres may partly be attributed to geographical differences and differences in the age range of the screened populations. [ABSTRACT FROM AUTHOR]

The Grade group is an important parameter for clinical decision-making in prostate cancer. Recently, percent Gleason pattern 4 and presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) have been recognized for their independent predictive value for prostate cancer outcome. There is sparse data on the inter-observer agreement for these pathologic features in practice. Our objectives were to investigate inter-observer variability of percent Gleason pattern and CR/IDC and to relate individual tumour scores to clinical outcome. Our cohort included 80 consecutive radical prostatectomies with a median follow-up 87.1 months (interquartile range 43.3-119.2), of which the slide with largest tumour volume was scored by six pathologists for Grade group (four tiers: 1, 2, 3 and 4/5), percent Gleason pattern 4 (four tiers: 0-25%, 26-50%, 51-75% and 76-100%) and presence of CR/IDC (two tiers: absent, present). The individual assignments were related to post-operative biochemical recurrence (20/80). Inter-observer agreement was substantial (Krippendorff's α 0.626) for assessment of Grade group and moderate for CR/IDC (α 0.507) and percent Gleason pattern 4 (α 0.551). For each individual pathologist, biochemical recurrence rates incremented by Grade group and presence of CR/IDC, although such relation was less clear for percent Gleason pattern 4. In conclusion, inter-observer agreement for CR/IDC and percent Gleason pattern 4 is lower than for Grade groups, indicating awareness of these features needs further improvement. Grade group and CR/IDC, but not percent Gleason pattern 4 was related to biochemical recurrence for each pathologist, indicating overall validity of individual grade assignments despite inter-observer variability.

Screening for prostate cancer using prostate-specific antigen (PSA) tests has led to a stage and grade shift as compared to the pre-PSA era. Effectiveness of screening for prostate cancer should be manifested by a reduction in detection rate of aggressive cancers during subsequent screening. In 6 centers of the European Randomized Screening study for Prostate Cancer, a total of 58,710 men were tested for prostate cancer. Screening centers differed with regard to age-range, screening interval and biopsy indications. During the 2nd visit, the proportion of Gleason score 6 cancers increased from 62.5 to 75%, mainly at the expense of Gleason score 7 cancers. High-grade (Gleason score 8-10) cancer detection rates varied per screening center during the 1st visit from 5.1 to 41.1, and during the 2nd visit from 6.4 to 29.3/10,000 men. The overall detection rate of high-grade cancers showed a reduction during the 2nd visit from 26 to 12/10,000 men, an effect mainly attributable to the screening center with the highest cancer detection rate (i.e. 507/10,000 men). Variations in detection rates among screening centers related among others to biopsy compliance and age range., (Copyright (c) 2005 Wiley-Liss, Inc.)

Introduction: Prostate-specific antigen (PSA) testing of asymptomatic men may lead to the detection of "minimal" prostate cancers that are less likely to be associated with morbidity or mortality., Objective: To examine the significance of various diagnostic outcomes from needle biopsies of the prostate in an asymptomatic population of men., Methods: Prostatic needle biopsy findings were matched with those from radical prostatectomy specimens using data from the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC). Men, aged between 55 and 75 years, with elevated PSA levels underwent lateralized sextant needle biopsies. In corresponding radical prostatectomy specimens, the tumor categories (minimal, moderate, or advanced) were determined., Results: Prostate cancer was diagnosed in 5.1% of 19,970 screened men, and 31.6 % of the men had cancers that were categorized as "minimal." Repeat biopsies performed after initial diagnoses of either isolated prostatic intra-epithelial neoplasia (PIN) or "suspicious for malignancy," detected adenocarcinoma in 12.1%and 36.5 % of the men, respectively. In a substudy of 510 men with a benign biopsy outcome 12 months previously, repeat biopsies detected adenocarcinoma in 12.4 of the men. Of men who were subsequently treated with radical prostatectomy, the cancers were classified as "minimal" in 27.8% of the men with previously benign biopsies and in 47.4% of the men with previously suspicious lesions,, Conclusions: The chance of finding a "minimal" prostate cancer in an asymptomatic population is substantial and increases when a repeat biopsy is performed following a biopsy with a suspicious outcome.

Since the introduction of serum testing for prostate-specific antigen (PSA) in 1990 for the early detection of prostate cancer, the number of men undergoing a prostate needle-biopsy procedure has increased dramatically. In order to highlight the significance of the various diagnostic outcomes of a prostate needle biopsy, the pathological findings from needle biopsies were compared with those from samples taken during radical prostatectomy and in follow-up biopsies, using data from the 'European randomised screening for prostate cancer' (ERSPC) trial. In men with an elevated PSA value and a benign or negative needle-biopsy result, 10-15% were found to have prostate cancer in follow-up biopsies. In men with a needle-biopsy diagnosis of adenocarcinoma, 29% were found to have questionable histopathological characteristics or minimal cancer that did not require therapy. The incidence of minimal cancer increased to 70% among men with a needle-biopsy diagnosis of focal carcinoma, i.e. a small focus (< 3 mm diameter) of well-differentiated adenocarcinoma, based on one biopsy from a series of six. In men with a needle-biopsy diagnosis of 'suspected malignancy' 36.5% were found to have prostate cancer in follow-up biopsies. In men with a needle-biopsy diagnosis of 'high grade prostatic intra-epithelial neoplasia' 13% were found to have prostate cancer in follow-up biopsies. This percentage was not significantly higher than the percentage of cancers detected after an initially benign biopsy outcome. To avoid over-treatment of a substantial number of men who lack symptoms of prostate cancer but are diagnosed on the basis of biopsy results, it is vital that clinical/pathologic parameters are developed and validated that can help in deciding whether to initiate curative treatment immediately.

Background: The currently recommended frequency for prostate-specific antigen (PSA) screening tests for prostate cancer is 1 year, but the optimal screening interval is not known. Our goal was to determine if a longer interval would compromise the detection of curable prostate cancer., Methods: A cohort of 4491 men aged 55-75 years, all participants in the Rotterdam section of the European Randomized Study of (population-based) Screening for Prostate Cancer, were invited to participate in an initial PSA screening. Men who received that screening were invited for a second screen 4 years later. Pathology findings from needle biopsy cores were compared for men in both rounds. Statistical tests were two-sided., Results: A total of 4133 men were screened in the first round (the prevalence screen), and 2385 were screened in the second round. The median amount of cancer in needle biopsy sets was 7.0 mm (95% confidence interval [CI] = 5.4 mm to 8.6 mm) in the first round and 4.1 mm (95% CI = 2.6 mm to 5.6 mm) in the second round (P =.001). Thirty-six percent of the adenocarcinomas detected in the first round but only 16% of those detected in the second round had a Gleason score of 7 or higher (mean difference = 20% [95% CI = 10% to 30%]; P<.001). Whereas 25% of the adenocarcinomas detected in the first round had adverse prognostic features, only 6% of those detected in the second round did (mean difference = 19% [95% CI = 11% to 26%]; P<.001). Baseline PSA values were predictive for the amount of tumor in biopsies in men with cancer in the first round but not for that in the second round., Conclusion: Most large prostate cancers with high serum PSA levels were effectively detected in a prevalence screen. In this population, a screening interval of 4 years appears to be short enough to constrain the development of large tumors, although it is inconclusive whether this will result in a survival benefit.

Background: The value of rectal examination as initial screening test for prostate cancer at low PSA values (0.0-3.9 ng/ml) was determined by evaluating the number and tumor characteristics of the cancers detected., Methods: Two study populations were subjected to screening with (n = 10,226) and without (n = 10,753) rectal examination as initial screening test. The number of cancers detected at low PSA values for both screening regimens, the corresponding biopsy and radical prostatectomy tumor characteristics were assessed. Possibly harmless cancers were defined as small (< 0.5 ml) organ-confined tumors without Gleason growth-patterns 4/5., Results: At low PSA, 26.6% (117/440) of screen-detected cancers were detected after the evaluation of a suspicious rectal examination. The number of cancers and tumor aggressiveness features were highly associated with serum-PSA level. The proportion of possibly harmless disease steadily declined from 100% (PSA 0.0-0.9 ng/ml) to 15.4% (PSA 3.0-3.9 ng/ml). Rectal examinations were performed unnecessarily in 94.7-100% of cases, when detection of clinically significant disease was aimed at. Using PSA (and a cut-off of 3.0 ng/ml) as the only screening tool, 24.3% (121/498) of screen-detected cancers were in the PSA range 3.0-3.9 ng/ml, and 60.0% were assessed as clinically significant., Conclusions: Rectal examination as initial screening test for prostate cancer at low PSA values may be replaced by screening using serum-PSA only. At PSA levels below 3.0 ng/ml, 289 rectal examinations are required to find one case of clinically significant disease, and 96 rectal examinations are needed to diagnose prostate cancer of any size, grade, or stage., (Copyright 2001 Wiley-Liss, Inc.)

No objective parameters have been found so far that can predict the biological behavior of early stages of prostatic cancer, which are encountered frequently nowadays due to surveillance and screening programs. We have applied comparative genomic hybridization to routinely processed, paraffin-embedded radical prostatectomy specimens derived from patients who participated in the European Randomized Study of Screening for Prostate Cancer. We defined a panel consisting of 36 early cancer specimens: 13 small (total tumor volume (Tv) < 0.5 ml) carcinomas and 23 intermediate (Tv between 0.5-1.0 ml) tumors. These samples were compared with a set of 16 locally advanced, large (Tv > 2.0 ml) tumor samples, not derived from the European Randomized Study of Screening for Prostate Cancer. Chromosome arms that frequently (ie, > or = 15%) showed loss in the small tumors included 13q (31%), 6q (23%), and Y (15%), whereas frequent (ie, > or = 15%) gain was seen of 20q (15%). In the intermediate cancers, loss was detected of 8p (35%), 16q (30%), 5q (26%), Y (22%), 6q, and 18q (both 17%). No consistent gains were found in this group. In the large tumors, loss was seen of 13q (69%), 8p (50%), 5q, 6q (both 31%), and Y (15%). Gains were observed of 8q (37%), 3q (25%), 7p, 7q, 9q, and Xq (all 19%). Comparison of these early, localized tumors with large adenocarcinomas showed a significant increase in the number of aberrant chromosomes per case (Rs = 0.36, P = 0.009). The same was true for the number of lost or gained chromosomes per case (Rs = 0.27, P: = 0.05; Rs = 0.48, respectively; P < 0.001). Interestingly, chromosomal alterations that were found in previous studies to be potential biomarkers for tumor aggressiveness, ie, gain of 7pq and/or 8q, were already distinguished in the small and intermediate cancers. In conclusion, our data show that chromosomal losses, more specifically of 6q and 13q, are early events in prostatic tumorigenesis, whereas chromosomal gains, especially of 8q, appear to be late events in prostatic tumor development. Finally, early localized tumors, as detected by screening programs, harbor cancers with aggressive genetic characteristics.

Background: Subdividing cancers according to the natural course of disease, both at the time of diagnosis and after radical prostatectomy, may influence management decisions of patients with prostate cancer. We investigated whether categorization of prostate cancers into different prognostic subgroups is feasible., Methods: In 218 screened participants of a randomized study, conventional post-operative tumor features were assessed for their accuracy in predicting PSA relapse after radical prostatectomy using Cox regression analysis. Independent prognostic tumor features were combined to identify subsets of cancers with similar biological potential. A cancer was defined that may be curable after its detection by screening tests, though is destined to progress to clinically manifest disease and cancer-related mortality in the absence of screening., Results: After a median follow-up of 33.0 months, pathological stage (P = 0.03), tumor volume (P = 0.04), and margin status (P = 0.01) each independently predicted PSA relapse after surgery. The proportion of poorly differentiated cancer proved highly superior to the Gleason score and most strongly predicted PSA relapse (P < 0.0001). Based on combined independent prognostic tumor features, a tumor classification model powerfully predicted PSA relapse., Conclusions: Based on tumor characteristics, possibly harmless, and conversely, possibly non-curable disease, may be distinguished from cancers that are likely to show clinical progression in the absence of screening and treatment. Prediction of these subclasses prior to treatment may eventually lead to proper patient management., (Copyright 2001 Wiley-Liss, Inc.)

Determining tumor stage provides a systematic way to describe the amount and the extent of a tumor at a certain point in time. In this short overview, the current version of the TNM system for prostate cancer is discussed. The TNM (tumor, lymph node, and metastasis) system is now used worldwide for determining tumor stage for prostate cancer. Tumor stage is essentially determined in two situations, at clinical evaluation of the patient (clinical stage) and after treatment by surgical removal of the prostate (pathological stage). In the ideal situation, clinical stage would be a reliable predictor of pathological stage, but in the current situation, tumors are clinically understaged in more than half of the cases. Additional clinical tools are needed to provide a firmer base on which the choice for patient treatment or management could be founded. Some of the criteria for the assessment of pathological stage are unclear. For instance, multifocal tumor, which occurs in more than half of the cases of prostate cancer, is not reckoned with in the current system, something that could hamper a correct and unambiguous assessment of pathological stage. In this report, we also discuss the criteria for extraprostatic extension, seminal vesicle invasion, and bladder neck invasion. Follow-up data obtained from a group of 123 patients that underwent radical prostatectomy at our hospital underline the importance of reporting the latter two., (Copyright 2000 Wiley-Liss, Inc.)

Purpose: Although early detection of prostate cancer by prostate specific antigen based screening results in a shift towards more clinically organ confined tumors, changes in prostate cancer characteristics after radical prostatectomy are less clear., Materials and Methods: We studied 121 totally embedded radical prostatectomy specimens that were obtained from consecutive participants of the European Randomized Study of Screening for Prostate Cancer who were systematically screened and treated surgically. In each specimen pathological stage, Gleason score and proportion of high grade cancer (Gleason pattern 4 or 5) were determined. Lymph node status at operation, stage and grade were compared to a historical series of 72 surgical procedures performed for clinically localized prostate cancer at our hospital before the introduction of serum prostate specific antigen as a diagnostic tool., Results: Although none of the screen detected cases had positive lymph nodes at surgery, operation was discontinued in 13 (18%) of the 72 historical cases because of positive lymph nodes. Compared with the remaining 59 historical prostatectomy specimens, the screen detected specimens showed a definite increase in the frequency of pathologically organ confined tumors and a relative decrease in Gleason score 8 to 10 tumors. However, 60% of screen detected tumors contained areas with high grade cancer (Gleason pattern 4 or 5) and 50% had a Gleason score of 7. The relative amount of high grade cancer in each tumor was related to volume (Kruskal-Wallis test p <0. 001)., Conclusions: Screening for prostate cancer leads to an increase in surgical treatment for relatively small tumors that have a higher probability of being organ confined. Although the frequency of positive lymph nodes at operation decreases dramatically and the proportion of organ confined tumors after surgery increases, there is a shift from Gleason 8 to 10 tumors towards lower grade tumors at radical prostatectomy. Still, judged by the high frequency of focal dedifferentiation in screen detected tumors, most of them and surgically treated tumors are likely to be clinically important. The relatively large accumulation of these tumors in the Gleason 7 category is a concern because it could lead to a decrease in the clinical usefulness of the Gleason score system.

Purpose: At low prostate specific antigen (PSA) the indication for prostate biopsy is usually an abnormal digital rectal examination. We evaluate the diagnostic value of PSA, digital rectal examination, transrectal ultrasonography and tumor characteristics at low PSA (0 to 4.0 ng./ml.). We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed., Materials and Methods: From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were randomized to screening in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Of the participants 9,211 (87.5%) had PSA less than 4.0 ng./ml., and underwent digital rectal examination and transrectal ultrasonography. Expected rates of prostate cancer detection were calculated using logistic regression analysis. Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer. Tumors were characterized by pT category, Gleason score and cancer volume in 166 processed radical prostatectomy specimens. In 50 of these cases PSA was 0 to 4.0 ng./ml., Results: The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml. was only 9.7%. Positive predictive value strongly depended on PSA. Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers. Of 760 detectable cancers 478 (67%) were diagnosed irrespective of PSA in men screened with digital rectal examination, transrectal ultrasonography and PSA. Only 127 of 348 detectable prostate cancers (36.5%) were actually diagnosed in men with PSA 2 to 4 mg./ml. The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges., Conclusions: Approximately half of the tumors missed with PSA 0 to 4 ng./ml. had aggressive characteristics (Gleason score 7 or greater, Gleason 4-5 components) and were organ confined. These tumors should be diagnosed and treated according to the present understanding of their natural history. More sensitive and selective screening strategies are needed. Presently a wrong "window of opportunity" is used for early detection of prostate cancer.

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.

Human prostate-specific transglutaminase (hTGp) is a cross-linking enzyme, the physiologic function of which has not been established unequivocally yet. To gain insight into its distribution, we raised antisera against hTGp. By using Western blotting analysis, we found that these antisera specifically recognize a 77-kDa protein in prostatic fluids, seminal plasmas, and prostatic tissues. The concentrations of hTGp in these fluids and tissues were found to be highly variable among individuals. Immunohistochemical examination of several formalin-fixed paraffin-embedded human tissues revealed an exclusive expression in the prostate. The histologic localization and distribution of hTGp within the prostate was assessed by studying multiple sections from tumor-containing prostatectomy specimens and needle biopsies. hTGp expression was entirely restricted to luminal epithelial cells. No basal epithelial cells or stromal cells were stained. Within the prostate, large areas without any hTGp-positive cells were seen. Immunopositive cells were present either in a scattered pattern or concentrated in single or multiple glands in which all luminal epithelial cells expressed hTGp. The latter staining pattern occurred frequently, but not exclusively, in the peripheral zone, whereas scattered expression was most often observed in the transitional zone. Expression of the hTGp protein could occasionally be observed in high-grade prostatic intraepithelial neoplasia, but was not detected in prostate carcinoma cells. The expression pattern as observed for hTGp has not been found thus far for any other prostate-specific marker.

Background: The finding of isolated high grade prostatic intraepithelial neoplasia (PIN) or borderline lesions (lesions suspicious for malignancy) in prostate needle biopsies warrants repeat biopsies. The reported frequency of these lesions in prostate needle biopsies varies considerably. The authors evaluated the frequency and clinical impact of high grade PIN and borderline lesions in sextant prostate needle biopsies obtained from screened participants in the European Randomized study of Screening for Prostate Cancer (ERSPC)., Methods: A total of 8763 participants in the Rotterdam section of the ERSPC ages 55-75 years were screened systematically for prostate carcinoma. Systematic sextant prostate needle biopsies were prompted by an abnormal digital rectal examination and/or abnormal transrectal ultrasonography findings at serum prostate specific antigen (PSA) levels > or = 1.0 ng/mL or a PSA level > or = 4.0 ng/mL. Repeat biopsies were obtained within 6 months after initial biopsy., Results: Of 1824 biopsied men, 384 (21.1%) were found to have prostate carcinoma on initial biopsy. Twelve participants (0.7%) had isolated high grade PIN and 43 (2.4%) had borderline lesions. Repeat biopsies yielded no carcinoma in 7 participants with initial high grade PIN and 15 tumors (38.5%) in 39 participants with borderline lesions., Conclusions: In prostate needle biopsies obtained from a screened population, indications for repeat biopsy such as high grade PIN and borderline lesions do not represent large diagnostic subsets. Borderline lesions comprise the most important indication for a repeat biopsy. The low frequency of equivocal biopsy diagnoses in the current study supports the clinical applicability of sextant needle biopsies in population-based screening for prostate carcinoma.

Purpose: We describe the yield of a repeat examination and biopsy procedure 1 year after initial biopsy was negative. We also assessed the parameters responsible for the failure to diagnose these cancers at the primary screening., Materials and Methods: We screened 8,103 men randomized to the screening arm of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer using prostate specific antigen measurement, digital rectal examination and transrectal ultrasound. At the primary screening biopsy of 1,875 men was positive for prostate cancer in 374. Of the remaining 1,501 men 984 underwent repeat screening., Results: Biopsy at repeat screening diagnosed prostate cancer in 49 of 442 men (11%), a rate significantly lower than the 19.9% true positive biopsy rate at the primary screening. Pathological characteristics of the tumors diagnosed were not significantly different in the 2 groups. However, prostate volume in men diagnosed with prostate cancer was significantly greater at repeat versus primary screening (mean 42.6 versus 34.9 cc, p = 0.003). The clinical characteristics were more favorable because of an increased proportion of stage T1C tumors. Prostate volume in men with stage T1C cancer was significantly greater than in those with palpable or visible tumors in whom prostate specific antigen values were in the same range., Conclusions: The most important factor responsible for the failure to diagnose these cancers at the primary screening was significantly greater prostate volume. Tumor characteristics were not significantly different in the groups. If prostate cancer screening were to become a routine health care policy, efforts would have to be made to improve the chances of diagnosing prostate cancer in larger prostates by repeat biopsy or by increasing the number of cores obtained.

Objective: To evaluate androgen receptor (AR) levels to predict endocrine therapy response and prognosis., Study Design: A sepharose microsphere model was employed to establish the relationship between level of immunohistochemical staining density and both antigen and primary antibody (F39.4.1) concentration. Subsequently, the results of the model system were compared with the results in routine prostate sections., Results: A log-linear relationship was observed between optical density (OD) and primary antibody dilution measured in immunostained, antigen-coated microspheres with moderate antigen density. Similar titration curves were observed in prostate sections at the same dilution range, indicating that the microsphere model can be extrapolated to routine tissue sections. With microspheres with high coating density, the loglinear range of dilutions shifted to higher dilutions., Conclusion: Differences in AR levels in prostate tissue sections might be more accurately detected by comparison of titration curves of primary antibody than by comparison of OD values at a fixed primary antibody dilution.

Objectives: To compare the discriminatory potential between prostate cancer and benign conditions of the prostate in a population-based screening study, of serum prostate-specific antigen levels (PSA) and PSA corrected for both the total prostate volume (PSA-D) and the transition zone volume (PSA-T)., Methods: In a randomized population-based screening study (Rotterdam section of the European Randomized Study of Screening for Prostate Cancer), in which 10,865 men have been screened, the biopsy results of 1202 men with PSA levels of 4 ng/mL or more were evaluated. Planimetric and prolate ellipsoid volumes of the total prostate as well as of the transition zone were measured. The measured volumes were compared with the volumes of 57 radical prostatectomy specimens through Spearman's rank correlation coefficient and agreement tests. A receiver operating characteristic (ROC) curve analysis was done of sensitivity and specificity of biopsy indications through PSA and PSA corrected for the volumes measured with transrectal ultrasound., Results: In the 1202 men studied, 361 cases of prostate cancer were diagnosed. Both PSA-D and PSA-T showed a significantly higher area under the ROC curve (0.77 and 0.79, respectively) than PSA alone (area 0.65). There was no significant difference between PSA-D and PSA-T. The use of a PSA-D threshold value of 0. 10 ng/mL/cc would have avoided 28% of biopsies at the cost of 10% of detectable cancers. A PSA-D threshold of 0.15 ng/mL/cc would have avoided 73.8% of biopsies at the cost of not diagnosing 43.8% of detectable cancers., Conclusions: The planimetrically obtained prostate volume showed a more favorable agreement with the radical prostatectomy volume than the prolate ellipsoid volume. The discriminatory potential of the corrected PSA value is better at predicting the results of needle biopsy of the prostate when compared with PSA alone. The use of the transition zone volume for this correction results in a higher discriminatory potential when compared to the use of the total prostate volume; however, the observed difference was not statistically significant.

In recent years the introduction of serum prostate-specific antigen (PSA) determination as a screening tool for early detection of prostate cancer in asymptomatic men has led to a markedly increased detection of prostate cancers that are neither palpable nor visible with transrectal ultrasonography (stage T1c). In this preliminary study we assessed pathologic features and aspects that are indicative of clinical significance in T1c tumors and tumors with palpable or visible lesions (non-T1c tumors). Between June 1994 and December 1995, 51 consecutive radical prostatectomies were performed on screened participants in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). After determination of pathologic stage and Gleason score, morphometric analysis was performed to determine tumor volume. Radical prostatectomy specimens were divided into three mutually exclusive subsets: T1c tumors, non-T1c tumors with preoperative PSA levels below 4 ng/ml, and non-T1c tumors with PSA levels equal to or greater than 4 ng/ml. These subsets were compared for differences in the distribution of tumor volume, pathologic stage, and Gleason score. An arbitrarily constructed categorization model was used to assess clinical significance. In all, 17 (33%) of the patients had clinical stage T1c disease. In our categorization mode, 88% of the T1c tumors fit the criteria for clinically significant tumors. T1c tumors, however, were significantly smaller (P < 0.01) and were more likely to be organ-confined (P = 0.01) as compared with non-T1c tumors in patients with an elevated preoperative serum PSA level. In contrast, tumors detected at preoperative PSA levels of < 4 ng/ml had comparably the lowest pathologic stages and tumor volumes in our series. In our categorization model, 42% of these tumors fit the criteria for minimal tumor. This group of radical prostatectomies was therefore most likely to harbor clinically insignificant cancer, a finding that was consistent in two other categorization models derived from earlier reports. T1c tumors comprise a large fraction of the tumors found in population-based screening. As judged by their pathologic characteristics. T1c tumors are clinically significant tumors. The overall low pathologic stage and Gleason score of these tumors make these patients excellent candidates for curative treatment by radical prostatectomy or radiotherapy. In contrast, some concern should be raised on the detection of tumors at low serum PSA levels by means of digital rectal examination and transrectal ultrasound alone, since a substantial proportion of these tumors could be considered clinically insignificant. Long-term follow-up, however, is necessary to substantiate this view.