Features of prostate cancers detected during a prevalence screening round. The Rotterdam experience.

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.

[Diagnosis based on prostate needle biopsy: inadequate correlation between pathologic results and clinical course for individual prognosis]. / Diagnostiek op prostaatbiopten: onvoldoende verband tussen pathologische uitslag en klinisch beloop voor een individuele prognose.

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.

Guidelines for processing and reporting of prostatic needle biopsies.

The reported detection rate of prostate cancer, lesions suspicious for cancer, and prostatic intraepithelial neoplasia (PIN) in needle biopsies is highly variable. In part, technical factors, including the quality of the biopsies, the tissue processing, and histopathological reporting, may account for these differences. It has been thought that standardisation of tissue processing might reduce the observed variations in detection rate. Consensus among the members of the pathology committee of the European Randomised study of Screening for Prostate Cancer (ERSPC) concerning the optimal methodology of tissue embedding resulting in guidelines for prostatic needle biopsy processing was reached. The adoption of an unequivocal and uniform way of reporting lesions encountered in prostatic needle biopsies is considered helpful for decision taking by the clinician. The definition of parameters for quality control of prostatic needle biopsy diagnostics will further facilitate clinical epidemiological multicentre studies of prostate cancer.

The clinical significance of a small focus of well-differentiated carcinoma at prostate biopsy.

OBJECTIVE: To compare a series of 121 sextant needle biopsy sets with their corresponding radical prostatectomy specimens in screened participants in the European Randomized study of Screening for Prostate Cancer (ERSPC), investigating the effect of screening for prostate cancer on disease-specific mortality and quality of life, as the clinical significance of a small focus of well-differentiated prostate cancer on biopsy is unclear. PATIENTS AND METHODS: The expected clinical significance of the discovered tumours was estimated using an arbitrary model combining volume, grade, and stage characteristics. RESULTS: Of 34 patients who had a small focus (< 3 mm on a single biopsy core) of well-differentiated carcinoma on biopsy, only 18 (53%) were found to have minimal carcinoma (a small focus of well-differentiated carcinoma) at radical prostatectomy, while 16 (47%) had moderately advanced or advanced carcinoma at radical prostatectomy. The preoperative prediction of minimal carcinoma improved when the amount of cancer in the sextant biopsy set was combined with the preoperative serum prostate specific antigen (PSA) level. Of 12 patients with a small focus of well-differentiated carcinoma on biopsy and a serum PSA of < 4 ng/mL, 11 had minimal carcinoma at radical prostatectomy, while there was minimal carcinoma in only seven of 22 (32%) patients with a small focus of well-differentiated carcinoma on biopsy and a serum PSA of > or = 4 ng/mL. CONCLUSIONS: The predictive value of a small focus of well-differentiated cancer on systematic sextant biopsy for a small well-differentiated tumour in the prostate is limited. The predictive value improves when serum PSA levels are considered concurrently, but is still considered insufficient to support a base for selecting therapy for the individual patient.

Consistency of prostate cancer grading results in screened populations across Europe.

OBJECTIVE: 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. PATIENTS AND METHODS: 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 < or = 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. RESULTS: Combining the data of seven ERSPC centres 66% of cancers detected in the screening arm were Gleason score < or = 6 and 92% were < or = 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. CONCLUSIONS: 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.

The predictive value for prostate cancer of lesions that raise suspicion of concomitant carcinoma: an evaluation from a randomized, population-based study of screening for prostate cancer.

BACKGROUND: Suspicion of prostate carcinoma may persist after an initial negative biopsy result, and repeated biopsy is suggested. The authors assessed whether diagnostic follow-up of men with an initial diagnosis of isolated, high-grade prostatic intraepithelial neoplasia (HPIN) and a prostate biopsy suspicious for malignancy (PBSM) is needed. METHODS: The frequency of isolated HPIN and PBSM was determined in 4057 participants of a population-based screening study who underwent systematic sextant transrectal biopsy. The predictive value for prostate carcinoma of HPIN and PBSM was determined by performing repeated biopsies at 6-week interval. The additional predictive value for malignant disease within a screened population was assessed by performing repeated biopsies at a 1-year interval in 462 consecutively recruited men with an initial benign biopsy result. Participants were subjected to a second screening at a 4-year interval. The biopsy and radical prostatectomy tumor features were determined. RESULTS: Isolated HPIN and PBSM were diagnosed in 0.8% and 2.6% of biopsied men, respectively. The detection rates on repeated biopsy were 10.0% (3 of 30 men) for isolated HPIN, 38.7% (36 of 93 men) for PBSM, and 11.0% (51 of 462 men) for those with initial benign biopsy results. Except for two men (one with PBSM and one with HPIN), all others remained free of prostate carcinoma at their second screening. Features of the tumors that were detected after PBSM were comparable to those that were detected on initial biopsy, whereas the few tumors that were diagnosed after HPIN had highly favorable features. CONCLUSIONS: Compared with men who have PBSM, men with isolated HPIN on initial biopsy are at no greater risk of being diagnosed with prostate carcinoma than if their initial biopsies were assessed as benign only. Moreover, the features of tumors that are diagnosed after an evaluation of HPIN warrant no early, extensive diagnostic follow-up.

Pathologic features of prostate cancer found at population-based screening with a four-year interval.

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.

Tumor characteristics in screening for prostate cancer with and without rectal examination as an initial screening test at low PSA (0.0-3.9 ng/ml).

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.

Molecular cytogenetic analysis of prostatic adenocarcinomas from screening studies : early cancers may contain aggressive genetic features.

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.

Defining the window of opportunity in screening for prostate cancer: validation of a predictive tumor classification model.

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.

Staging prostate cancer.

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.

Detection of prostate cancer: a comparative study of the diagnostic efficacy of sextant transrectal versus sextant transperineal biopsy.

OBJECTIVES: The optimal biopsy strategy for the detection of prostate cancer still needs to be established, since a considerable proportion of clinically significant cancers remains undiagnosed on routine sextant transrectal biopsy. To assess the efficacy of transperineal biopsy to detect prostate cancer, we compared this approach to systematic sextant transrectal biopsy in a simulation experiment. METHODS: Ultrasound-guided sextant transverse (transrectal) biopsy and subsequent sextant longitudinal (transperineal) biopsy were performed on 40 radical prostatectomy specimens of patients with (transrectal) biopsy-detected prostate cancer. Conditions were simulative and may not be completely analogous to clinical settings. Ultrasound-determined prostate volume, biopsy tumor involvement, number of cores with cancer, and tumor volume were determined. Detailed mapping of radical prostatectomy specimens provided insight into the representativeness of the biopsy techniques. RESULTS: Of 40 cancers, 33 (82.5%) were redetected by the transperineal approach; 29 (72.5%) were detected by repeated transrectal biopsies. For both approaches, the tumor volume of the undiagnosed cancers was significantly smaller (P <0.01) and the prostate volume was significantly larger (P <0.01) than in the redetected ones. Between the two approaches, no difference was found for either of the variables determined in the redetected cancers. Prostate maps clarified that transperineal undiagnosed tumors were either small (0.2 cm(3) or less) or notably located at the prostatic base. CONCLUSIONS: The biopsy procedure in which the biopsy needles enter the prostate at the apex for a longitudinal direction may efficiently sample the prostatic peripheral zone. Since the experiment was artificial in design, caution should be observed in extrapolating these results to patient settings.

Histopathological prostate cancer characteristics at radical prostatectomy after population based screening.

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.

Prostate cancer detection at low prostate specific antigen.

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.

Human prostate-specific transglutaminase: a new prostatic marker with a unique distribution pattern.

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.

The changing pattern of prostate cancer at the time of diagnosis: characteristics of screen detected prostate cancer in a population based screening study.

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

Evaluation of prostate needle biopsies in a population-based screening study: the impact of borderline lesions.

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.

Evaluation of the digital rectal examination as a screening test for prostate cancer. Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.

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.