http://repub.eur.nl/res/aut/10003/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/36008/ 2007-11-01T00:00:00Z Objectives: The purpose of screening for prostate cancer is to decrease the disease-specific mortality. However not every screen-detected prostate cancer is a threat to the patient's life. The risk of overdetection and subsequent overtreatment in prostate cancer has been recognised. The purpose of this investigation was to evaluate the role of tumour markers total PSA, free PSA, and hK2, and their combinations in predicting minimal prostate cancer. Methods: Within the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, The Netherlands, prebiopsy serum samples were analysed for 100 selected men who underwent a radical prostatectomy for their screen-detected prostate cancer. All had a PSA value between 4 and 10 ng/ml prior to diagnosis. Minimal prostate cancer is defined as organ confined, Gleason score ≤6 (no Gleason grade 4 or 5), and tumour volume <0.5 ml. Results: Sera and tumour volumes from 91 men were available for analysis. Minimal prostate cancer was diagnosed in 16.5% of the selected cases. Mean tumour volume was 1.2 ml (range: 0.04-13.5); hK2, the algorithms hK2/fPSA, and hK2/%fPSA have significant correlations with tumour volume. Both algorithms also yielded the best test results in predicting minimal disease with an area under the receiver operator characteristics curve of 82%. Conclusions: hK2 and percent free PSA have added prognostic value for the detection of minimal prostate cancer in screen-detected cases within PSA range 4-10 ng/ml. These biomarkers can possibly be used to select less invasive treatment options like active surveillance and to prevent overtreatment. http://repub.eur.nl/res/pub/36066/ 2007-07-01T00:00:00Z Objectives: To evaluate the features, rates, and characteristics of prostate cancer detected during two subsequent screening rounds. Methods: Data were retrieved from the database of European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. Men, ages 55-74 yr were screened with a 4-yr interval. Different biopsy indications were used in the first and second screens in the PSA range <4.0 ng/ml. Clinical features and a total of 1548 sextant biopsies were recorded for Gleason score and tumour extent, and 550 radical prostatectomy specimens were evaluated for Gleason score, pathologic T category, and tumour volume. Results: Clinical stage, Gleason score, involvement of biopsy by tumour, and PSA levels were more favourable in patients of the second round compared with those of the first round. The number of men chosen for watchful waiting increased from 98 (10%) to 123 (22%) in the second round (p < 0.0001). In patients undergoing radical prostatectomy, median tumour volume in the first and second screening round was 0.65 and 0.45 ml (p = 0.001). Minimal cancer (cancer <0.5 ml, organ-confined, no Gleason pattern 4 or 5) was found in 122 (31.6%) in the first and 60 (42.6%) in the second screening round (p = 0.03). The 5-yr PSA progression-free survival after radical prostatectomy was 87%. Conclusions: Despite the 4-yr interval an important shift of all prognostic factors occurred in favour of round 2. In those men who underwent radical prostatectomy, 42.6% fulfilled the criteria of minimal cancer. These data suggest that overdiagnosis increases with repeat screening. http://repub.eur.nl/res/pub/36134/ 2007-02-01T00:00:00Z Introduction: This report describes survival data of participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, diagnosed with prostate cancer (pCA) during the first round of screening, the prevalence screen. Patients and methods: pCA characteristics from cases diagnosed during the first screening round from December 1993 to March 2000 are shown. During follow-up, data were collected by semiannual patient chart review for the first 5 yr and annually thereafter. The causes of death are scored according to the diagnosis of the treating physician and are not based on the review of the independent causes-of-death committee. Overall and disease-specific survival graphs are shown in Kaplan-Maier projections and compared with expected survival outcomes for males in the same age categories from the Dutch provinces of North Holland and Flevoland. Statistical evaluation was based on Cox regression analysis. Results: During the prevalence screening, 1014 patients were diagnosed with pCA. Median follow up was 55 mo, 126 (12.4%) patients died, 20 (2.0%) of pCA. Overall 5-yr observed and expected disease-specific survival was 97.7% and 82%, respectively. In the multivariate analysis, a Gleason sum of 4+4 or higher (p = 0.025) was predictive of pCA death. Conclusions: The observed survival data are in line with the literature and the expected favorable outcome for a screened population. The proportion of men dying from pCA is still small, and a 10-yr follow-up period for the final evaluation of the ERSPC may be too short. http://repub.eur.nl/res/pub/7662/ 2006-04-12T00:00:00Z Prostate cancer is nowadays the most common non-cutaneous cancer in men in the Western world. Since the introduction of Prostate Specific Antigen (PSA) testing in the last decade, prostate cancer incidence increased dramatically. In addition, the population is aging, and prostate cancer incidence increases with higher age. The dilemma of prostate cancer is that more men die with prostate cancer than from prostate cancer, as reflected by the observation that in 70% of men who are 80 years or older prostate cancer is diagnosed histologically on autopsy. As a consequence of this high incidence on autopsy, it may be anticipated that a large proportion of old men are diagnosed with prostate cancer when undergoing prostate biopsy and a great proportion of prostate cancers detected in screening programs may be over-diagnosed. It is as yet unclear whether PSA based screening reduces prostate cancer mortality. Due to screening with PSA most cancers are diagnosed in an early stage and therefore possibly in a curable stage. As a result, cancer is removed in an early stage, before the tumor is able to metastasize. It is conceivable that population-based early prostate cancer screening will reduce prostate cancer mortality. In order to investigate this further, randomized clinical trials have been introduced. In the USA the Prostate Lung Colorectal and Ovary cancer (PLCO) study investigates if prostate cancer screening is justified. In Europe the European Randomized Study of Screening for Prostate Cancer (ERSPC) is conducted in 8 European countries to study whether prostate cancer screening can reduce prostate cancer specific mortality at affordable costs and quality of life. The European screening centers differ with regard to the screening procedure but they share PSA testing and most other features (Table 1). At the Rotterdam section of the ERSPC the screening protocol comprises serum PSA testing followed – in case of an elevated serum PSA level- by six lateralized needle biopsies, three from each side of the prostate (systematic sextant biopsy) in men aged between 55 and 75 years. Every four years the same cohort of men is screenend. Men are excluded from screening in the 2nd round if a previous diagnosis of prostate cancer is made and those with interval carcinoma (i.e. cancers detected after the 1st round, but during the 4-year screening interval period. Unfortunately, the final outcome of the ERSPC will not be here until the end of 2008 or later. This thesis is restricted to an analysis of the data from first and second screening rounds at the Rotterdam section of the ERSPC. Awaiting the final outcome of the ERSPC, the investigations collected in this thesis are aimed to provide insight in 1) intermediate endpoints, concerning stage and grade of prostate cancer in subsequent screening rounds and the forthcoming therapy choices, 2) the efficiency of the screening protocol employed at the Rotterdam section of the ERSPC and 3) the natural biology of prostate cancer and its possible premalignant lesions. http://repub.eur.nl/res/pub/14403/ 2004-08-13T00:00:00Z OBJECTIVES: We conduct a longitudinal non-invasive study of changes in urinary bladder contractility secondary to benign prostatic enlargement. In that study, the prostate volume is estimated by transabdominal ultrasonography. The accuracy of those measurements was verified by comparison of transabdominal to transrectal stepwise planimetric ultrasonography as the gold standard. Also, two different transabdominal devices used were compared, and the influence of different operators was studied. MATERIALS & METHODS: Two series of measurements in 100 patients each were done. In the first series, transabdominal and transrectal sonography were pairwise compared in each patient. In the second series, transabdominal measurements were done with two devices (a hospital Aloka SSD-1700 and a portable Aloka SSD-900). Transrectal scannings were done by three investigators whilst all transabdominal scannings were done by one. Regression graphs, ratio plots and statistical analyses of the data quantified the reproducibility of different methods, observers and device types. RESULTS: In the transrectal-transabdominal series of prostate volume measurements (in cm3), the Pearson correlation coefficient was 0.84 (p < 0.001), the mean of the means was 51.8 +/- 23.0 (mean +/- S.D.), and the mean of the differences was 1.0 +/- 1.4. In the series with two devices, the Pearson correlation coefficient was 0.73 (p < 0.001), the mean of the means was 31.0 +/- 10.9, and the mean of the differences was 1.0 +/- 1.3. CONCLUSION: No statistically significant differences were found between the transabdominal- transrectal ultrasonography, two different transabdominal devices nor between different observers. However, for those using these measurements in everyday clinical practice, it is worth to point out that in our data a transabdominal scan and a transrectal scan in the same patient, on the same day, differed more than 30% in one fourth of the patients and that two transabdominal scans in the same patient (with two different devices, on two different days) differed more than 30% in every fifth patient