Can non-malignant biopsy features identify men at increased risk of biopsy-detectable prostate cancer at re-screening after 4 years?

OBJECTIVES: To identify pathological features in non-malignant sextant prostate needle biopsies and assess their predictive value for detecting prostate cancer on biopsy 4 years later. PATIENTS AND METHODS: We selected and reviewed the biopsy specimens of 121 men that were diagnosed as non-malignant during the first screening round of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam section. Of these 61 (50.4%) were positive for cancer during the second round (the result of a matched random sample). The biopsies were indicated by prostate-specific antigen levels of >or= 3.0 ng/mL. Specimens were scored for high-grade prostatic intraepithelial neoplasia (HGPIN), active and chronic inflammation, biopsy core length and glandular core length. The predictive value of the pathological features for detecting prostate cancer after 4 years was assessed. RESULTS: In the first-round biopsies the incidence of HGPIN was 7.1%; there was active inflammation in 22.4% and chronic inflammation in 51.0%. The mean core length was 9.3 mm and mean glandular core length 7.4 mm; the mean total biopsy length (sum of core lengths) was 56.3 mm and mean total glandular length (sum of glandular core lengths) was 44.6 mm. None of the pathological features in the initial round was significantly related to the detection of cancer in the second round. CONCLUSIONS: In this study of non-malignant prostate biopsy specimens from a screened population, no pathological features could be identified that were predictive for detecting prostate cancer on biopsy 4 years later.

Tumor characteristics and prognostic factors in two subsequent screening rounds with four-year interval within prostate cancer screening trial, ERSPC Rotterdam.

OBJECTIVES: To evaluate the tumor characteristics and prognostic factors in screen-detected prostate cancers in two successive screening rounds with a 4-year screening interval in the European Randomized Study of Screening for Prostate Cancer, section Rotterdam. METHODS: From 1993 to 2000, 42,376 men (21,210 in the screening arm and 21,166 in the control arm) were randomized and screened. Prostate-specific antigen testing, digital rectal examination, transrectal ultrasonography, and sextant biopsies were offered to the participants in the screening arm. A total of 1218 men with a biopsy indication at the first screening received an additional screening after 1 year (early recall). By 2004, all men had received their second screening. Interval carcinomas were defined as cancers detected during the screening interval and were identified by linkage with the Cancer Registry. RESULTS: In the first round, 1014 prostate cancers were detected--24 in the men noncompliant to screening, 63 at the early recall screening, and 433 in the second round of screening. Also, 62 interval carcinomas were diagnosed. In the second screening round, the mean prostate-specific antigen value was lower (5.6 versus 11.1 ng/mL), advanced clinical stage T3-T4 was 7.1-fold less common, and 76.4% versus 61.5% of the biopsy Gleason scores were less than 7. In the first screening round, 13 regional and 9 distant metastases were detected; in the second round, 2 cases with distant metastasis were found. CONCLUSIONS: Overall, a shift toward more favorable tumor characteristics was seen for the second round of screening. These results support the screening methods used and the interscreening interval of 4 years.

Comparison of screen detected and clinically diagnosed prostate cancer in the European randomized study of screening for prostate cancer, section rotterdam.

PURPOSE: This report provides a comparison of characteristics detected in the screening and control arms of the European Randomized study of Screening for Prostate Cancer, section Rotterdam. MATERIALS AND METHODS: Between December 1993 and January 1999, 35,148 men 55 to 74 years old were randomized to European Randomized study of Screening for Prostate Cancer Rotterdam, including 17,635 in the screening arm and 17,513 in the control arm. Prostate specific antigen testing, digital rectal examination, transrectal ultrasound and sextant biopsies were offered to all participants in the screening arm according to 2 algorithms. All screening detected cancers and cancers found in the control arm were evaluated at the same cutoff point, that is January 1, 2003. To identify prostate cancer cases in the control arm yearly linkage was performed with the Rotterdam Cancer Registry database. Followup information was collected by chart review. RESULTS: By January 1, 2003, 1,269 cancers were detected in the screening arm and 336 were detected in the control arm. A shift to more favorable clinical stages and histological grades on biopsy was seen in the screening arm of the trial. T1C and T2 cancers were 5.8 and 6.2 times more often diagnosed, respectively, in the screening arm than in the control arm of the trial. Only 4.6% of control arm cancers were found through opportunistic screening. CONCLUSIONS: Although a favorable shift in prognostic factors was seen for the screening arm of the trial, these results do not provide evidence that prostate cancer screening has an effect on prostate cancer mortality.

Interval carcinomas in the European Randomized Study of Screening for Prostate Cancer (ERSPC)-Rotterdam.

BACKGROUND: The interval cancer rate is an important parameter for determining the sensitivity of a screening procedure and the screening interval. We evaluated the time and mechanism of detection and the stage distribution of interval prostate cancers diagnosed during a 4-year screening interval. METHODS: We determined the rate of interval cancers and the sensitivity of the screening protocol (involving prostate-specific antigen, digital rectal and transrectal ultrasound examinations) in a cohort of 17 226 men (8350 on the screened arm, 8876 on the control arm) enrolled consecutively on the European Randomized Study of Screening for Prostate Cancer-Rotterdam. Men on the screened arm received a first screen between October 1993 and December 1996 and a scheduled second screen 4 years later. Prostate cancers detected in men enrolled on the control arm over the same 4-year period and, between screens, in men on the screened arm, were identified by linkage to the Dutch national cancer registry. RESULTS: During the first screen, 412 prostate cancers were detected. During the subsequent 4-year period, 135 cancers were diagnosed in men in the control arm and 25 cancers were diagnosed in men in the screened arm. Seven of the 25 cancers were diagnosed in men who had refused a recommended biopsy at their initial screen. Of the remaining 18 cancers, all were classified as stage T1A-C or T2A and none were poorly differentiated or metastatic. The rate of interval cancers relative to the number of cancers in the control group was 18.5% (25/135), or 13.3% (18/135), if the seven who refused an initial biopsy were excluded. The sensitivity of the screening protocol was 79.8% when considering all 25 interval cancers and 85.5% when considering 18 interval cancers. CONCLUSION: The interval cancer rate with a 4-year screening interval was low, confirming that the screening procedure has a high sensitivity and that the 4-year screening interval is reasonable.