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

A recent report in the Journal (1) reported on the first two rounds of population-based screening at intervals of 4 years in the European Randomized Study of Screening for Prostate Cancer. A total of 4133 men aged 55–75 years were screened in the first round, and 2385 of these men were screened in the second round, 4 years later. Sextant biopsy specimens were obtained under ultrasound guidance during both rounds of screening, with all cores embedded separately; the total amount of cancer in needle biopsy sets and the percentage of adenocarcinomas of Gleason score 7 or higher were calculated. The main result of Hoedemaeker et al. (1) was that the second round of screening found less cancer (median of 4.1 versus 7 mm in the biopsies) and fewer cancers of Gleason score 7 or higher (median of 16% versus 36%) than the first round of screening. On the basis of these data, the authors assume that the cancers were smaller in the second round of screening than in the first round. However, the U.S. literature is replete with evidence that the amount of cancer found in sextant biopsies of the prostate [such as the sextant biopsies of Hoedemaeker et al. (1)] is unrelated to the volume or grade of the largest (index) cancer in the prostate as determined by radical prostatectomy. For example, a recent study from my group (2) shows the absence of any relationship between the index (largest) cancer volume in 222 radical prostatectomy specimens and the number of positive sextant biopsies, the total length of cancer in the biopsies, and the percentage of cancers with Gleason grade 4/5 in sextant biopsies (Fig. 1). In this study, all 222 biopsies were reviewed by the same expert pathologist who later determined the index (largest) cancer volume from 3-mm step-sections, a protocol we have used at Stanford since 1983 in over 2000 consecutive Fig. 1. A) Correlation between number (No.) of positive cores in biopsies and cancer volume in radical prostatectomy specimens. B) Correlation between total length of cancer in biopsies and cancer volume in radical prostatectomy specimens. C) Correlation between percent of Gleason Grade 4/5 on biopsies and cancer volume in radical prostatectomy specimens. We used 0.5 cc as cutoff for clinically significant cancer volume. Used with permission from American Urological Association Education and Research, Inc.