The Potential Impact of Reproducibility of Gleason Grading in Men With Early Stage Prostate Cancer Managed by Active Surveillance: A Multi-Institutional Study

Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.
The Journal of urology (Impact Factor: 4.47). 06/2011; 186(2):465-9. DOI: 10.1016/j.juro.2011.03.115
Source: PubMed


We evaluated the reproducibility of Gleason grading as relevant to the clinical treatment of men on active surveillance.
Three sets of digital images of prostatic adenocarcinoma in biopsies were reviewed and assigned Gleason scores by a total of 11 pathologists from 7 institutions. Interobserver and intra-observer reproducibility were assessed for assignment of the highest Gleason pattern (3 vs 4 or higher). We also identified 97 consecutive patients on active surveillance. Prostate biopsy glass slides from 82 of the patients were available for re-review and the frequency of carcinoma requiring the distinction of tangentially sectioned Gleason pattern 3 from 4 was determined.
Interobserver reproducibility for classic Gleason patterns was substantial (Light's κ 0.76). Interobserver reproducibility for the histological distinction of tangentially sectioned Gleason pattern 3 from Gleason pattern 4 was only fair (Light's κ 0.27). Intra-observer reproducibility ranged from 65% to 100% (mean 81.5%). Of the 82 patients on active surveillance 61 had carcinoma and 15 (24.5%) had a set of biopsies with at least 1 focus in which the distinction between tangentially sectioned Gleason pattern 3 and poorly formed pattern 4 glands had to be considered.
The reproducibility of grading classic Gleason patterns is high. However, variability in grading occurred when distinguishing between tangentially sectioned pattern 3 glands and the poorly formed gland subset of pattern 4. Developing universally accepted histological and/or molecular criteria to distinguish these patterns and subsequently characterizing their natural history would be useful when treating patients on active surveillance.

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    • "Another reason to implement novel markers in prostate cancer diagnosis and clinical decision-making is the considerable interobserver variability in Gleason grading among pathologists. This interobserver variability is particularly of significance in the large group of low- to intermediate-risk prostate cancer, as it can influence therapeutic approaches [8–10]. Contemporary modified Gleason grading in needle-biopsies demands adding the most common and highest Gleason grade to the final Gleason score, regardless of the amount of “highest” Gleason grade. "
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    • "These include smaller prostates [2] [3], higher PSAs [3] [4], and higher volume cancer at biopsy [5]. In addition, interobserver variability in pathologic interpretation of PCa specimens plays a role in this discordance [6] [7] [8]. Central pathologic review by dedicated genitourinary pathologists has been shown to lead to more accurate grading of the biopsy Gleason score and subsequent higher concordance with RP Gleason score [9]. "
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    ABSTRACT: Objective. To determine whether initial biopsy performed by community or academic urologists affected rates of Gleason upgrading at a tertiary referral center. Gleason upgrading from biopsy to radical prostatectomy (RP) is an important event as treatment decisions are made based on the biopsy score. Materials and Methods. We identified men undergoing RP for Gleason 3 + 3 or 3 + 4 disease at a tertiary care academic center. Biopsy performed in the community was centrally reviewed at the academic center. Multivariate logistic regression was used to determine factors associated with Gleason upgrading. Results. We reviewed 1,348 men. There was no difference in upgrading whether the biopsy was performed at academic or community sites (OR 0.9, 95% CI 0.7-1.2). Increased risk of upgrading was seen in those with >1 positive core, older men, and those with higher PSAs. Secondary pattern 4 and larger prostate size were associated with a reduction in risk of upgrading. Compared to the smallest quartile of prostate size (<35 g), those in the highest quartile (>56 g) had a 49% reduction in risk of upgrading (OR 0.51, 95% CI 0.3-0.7). Conclusion. There was no difference in upgrading between where the biopsy was performed and community and academic urologists.
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  • No preview · Article · Jul 2011 · Nature Reviews Urology
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