Comparison of Classic and International Society of Urological Pathology 2005 Modified Gleason Grading Using Needle Biopsies From the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) Trial

Abstract

Objective.-To compare scores derived using the 2 scoring systems.Design.-On-study and for-cause biopsies were centrally reviewed and assigned a classic Gleason score in the Reduction by Dutasteride of prostate Cancer Events trial. Positive biopsies were reviewed by an independent pathologist in a secondary review using the ISUP 2005 modified Gleason score. The independent pathologist also recorded a classic Gleason score.Results.-In total, 1482/1507 (98%) positive biopsy results were independently reviewed. Scores assigned by the 2 pathologists (classic versus modified) agreed in 83% (1230 of 1481) of cases; 99% (1471 of 1481) of cancers were within 61 of their previous score. Of discordant cases, similar numbers of biopsies were upgraded and downgraded in the secondary review, with minor differences in the score distributions. Interobserver agreement was good, with j values ranging from 0.62 (95% confidence interval [CI], 0.56-0.67) to 0.70 (95% CI, 0.65-0.76). The overall number of high-grade tumors (Gleason score 8-10; n ¼ 48) remained constant between reviews, with 3 fewer cases in the placebo group (n ¼ 16) and 3 more in the dutasteride group (n ¼ 32) in the secondary review. When comparing the independent pathologist's modified scores versus the classic, 17 of 1481 cancers (1.1%) were upgraded (including 9 of 17 upgrades [53%] to high-grade tumors).Conclusions.-This analysis showed similar score distributions between the classic and modified Gleason scoring systems. The differences seen between the 2 pathologists' scores likely reflect differences in interpretation rather than the scoring system chosen.

On the relationship between tumor structure and complexity of the spatial distribution of cancer cell nuclei: A fractal geometrical model of prostate carcinoma

“…The second parameter seems to be well correlated with clinical outcome [13]. However, the subjectivity of tumor grading leads to the significant inter-and intra--observer variability of 40-80% [14][15][16][17][18][19] associated with the coefficient k for interobserver agreement 0.15-0.7 [15,[20][21][22]. Second, the natural history of prostate cancers shows that 30-75% of localized prostate cancers are low-grade, low-risk, and slowly growing carcinomas with the low cancer-specific mortality [23][24][25].…”

“…There are some other essential reasons for the large inter-and intra-observer variability in grading of prostate carcinomas [14][15][16][17][18][19][20][21][22]. First, there are many histological details, such as density of cellular infiltra-tion or a number of pseudo-glands that cannot be evaluated by human mind and eyes quantitatively with sufficient precision.…”

An audit of inter-observer variability in Gleason grading of prostate cancer biopsies: The experience of central pathology review in the North West of England

“…This agreement, in general, has been seen to be high amongst urological pathologists than in general pathologists [16]. In a recent study, a kappa value of 0.7 was reported reflecting the experience of pathologists involved in the study [2]. In a study by Mulay et al, an agreement 0.36-0.64 was reported but the value increased after a simple web-based training, thus indicating the value of training in reducing the level of disagreement in the interpretation of prostate biopsies [14,15].…”

“…In the histological reporting of prostate cancer, Gleason scoring system is an important prognostic parameter for therapeutic decision and in the overall management of prostate cancer patients [2] and it has emerged as a strong predictor of recurrence and prediction of organ-confined disease [3]. In 2005, the ISUP introduced modifications of Gleason scoring system [4] one of which include assigning any cribriform pattern to grade 4 and this has been shown to decrease the under grading observed in biopsies when compared to the prostatectomy specimens.…”

The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas

“…It is a challenge for pathologists to match the images to the definition of a grade, especially in the borderline cases (reviewed in Montironi et al, 2013 ). The subjective tumor grading has a significant inter- and intraobserver variability in the range of 38–80% (Nguyen et al, 2004 ; van der Kwast et al, 2010 ; McKenney et al, 2011 ; Netto et al, 2011 ; Egevad et al, 2013 ; Berney et al, 2014 ) and the coefficient κ for interobserver agreement 0.15–0.7 (McLean et al, 1997 ; Allsbrook et al, 2001 ; van der Kwast et al, 2010 ; McKenney et al, 2011 ; Scott Lucia et al, 2013 ). Even though some DNA-, RNA-, or protein biomarkers were co-applied, it did not improve the accuracy of grading.…”