Tag Archive for: ISUP grades


Article of the Week: Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000–2012

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000–2012

Daniela Danneman*, Linda Drevin, Brett Delahunt, Hemamali Samaratunga§¶David Robinson**, Ola Bratt††‡‡, Stacy Loeb§§ Par Stattin¶¶*** and Lars Egevad*†††


*Department of Oncology-Pathology, Karolinska Institute, Stockholm, † Regional Cancer Centre, Uppsala University Hospital, Uppsala, Sweden, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand, §Aquesta Pathology, The University of Queensland School of Medicine, Brisbane, Qld, Australia, **Department of Urology, Ryhov County Hospital, Jonkoping, Sweden, ††Department of Urology, Cambridge University Hospitals, Cambridge, UK, ‡‡Department of Translational Medicine, Lund University, Lund, Sweden, §§Department of Urology and Population Health, New York University and Manhattan Veterans Affairs Medical Centre, New York, NY, USA, ¶¶Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea University, Umea, ***Department of Surgical Sciences, Uppsala University, Uppsala, Umea, and †††Department of Pathology, Karolinska University Hospital, Stockholm, Sweden




To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1–5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9–10) better predict the RP grade.

Patients and Methods

All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1–2 M0/X prostate cancer on needle biopsy; were aged ≤70 years; had serum PSA concentration of <20 ng/mL; and underwent a RP <6 months after diagnosis as their primary treatment.



Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001).


Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

Editorial: The prognostic value of prostate biopsy grade – Forever a product of sampling

The ability to project clinical outcomes based on limited data is crucial to the practice of medicine. This principle is particularly germane to the management of prostate cancer, where clinical outcomes vary widely. In the current issue of BJUI, Danneman et al. [1] assess pathological grade concordance between diagnostic needle biopsy and subsequent radical prostatectomy specimens from 2000 to 2012. The authors observed increased concordance of biopsy and prostatectomy Gleason scores over the time period (from 55% in 2000 to 68% in 2012) with the majority of improvement occurring before 2005. Interestingly, concordance decreased over time (from 68 to 57%) with use of the newly revised grading system. These and other findings led to the proposal that increased concordance was attributable more to the elimination of Gleason scores 2–5 than the systematic change in grading itself.

We commend the authors for exploring this important topic. Our ability to derive meaningful information on disease biology and behaviour from biopsy specimens is essential to counselling patients on the many available management options. At the same time, biopsy grading is inherently limited in its ability to predict overall prostate pathology because it is not only dependent on architecture and morphology, but also on the, admittedly minimal, sample of tissue obtained. As such, we should be cautious in using terms such as ‘undergrading’ in describing biopsy specimens, which may have been properly graded, but simply lacked the higher grade tumour observed at prostatectomy. In reality, such a phenomenon represents undersampling rather than undergrading, and there is hope that such undersampling will decrease with improved methods of detection, such as multiparametric MRI/TRUS fusion-guided biopsy.

Notably, the authors refer to the updated grading system, which was first described by Dr Epstein and validated in a multi-institutional study [2] before the 2014 International Society of Urological Pathology (ISUP) consensus conference, as ISUP grades 1–5. For clarity, it should be noted that the initial report and validation of the new system [2], the 2014 ISUP consensus conference proceedings [3] and the WHO 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs [4], have all described the new system based on grade groups 1–5. Consistent use of the adopted terminology will be helpful moving forward.

Nonetheless, there are several potential explanations for the patterns observed in the present study. As the authors note, lower concordance based on the grade group system can be largely explained by the more precise classification of Gleason score 7 cancers. Based on evidence of disparate outcomes in Gleason score 3+4 = 7 and 4+3 = 7 disease [5], the ISUP system distinctly classifies these cancers as prognostic grades 2 and 3, respectively. Certainly, when compared with a system in which Gleason score 7 represents a single classification, one would expect poorer concordance in the more widely distributed group. We believe the clinical utility of separating these classifications far outweighs a modest decrease in concordance, which may be explained by other factors in any case. Previous studies have shown the importance of subdividing the Gleason score 7 population when comparing grading systems [6]. Furthermore, details are not provided as to whether a global grade was assigned to biopsy, a common practice in Sweden, which is not the currently recommended practice. That 5–7% of specimens received a Gleason score < 6 calls into question whether contemporary recommendations were fully adopted during the study period.

Regardless, Danneman et al. elegantly highlight the frequency with which biopsy and prostatectomy grades are discordant, and the fact that, to date, pathological grading remains a subjective practice. As noted, there are widespread efforts to address both of these issues, including the use of targeted biopsies and tissue-based genomic markers. Until these practices are well-validated and widely implemented, there are several reasons to believe the most recent grade group system will improve contemporary practice, despite limited concordance. For one, use of a more intuitive scale ranging from 1 to 5 should prove easier for patients to understand, a significant consideration in light of the information overload patients absorb with a new diagnosis of cancer. Furthermore, available data to this point demonstrate excellent prognostic value. In one study from Johns Hopkins, the revised Grade Group system showed improved accuracy for predicting 5-year metastasis (C-index 0.80 vs 0.70) and 10-year prostate cancer-specific mortality (C-index 0.77 vs 0.64) as compared with the original Gleason score [7].

Until truly objective methods of pathological assessment emerge, additional validation of the new grade group system is likely to further support its use moving forward. As Danneman et al. point out, however, we must keep in mind that biopsy, although perhaps our most useful tool, captures only a small fraction of the overall picture.

Jeffrey J. Tosoian* and Jonathan I. Epstein*,,‡ *James Buchanan


Brady Urological Institute and Department of Urology, Department of Pathology, Johns Hopkins University School of Medicine, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA





2 Pierorazio PM, Walsh PC, Partin AW, Epstein JI. Prognostic gleason grade grouping: data based on the modied gleason scoring system. BJU Int 2013; 111: 75360



4 Moch H, Humphrey P, Ulbright T, Reuter V. WHO classication of tumours: pathology and genetics.Tumours of the Urinary and Male Reproductive System. Lyon, France:IARC Press; 2016.


5 Eggener SE, Scardino PT, Walsh PC et al. Predicting 15-year prostate cancer specic mortality after radical prostatectomy. J Urol 2011; 185: 86975


6 Lee MC, Dong F, Stephenson AJ, Jones JS, Magi-Galluzzi C, Klein EAThe Epstein criteria predict for organ-conned but not insignicant disease and a high likelihood of cure at radical prostatectomy. Eur. Urol 2010; 58: 905



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