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

2013 ◽  
Vol 137 (12) ◽  
pp. 1740-1746 ◽  
Author(s):  
M. Scott Lucia ◽  
David G. Bostwick ◽  
Matthew C. Somerville ◽  
Ivy L. Fowler ◽  
Roger S. Rittmaster

Context.—Use of the International Society of Urological Pathology (ISUP) 2005 modified Gleason score may result in higher scores compared with the classic Gleason scoring system. 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 ±1 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 κ 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 = 48) remained constant between reviews, with 3 fewer cases in the placebo group (n = 16) and 3 more in the dutasteride group (n = 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.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 49-49 ◽  
Author(s):  
Michael Donovan ◽  
Phillipp Torkler ◽  
Johan Skog ◽  
Mikkel Noerholm ◽  
Peter Carroll

49 Background: Overdetection and overtreatment of indolent prostate cancer (PCa) remains a significant health issue requiring noninvasive assays to guide the prostate biopsy decision process. We demonstrated that a urine exosome gene expression assay (ExoDx P rostate ( I ntelliScore) (EPI) discriminates GS 7 PCa from GS 6 and benign disease, potentially reducing the number of unnecessary biopsies. The International Society of Urological Pathology (ISUP) proposed a prognostic PCa grading system to accurately reflect the biology of PCa; ISUP separates GS 7 PCa into group 2 (GS 3+4) and group 3 (GS 4+3). We sought to evaluate the performance of the EPI test according to the newly proposed ISUP system. Methods: The 519 patient validation cohort was re-annotated using ISUP and assessed benign (B) +/- ISUP 1 and B+ISUP 1+2 (GS 3+3, GS 3+4) from ISUP 3-5 (GS >= 4+3). We used validated / adjusted cut-points to assess performance with the AUC, sensitivity, specificity and NPV. In addition, we investigated the association of the EPI score with the benign biopsies (BB) and ISUP groups in the combined training and test cohort (n=774). Results: Applying the adjusted cut point (EPI 20) on the 519 ISUP cohort discriminated benign biopsies (BB) + ISUP 1 from >/=ISUP 2, 37% of biopsies avoided, NPV of 90%, equivalent to Gleason grading. Utilizing either the validated (15.6) or adjusted cut points on BB+ISUP 1+ 2 vs. >/=ISUP 3 (dominant pattern 4), 26% vs 37% biopsies avoided, with an improved NPV 98%. In the combined training / test cohort, higher EPI scores were significantly associated with ISUP categories. In this analysis EPI in BB vs. all ISUP groups (p<0.0001); BB+ISUP 1 vs. >/= ISUP2 (p<0.0001) and BB+ISUP 1+2 vs. >/=ISUP3 (p<0.0001); supporting accurate discrimination in high grade PCa. Conclusions: The EPI test is a noninvasive, first-catch non-DRE gene expression assay that accurately discriminates low-grade from high-grade PCa in both ISUP as well as Gleason score based grading systems. The test has the potential to reduce the number of unnecessary biopsies and performs equally well in contemporary approaches to PCa stratification.


2016 ◽  
Vol 140 (10) ◽  
pp. 1140-1152 ◽  
Author(s):  
Oleksandr N. Kryvenko ◽  
Jonathan I. Epstein

Since 1966, when Donald Gleason, MD, first proposed grading prostate cancer based on its histologic architecture, there have been numerous changes in clinical and pathologic practices relating to prostate cancer. Patterns 1 and 2, comprising more than 30% of cases in the original publications by Gleason, are no longer reported on biopsy and are rarely diagnosed on radical prostatectomy. Many of these cases may even have been mimickers of prostate cancer that were described later with the use of contemporary immunohistochemistry. The original Gleason system predated many newly described variants of prostate cancer and our current concept of intraductal carcinoma. Gleason also did not describe how to report prostate cancer on biopsy with multiple cores of cancer or on radical prostatectomy with separate tumor nodules. To address these issues, the International Society of Urological Pathology first made revisions to the grading system in 2005, and subsequently in 2014. Additionally, a new grading system composed of Grade Groups 1 to 5 that was first developed in 2013 at the Johns Hopkins Hospital and subsequently validated in a large multi-institutional and multimodal study was presented at the 2014 International Society of Urological Pathology meeting and accepted both by participating pathologists as well as urologists, oncologists, and radiation therapists. In the present study, we describe updates to the grading of prostate cancer along with the new grading system.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 216-216
Author(s):  
Gian Luigi Petrone ◽  
Francesco Pierconti ◽  
Maurizio Martini ◽  
Tonia Cenci ◽  
Luigi Maria Larocca

216 Background: In the 2005 International Society of Urological Pathology (ISUP) Consensus Conference, a modified Gleason grading system for prostate cancer was proposed. (Epstein JI et al. Am J Surg Pathol 2005; 29:1228-1242) Afterwards an interobserver study among experts in genitourinary pathology proposed some modifications and refinements to the 2005 ISUP modified grading system concerning the cribriform pattern carcinoma that it should never be diagnosed as Gleason pattern 3, assigning Gleason pattern 4 to cribriform glands (Latour M et al. Am J Surg Pathol 2008; 32: 1532-1539; Epstein J I Journal of Urology 2010: 183:433-440). Methods: The study population consisted of 80 patients undergoing biopsies at the Institute of Urology of our hospital, between February 2012 and January 2013 stratified into 3 different categories on the basis of histologic pattern: 1) 20 patients with classical and modified Gleason score 3+3 = 6; 2) 30 patients with classical Gleason score 3+3 = 6 upgraded to Gleason score 7 according to the ISUP modified grading system; and 3) 30 patients with classical and modified Gleason score 3+4 = 7. We evaluate the immunohistochemical protein expression of the suppressor of cytokine signaling (SOCS) proteins 3 (SOCS3) in these three different group of prostatic cancer biopsies. Results: We found that the SOCS3 pattern staining negative (-) or with SOCS3 negative staining with weak intensity staining in less than 50% of neoplastic glands (+/-) increases progressively in concomitance with the rise of Gleason score and SOCS3 positivity (+), correlates with classical or modified Gleason score 6 (P = 0,0004 Fisher’s exact tests) and with classical Gleason score 3+3 = 6 upgraded to Gleason score 7 (P = 0,0010 Fisher’s exact tests). Conclusions: In conclusion our data seem to support from a molecular point of view the modified criteria by 2005 International Society of Urological Pathology (ISUP) Consensus Conference as well as the hypothesis that the diagnosis of Gleason cribriform pattern 3 virtually does not exist and cribriform glands-regardless of their size-are nearly always considered pattern 4.


2007 ◽  
Vol 33 (5) ◽  
pp. 639-651 ◽  
Author(s):  
Sergio G. Veloso ◽  
Mario F. Lima ◽  
Paulo G. Salles ◽  
Cynthia K. Berenstein ◽  
Joao D. Scalon ◽  
...  

2009 ◽  
Vol 27 (21) ◽  
pp. 3459-3464 ◽  
Author(s):  
Jennifer R. Stark ◽  
Sven Perner ◽  
Meir J. Stampfer ◽  
Jennifer A. Sinnott ◽  
Stephen Finn ◽  
...  

Purpose Gleason grading is an important predictor of prostate cancer (PCa) outcomes. Studies using surrogate PCa end points suggest outcomes for Gleason score (GS) 7 cancers vary according to the predominance of pattern 4. These studies have influenced clinical practice, but it is unclear if rates of PCa mortality differ for 3 + 4 and 4 + 3 tumors. Using PCa mortality as the primary end point, we compared outcomes in Gleason 3 + 4 and 4 + 3 cancers, and the predictive ability of GS from a standardized review versus original scoring. Patients and Methods Three study pathologists conducted a blinded standardized review of 693 prostatectomy and 119 biopsy specimens to assign primary and secondary Gleason patterns. Tumor specimens were from PCa patients diagnosed between 1984 and 2004 from the Physicians' Health Study and Health Professionals Follow-Up Study. Lethal PCa (n = 53) was defined as development of bony metastases or PCa death. Hazard ratios (HR) were estimated according to original GS and standardized GS. We compared the discrimination of standardized and original grading with C-statistics from models of 10-year survival. Results For prostatectomy specimens, 4 + 3 cancers were associated with a three-fold increase in lethal PCa compared with 3 + 4 cancers (95% CI, 1.1 to 8.6). The discrimination of models of standardized scores from prostatectomy (C-statistic, 0.86) and biopsy (C-statistic, 0.85) were improved compared to models of original scores (prostatectomy C-statistic, 0.82; biopsy C-statistic, 0.72). Conclusion Ignoring the predominance of Gleason pattern 4 in GS 7 cancers may conceal important prognostic information. A standardized review of GS can improve prediction of PCa survival.


2018 ◽  
Vol 73 (5) ◽  
pp. 684-686 ◽  
Author(s):  
Rodolfo Montironi ◽  
Liang Cheng ◽  
Marina Scarpelli ◽  
Antonio Lopez-Beltran

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 537 ◽  
Author(s):  
Renuka Sriram ◽  
Mark Van Criekinge ◽  
Justin DeLos Santos ◽  
Fayyaz Ahamed ◽  
Hecong Qin ◽  
...  

Non-invasive assessment of the biological aggressiveness of prostate cancer (PCa) is needed for men with localized disease. Hyperpolarized (HP) 13C magnetic resonance (MR) spectroscopy is a powerful approach to image metabolism, specifically the conversion of HP [1-13C]pyruvate to [1-13C]lactate, catalyzed by lactate dehydrogenase (LDH). Significant increase in tumor lactate was measured in high-grade PCa relative to benign and low-grade cancer, suggesting that HP 13C MR could distinguish low-risk (Gleason score ≤3 + 4) from high-risk (Gleason score ≥4 + 3) PCa. To test this and the ability of HP 13C MR to detect these metabolic changes, we cultured prostate tissues in an MR-compatible bioreactor under continuous perfusion. 31P spectra demonstrated good viability and dynamic HP 13C-pyruvate MR demonstrated that high-grade PCa had significantly increased lactate efflux compared to low-grade PCa and benign prostate tissue. These metabolic differences are attributed to significantly increased LDHA expression and LDH activity, as well as significantly increased monocarboxylate transporter 4 (MCT4) expression in high- versus low- grade PCa. Moreover, lactate efflux, LDH activity, and MCT4 expression were not different between low-grade PCa and benign prostate tissues, indicating that these metabolic alterations are specific for high-grade disease. These distinctive metabolic alterations can be used to differentiate high-grade PCa from low-grade PCa and benign prostate tissues using clinically translatable HP [1-13C]pyruvate MR.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Saeed Alqahtani ◽  
Cheng Wei ◽  
Yilong Zhang ◽  
Magdalena Szewczyk-Bieda ◽  
Jennifer Wilson ◽  
...  

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