Gleason Grade Progression Is Uncommon
Penney KL, Stampfer MJ, Jahn JL, Sinnott JA, Flavin R, Rider JR, Finn S, Giovannucci E, Sesso HD, Loda M, Mucci LA, Fiorentino M. Cancer Res. 2013 Aug 15;73(16):5163-5168.


Authors' Affiliations: Departments of Epidemiology, Nutrition, and Biostatistics, Harvard School of Public Health; Channing Division of Network Medicine, Department of Medicine; Departments of Preventive Medicine and Pathology, Brigham and Women's Hospital and Harvard Medical School; Department of Pathology, Dana-Farber Cancer Institute, Boston; The Broad Institute, Cambridge, Massachusetts; Department of Histopathology Research, Trinity College, Dublin, Ireland; and Pathology Unit, Addarii Institute of Oncology, University of Bologna, Italy.


Gleason grade is universally used for pathologic scoring of the differentiation of prostate cancer. However, it is unknown whether prostate tumors arise well differentiated and then progress to less differentiated forms or if Gleason grade is an early and largely unchanging feature. Prostate-specific antigen (PSA) screening has reduced the proportion of tumors diagnosed at advanced stage, which allows assessment of this question on a population level. If Gleason grade progresses as stage does, one would expect a similar reduction in high-grade tumors. We studied 1,207 Physicians' Health Study and Health Professionals Follow-up Study participants diagnosed with prostate cancer from 1982 to 2004 and treated with prostatectomy. We compared the distribution of grade and clinical stage across the pre-PSA and PSA screening eras. We re-reviewed grade using the ISUP 2005 revised criteria. The proportion of advanced stage tumors dropped more than six-fold, from the earliest period (12/1982-1/1993), 19.9% stage ≥T3, to the latest (5/2000-12/2004), 3% stage T3, none T4. The proportion of Gleason score ≥8 decreased substantially less, from 25.3% to 17.6%. A significant interaction between stage and diagnosis date predicting grade (P = 0.04) suggests that the relationship between grade and stage varies by time period. As the dramatic shift in stage since the introduction of PSA screening was accompanied by a more modest shift in Gleason grade, these findings suggest that grade may be established early in tumor pathogenesis. This has implications for the understanding of tumor progression and prognosis, and may help patients diagnosed with lower grade disease feel more comfortable choosing active surveillance.