Does Gleason Grade Progress over Time?
Meir J Stampfer, Kathryn Penney, Jennifer Sinnott, Richard Flavin, Jennifer Stark, Stephen Finn, Edward Giovannucci, Howard Sesso, Massimo Loda, Lorelei Mucci, Michelangelo Fiorentino. Dana Farber/Harvard Cancer Center, Boston, MA
Background: Pathologists have speculated on whether prostate cancers arise as well differentiated tumors, and then progress, or whether grade is an early and unchanging feature. This cannot readily be addressed through repeated biopsy, due to selection of subjects and heterogeneity of tumor within the prostate. However, the advent of PSA screening affords the opportunity to assess this issue on a population level. PSA screening provides a lead time of 10-12 years, and widespread screening has dramatically reduced the number and proportion of tumors diagnosed at advanced stage. If Gleason grade progresses, one would expect a similar reduction in high grade tumors.
Design: We studied 1,077 US participants in the Physician's Health Study and the Health Professionals Follow-up Study, diagnosed between 1982 and 2005, and treated with prostatectomy. Using the ISUP 2005 revised criteria, we re-reviewed H&E slides to assign major and minor Gleason grades, blinded to clinical outcome, to avoid the problem of the shift in Gleason scoring over the past several decades. We assessed clinical stage at diagnosis from medical records. We compared the distribution of grade and stage across four time categories, to span the pre- and PSA eras.
Results: As expected, the proportion of tumors diagnosed at advanced stage dropped dramatically. In the earliest period (1982-1992, pre-PSA) 19.6% were Stage T3 or higher. This proportion decreased steadily until the last period (2000-2005), with only 2.3% of tumors Stage T3, and none Stage T4 or M1. In contrast, the proportion of Gleason grade 8-10 decreased only modestly, from 21.1% in the first period to 14.3%.
Conclusions: The dramatic shift in stage at diagnosis after introduction of PSA screening was accompanied by only a modest shift to lower Gleason scores. On a population basis, these finding suggest that Gleason grade may be established early in the pathogenesis of prostate tumors. This finding has implications for our understanding of prognosis and of tumor progression.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 67, Wednesday Morning