PATHOLOGY

The combined percentage of Gleason 4 and 5 is the best predictor of cancer progression after radical prostatectomy
Cheng L, Koch MO, Daggy J
Indiana University School of Medicine, Indianapolis, Indianapolis, USA
Mod Pathol. 2004; 17 (suppl.1): 145A

• Background: Clinical outcome is variable in prostate cancer patients treated by radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biological aggressiveness of prostate cancer. We evaluate the significance of relative proportion of high grade cancer (Gleason pattern 4 and/or 5) in predicting cancer progression in prostate cancer patients treated by radical prostatectomy.
• Design: Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All the data were collected prospectively.
• Results: The primary Gleason grade, secondary Gleason grade, Gleason score sum, the presence of Gleason grade 4, % of Gleason grade 4, the presence of Gleason grade 5, % of Gleason grade 5, and the combined % of Gleason grade 4 and 5 were all predictive of PSA recurrence (all P value <0.001). However, based on the Likelihood Ratio Test statistic the combined % of Gleason grade 4/5 is the best predictor of PSA recurrence. In a multivariate analysis that included the combined % of Gleason grade 4/5, Gleason score sum, tumor stage (T2 vs. T3), and surgical margins, only the combined % of Gleason grade 4/5 (P = 0.005) and surgical margins (P=0.01) were independent predictors of PSA recurrence.
• Conclusions: The combined percentage of Gleason 4 and 5 is one of the most powerful predictors of patient outcome. We recommend that the combined percentage of Gleason 4 and 5 be evaluated in radical prostatectomy specimens.
  
  
• Editorial Comment
  As a measure of intrinsic biologic aggressiveness, Gleason grading may be enhanced by both structural (morphologic and morphometric) and functional means (by using gene expression profiling, for example). One proposed morphologic approach is quantitation of the amount of high-grade (percentage Gleason grade 4/5) carcinoma.
  This paper clearly showed that the combined percentage of Gleason 4 and 5 is one of the most powerful predictors of patient outcome. We have recently evaluated in our Department 88 patients submitted to radical prostatectomy with a follow-up period of 12 to 63 (median = 26 months).Our data showed that comparing Gleason score (< 7 vs. = 7) and Gleason predominant grade (< 4 vs. 4/5) in the surgical specimen, only Gleason grade 4/5 was a statistically significant predictor of progression (recurrence and/or metastases) following radical prostatectomy.
  Urologists should differentiate high-grade Gleason score 4 + 3 = 7 from 3 + 4 = 7. They have different biological significance. Pathologists should always report grade 4/5 in radical prostatectomy specimens even if it corresponds to a tertiary grade.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil