Biological Determinants of Cancer Progression in Men With Prostate Cancer

Stamey, Thomas A. MD
McNeal, John E. MD
Yemoto, Cheryl M.
Sigal, Bronislava M. PhD
Johnstone, Iain M. PhD

Author Affiliations: Department of Urology (Stamey and McNeal and Ms Yemoto), School of Medicine, and the Department of Statistics (Sigal and Johnstone), Stanford University, Stanford, Calif.

JAMA: The Journal of the American Medical Association 281(15):p 1395-1400, April 21, 1999.

Context

The recent increase in ability to diagnose prostatic adenocarcinoma has created a dilemma for treatment decisions.

Objective

To determine whether prostate cancer progression is associated with a modified version of the Gleason grading system together with selected morphologic and clinical variables.

Design

Retrospective analysis of a cohort of patients with peripheral zone prostate cancers who underwent surgery between August 1983 and July 1992.

Setting

University hospital.

Patients

Radical prostatectomy specimens from 379 men treated only by surgical excision were prospectively studied for 8 morphologic variables using previously standardized techniques. Variables were percentage of each cancer occupied by Gleason grade 4/5 (% Gleason grade 4/5, the Stanford modified Gleason scale), cancer volume, vascular invasion, lymph node involvement, seminal vesicle invasion, capsular penetration, positive surgical margin, prostate weight, and preoperative prostate-specific antigen (PSA) level.

Main Outcome Measure

Biochemical progression of prostate cancer as indicated by serum PSA level of 0.07 ng/mL and increasing.

Results

Cancer grade expressed as % Gleason grade 4/5 and cancer volume were highly predictive of disease progression. In a Cox proportional hazards model that included % Gleason grade 4/5, the traditional Gleason score was not an independent predictor of treatment failure. Positive lymph node findings and intraprostatic vascular invasion were the only other variables that remained significant at the.01 level.

Conclusion

The % Gleason grade 4/5, cancer volume, positive lymph node findings, and intraprostatic vascular invasion were independently associated with prostate cancer progression, defined by an increasing PSA level. Techniques to accurately measure cancer volume and % Gleason grade 4/5 are needed to better predict which patient will experience cancer progression. The commonly accepted predictors of progression-capsular penetration and positive surgical margins-were not independently predictive of failure after radical prostatectomy.

JAMA.1999;281:1395-1400