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Originally published as JCO Early Release 10.1200/JCO.2008.20.4669 on May 11 2009 © 2009 American Society of Clinical Oncology.
Gleason Score and Lethal Prostate Cancer: Does 3 + 4 = 4 + 3?
From the Departments of Epidemiology, Biostatistics, and Nutrition, Harvard School of Public Health; Channing Laboratory and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital; Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA; and the Department of Pathology and Laboratory Medicine, Weill Medical College, Cornell University, New York, NY. Corresponding author: Jennifer R. Stark, ScD, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115; e-mail: stark{at}hsph.harvard.edu. 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. M.A.R. and L.A.M. contributed equally to this article. Supported by Grants No. 5R01CA058684-13 and 5R01CA042182-20 from the National Cancer Institute; Grant No. W81XWH-05-1-0562 from the Department of Defense; and Grant No. T32 CA009001-32 from the National Research Service Award Training Program in Cancer Epidemiology and a Dana-Farber/Harvard Cancer Center SPORE Career Development Award (J.R.S.). The Physicians Health Study is supported by Grants No. CA34944, CA40360, and CA097193 from the National Cancer Institute and Grants No. HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute. Presented in part in abstract format at the Annual Meeting of the American Association for Cancer Research, April 12-16, 2008, San Diego, CA. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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