Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3?

Area of Science:

• Oncology
• Pathology
• Cancer Research

Background:

• Gleason grading is a critical prognostic factor for prostate cancer (PCa) outcomes.
• Existing research suggests varying outcomes for Gleason score (GS) 7 based on pattern predominance, influencing clinical practice.
• However, direct comparisons of PCa mortality rates for Gleason 3+4 versus 4+3 tumors are limited.

Purpose of the Study:

• To compare prostate cancer (PCa) mortality rates between Gleason 3+4 and 4+3 tumors.
• To evaluate the predictive accuracy of standardized Gleason grading versus original scoring for PCa outcomes.
• To determine if pattern predominance in GS 7 cancers impacts PCa mortality.

Main Methods:

• A blinded, standardized review of 693 prostatectomy and 119 biopsy specimens by three pathologists.
• Assignment of primary and secondary Gleason patterns.
• Analysis of lethal PCa events (metastases or death) in patients diagnosed between 1984-2004 from the Physicians' Health Study and Health Professionals Follow-Up Study.
• Estimation of hazard ratios (HR) and comparison of model discrimination (C-statistics) for original versus standardized GS.

Main Results:

• Prostatectomy specimens with 4+3 Gleason patterns showed a three-fold increased risk of lethal PCa compared to 3+4 patterns (HR 1.1-8.6).
• Standardized Gleason grading improved the prediction of PCa survival for both prostatectomy (C-statistic 0.86) and biopsy (C-statistic 0.85) specimens.
• Improved discrimination was noted compared to original scores (prostatectomy C-statistic 0.82; biopsy C-statistic 0.72).

Conclusions:

• The predominance of Gleason pattern 4 in Gleason score 7 prostate cancer (PCa) contains crucial prognostic information.
• Ignoring pattern predominance in GS 7 may underestimate PCa mortality risk.
• A standardized review process for Gleason grading enhances the prediction of prostate cancer survival.