Integrating Tertiary Gleason 5 Patterns into Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens

Abstract

Background: Presence of small (tertiary) Gleason 5 pattern is linked to a higher risk of biochemical recurrence in prostate cancer. It is unclear, however, how to integrate small Gleason 5 elements into clinically relevant Gleason grade groups.

Objective: To analyze the prognostic impact of Gleason 5 patterns in prostate cancer and to develop a method for integrating tertiary Gleason 5 patterns into a quantitative Gleason grading system.

Design, setting, and participants: Prostatectomy specimens from 13 261 consecutive patients and of 3295 matched preoperative biopsies were available. Percentages of Gleason 3, 4, and 5 had been recorded for each cancer. Outcome measurements and statistical analysis: RESULTS AND LIMITATIONS: Our data demonstrate that minimal Gleason 5 areas have strong prognostic impact in Gleason 7 carcinomas, while further expansion of the Gleason 5 pattern population has less impact. We thus defined an integrated quantitative Gleason score (IQ-Gleason) by adding a lump score of 10 to the percentage of unfavorable Gleason pattern (Gleason 4/5) if any Gleason 5 was present and by adding another 7.5 points in case of a Gleason 5 fraction >20%. There was a continuous increase of the risk of prostate-specific antigen recurrence with increasing IQ-Gleason. This was also true for subgroups with identical Cancer of the Prostate Risk Assessment Postsurgical scores (p<0.0001) or Gleason grade groups (p<0.0001).

Conclusions: The IQ-Gleason represents a simple and efficient approach for combining both quantitative Gleason grading and tertiary Gleason grades in one highly prognostic numerical variable.

Patient summary: Prostatectomy specimens (13 261) were analyzed to estimate the relevance of small Gleason 5 elements in prostate cancers. Even the smallest Gleason 5 areas markedly increased the risk of prostate-specific antigen recurrence after surgery. Larger fractions of Gleason 5 patterns had less further impact on prognosis. Based on this, a numerical Gleason score (integrated quantitative Gleason score) was defined by the percentages of Gleason 4 and 5 patterns, enabling a refined estimate of patient prognosis.

Keywords: Gleason score; Prognosis; Prostate cancer; Quantitative Gleason grade.