A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score

Abstract

Background: Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group.

Objective: To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data.

Design, setting, and participants: Between 2005 and 2014, 20,845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions.

Outcome measurements and statistical analysis: Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores.

Results and limitations: In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death.

Conclusions: The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.

Patient summary: We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.

Keywords: Gleason grade; Gleason score.

Fig. 1

Recurrence-free progression following radical prostatectomy stratified by prostatectomy grade. Green line: Gleason score 6, grade group 1. Orange line: Gleason score 3 + 4, grade group 2. Dark blue line: Gleason score 4 + 3, grade group 3. Brown line: Gleason score 8, grade group 4. Gray line: Gleason score ≥9, grade group 5. RFP = recurrence-free progression.

Fig. 2

Recurrence-free progression following radical prostatectomy stratified by pre-prostatectomy biopsy grade. Green line: Gleason score 6, grade group 1. Orange line: Gleason score 3 + 4, grade group 2. Dark blue line: Gleason score 4 + 3, grade group 3. Brown line: Gleason score 8, grade group 4. Gray line: Gleason score ≥9, grade group 5. RFP = recurrence-free progression.

Fig. 3

Recurrence-free progression following radiation stratified by pre–radiation therapy biopsy grade (entire cohort). Green line: Gleason score 6, grade group 1. Orange line: Gleason score 3 + 4, grade group 2. Dark blue line: Gleason score 4 + 3, grade group 3. Brown line: Gleason score 8, grade group 4. Gray line: Gleason score ≥9, grade group 5. RFP = recurrence-free progression.

Fig. 4

Recurrence-free progression following radiation stratified by pre–radiation therapy biopsy grade (no hormone therapy cohort). Green line: Gleason score 6, grade group 1. Orange line: Gleason score 3 + 4, grade group 2. Dark blue line: Gleason score 4 + 3, grade group 3. Brown line: Gleason score 8, grade group 4. Gray line: Gleason score ≥9, grade group 5. RFP = recurrence-free progression.

Fig. 5

Images of cases diagnosed as Gleason score 6 prior to 2005 from Johns Hopkins Hospital, Henry Ford Hospital, University of California San Francisco, or Baylor College of Medicine (modified from Ross et al [17]). (a) Gleason pattern 4 with glomeruloid glands. (b) Gleason pattern 4 with medium-sized rounded cribriform gland. Associated small glands of pattern 3. (c) Gleason pattern 4 with poorly formed and fused glands. (d) Gleason pattern 4 with irregular cribriform gland with adjacent Gleason pattern 3.