Blood Prostate-specific Antigen by Volume of Benign, Gleason Pattern 3 and 4 Prostate Tissue

To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer.

The cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. R², a measure of explained variation, was calculated using a multivariable model.

Estimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). R² decreased only slightly when removing age (0.006/0.018), volume of benign tissue (0.051/0.054) or GP3 (0.014/0.023) from the model. When GP4 was removed, R² decreased 0.051/0.310. PSA density (PSA divided by prostate volume) was associated with volume of GP4 but not GP3, after adjustment for benign volume.

Gleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4.