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Contribution of Gleason Pattern 4 Prostate Tissue to Blood PSA Levels
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersOBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Additional Info
Blood Prostate-specific Antigen by Volume of Benign, Gleason Pattern 3 and 4 Prostate Tissue
Urology 2022 Dec 01;170(122022)154-160, C Andolfi, AJ Vickers, MR Cooperberg, PR Carroll, JE Cowan, GP Paner, BT Helfand, SL Liauw, SE EggenerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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This elegant study by the groups from the University of Chicago and the University of California San Francisco with statistical collaboration from Vickers from the Memorial Sloan Kettering Cancer Center studied over 2000 radical prostatectomy specimens and found that Gleason pattern 4 was a much larger contributor to serum PSA levels than Gleason pattern 3 or benign tissue. Although well controlled for, what struck me was the difference in the median tumor volumes between the Chicago cohort (4.8 cc) and the San Francisco cohort (1.6 cc), reflecting a different patient population. Conversely, there was no statistically significant difference in the serum PSA levels contributed by the volume of Gleason pattern 3 and benign prostate. The absolute volume of Gleason pattern 4 was clearly the strongest predictor of an elevated PSA level, and Gleason pattern 4, but not 3, predicted the PSA density. The take-home message for prostate screening, according to the authors, is that Gleason pattern 3 alone does not raise PSA levels considerably more than benign tissue, but Gleason pattern 4 is the main driver of an elevated PSA level. I wish that the authors had also performed a sub-analysis by race/ethnicity. In the past, our group found that African American men had higher serum PSA levels due to higher within-stage group whole mount–derived tumor volumes compared with White men.1 This led to age- and race/ethnicity-optimized PSA screening guidelines.2 It would be very interesting to determine if the specific volume of Gleason pattern 4 determines a difference in serum PSA levels by race in the cohorts studied here.
References