Presentation Authors: Andrew Gabrielson*, Amit Reddy, Laith Alzweri, Andrew Sholl, Jonathan Silberstein, Wayne Hellstrom, New Orleans, LA
Introduction: Male hypogonadism promotes a pro-inflammatory state in the prostate that may incite a prostatitis-like syndrome and lower urinary tract symptoms (LUTS); yet, recent evidence suggests that high levels of total testosterone (TT) may also induce prostate inflammation. We aim to elucidate the relationship between TT and prostate lymphocytic infiltration.
Methods: Prostates from treatment-naive patients undergoing radical prostatectomy (RP) were retrospectively acquired, matched for Gleason sum, age, and TNM stage, and stratified by pre-RP TT: < 293 ng/dL (hypogonadal), 293-464 ng/dL (low eugonadal), >464 ng/dL (high eugonadal). Analysis of infiltrating lymphocyte density (cells/mm2) was performed (ImageJ), and a clinical pathologist assessed immune cell types (CD4+, CD8+, CD68+).
Results: Twenty-three RP specimens (9 hypogonadal, 6 low eugonadal, 8 high eugonadal) were included. When comparing tumor infiltrating lymphocyte densities, there were significant differences between all three groups on ANOVA (393 cells/mm2, 27 cells/mm2, and 113 cells/mm2, respectively, P = 0.0356). In benign tissue, both hypogonadal and high eugonadal arms demonstrated significantly higher lymphocyte densities than the low eugonadal arm (310 cells/mm2, 266 cells/mm2, and 9 cells/mm2, respectively), but there was no difference between the hypogonadal and high eugonadal arms. There was a U-shaped relationship between infiltrating lymphocytes and TT levels within both tumor and benign tissue (Fig.). ANOVA revealed no significant association between lymphocyte densities and comorbid conditions. The predominant pattern of infiltrating CD4+, CD8+, and CD68+ cells was focal clustering; few specimens demonstrated a diffuse inflammatory pattern.
Conclusions: This small observational study demonstrated a U-shaped relationship between TT and the degree of lymphocyte infiltration within prostate tumor and benign tissue. This is consistent with published results demonstrating that rates of prostatitis may be minimized in patients with TT between 293-464 ng/dL. It is thus conceivable that this range may represent an optimal TT target for testosterone replacement therapy such that prostate inflammation, prostatitis-like symptoms, and LUTS are reduced.
Source of Funding: American Urological Association Herber Brendler, MD Fund Medical Student Research Fellowship, Alpha Omega Alpha Carolyn L. Kuckein Research Fellowship.