Plasma Steroid Trajectories From Day‐of‐Surgery Baseline After Robot‐Assisted Radical Prostatectomy for Prostate Cancer

ABSTRACT Background Circulating steroid trajectories after robot‐assisted radical prostatectomy are poorly characterized from the day‐of‐surgery baseline, and relevant biology extends beyond testosterone and dihydrotestosterone to adrenal‐derived 11‐oxygenated androgens and steroid conjugate turnover. This study aimed to characterize 3‐ and 6‐month plasma steroid differences from a day‐of‐surgery baseline and evaluate baseline steroid biomarkers for adverse pathology, upgrading, and early detectable prostate‐specific antigen (PSA). Methods This prospective, single‐center cohort included 173 men undergoing robot‐assisted radical prostatectomy. Fasting plasma was sampled before premedication on the morning of surgery and at 3 and 6 months. A 34‐analyte steroid panel, including conjugated analytes, was quantified using liquid chromatography–tandem mass spectrometry. Longitudinal differences were analyzed using mixed‐effects models. Baseline screening used logistic regression with false discovery rate correction and adjusted models for retained signals. Results For most analytes, 168–170 baseline samples and 131/108 samples at 3/6 months were available. Relative to baseline, 11‐ketotestosterone increased at 3 and 6 months (fold changes 1.36 [95% CI 1.24–1.49] and 1.25 [1.13–1.38]), corticosterone decreased (0.61 [0.52–0.70] and 0.59 [0.51–0.69]), cortisol decreased (0.91 [0.84–1.00] and 0.86 [0.78–0.94]), and conjugated corticosterone/corticosterone increased (1.96 [1.57–2.45] and 2.41 [1.90–3.06]), all p < 0.04. At 6 months, neither testosterone (fold change 0.88; 95% CI 0.75–1.03) nor dihydrotestosterone (0.90; 0.79–1.04) differed significantly from the day‐of‐surgery baseline. The conjugated/unconjugated estrone ratio (E1C/E1) was the only retained baseline adverse‐pathology signal, with inverse adjusted associations for pT3a/b disease (OR 0.61; 95% CI 0.41–0.90; p = 0.013) and composite adverse pathology (OR 0.53; 95% CI 0.36–0.78; p = 0.001). No biomarker remained significant for upgrading or detectable PSA. Conclusions Relative to the day‐of‐surgery baseline, longitudinal differences involve corticosteroid‐related and 11‐oxygenated analytes, but their mechanisms remain unresolved. These data define postoperative steroid trajectories from a day‐of‐surgery baseline without establishing prostatectomy‐specific endocrine effects. Baseline E1C/E1 warrants external validation as a hypothesis‐generating marker of adverse pathology.