Serum levels of prostate specific antigen, free PSA, [-2]proPSA, fPSA/tPSA ratio, Prostate Health Index, and glycosylation patterns of free PSA in patients with benign prostatic hyperplasia pharmacotherapy

Prostate. 2025 Jan;85(1):65-72. doi: 10.1002/pros.24801. Epub 2024 Sep 27.

Abstract

Background: The medication used to treat benign prostate hyperplasia (BPH), a common condition in men over 50 years of age, can alter the levels of biomarkers used in prostate cancer detection. Commonly used medications for BPH include alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and muscarinic antagonists. We studied the impact of these drugs on total prostate-specific antigen (tPSA), free PSA (fPSA), [-2]proPSA, fPSA/tPSA ratio, and the Prostate Health Index (PHI), as well as novel potential biomarkers in the form of glycan composition of fPSA.

Patients and methods: Serum samples were collected from 564 males with BPH, with a mean age of 68.5 years. The samples were used to measure levels of tPSA, fPSA, and [-2]proPSA. The fPSA/tPSA and PHI were then calculated. The glycan composition of fPSA was analyzed using lectin-based glycoprofiling. Pharmacotherapy data was collected from the patients' medical records.

Results: Alpha-blocker monotherapy was associated with higher fPSA and fPSA/tPSA ratio, and decreased PHI. Levels of tPSA were not impacted. Alpha-blocker and 5-ARI dual therapy was associated with reduced levels of fPSA, [-2]proPSA, and PHI. Therapy combining alpha-blockers and antimuscarinic agents did not significantly influence biomarker levels apart from an increase in a Maackia amurensis lectin-recognized glycan originating in fPSA.

Conclusion: BPH pharmacotherapy notably affects prostate cancer biomarkers. Recognizing the impact of pharmacotherapy is crucial for achieving an accurate diagnosis of prostate cancer and for planning treatment.

Keywords: 5‐alpha reductase inhibitors; PSA; alpha‐blockers; antimuscarinic agents; benign prostate hyperplasia; prostate cancer.

MeSH terms

  • 5-alpha Reductase Inhibitors / therapeutic use
  • Adrenergic alpha-Antagonists / therapeutic use
  • Aged
  • Aged, 80 and over
  • Glycosylation
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists* / therapeutic use
  • Prostate / metabolism
  • Prostate / pathology
  • Prostate-Specific Antigen* / blood
  • Prostatic Hyperplasia* / blood
  • Prostatic Hyperplasia* / drug therapy
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy

Substances

  • Prostate-Specific Antigen
  • Muscarinic Antagonists
  • Adrenergic alpha-Antagonists
  • 5-alpha Reductase Inhibitors