Urinary Amino Acid Profiling as a Non-invasive Diagnostic and Risk Stratification Tool in Prostate Cancer

Prostate cancer (PCa) is a leading malignancy in men worldwide. Despite its routine use, PSA testing lacks specificity and often results in unnecessary biopsies, especially in men with borderline PSA values. Urinary metabolomic profiling may offer a fully non-invasive approach to detect tumor-related metabolic alterations. Amino acids are of interest due to their roles in cancer metabolism, proliferation, and redox regulation. Building on our previous pilot study, we assessed whether urinary amino acid concentrations can differentiate PCa from benign cases, identify high-risk disease, and provide diagnostic information independent of prostate volume or prior prostate manipulation.

First-morning urine samples without prior prostate manipulation were collected from 90 men: 60 with histologically confirmed PCa and 30 healthy controls. Total urinary amino acids were quantified using high-performance liquid chromatography with fluorescence detection and normalized to creatinine. The primary analysis compared amino acid concentrations between PCa and controls. Secondary analyses assessed associations with PSA, prostate volume, lymph-node status, surgical margins, postoperative PSA detectability, and preoperative risk category.

Significant alterations were observed in glutamate+glutamine (p=0.005), arginine (p=0.030), leucine (p<0.001), and methionine (p=0.013). Leucine had the highest discriminatory performance (AUC=0.79). Combining PSA with these amino acids significantly improved diagnostic accuracy (p=0.024). Serine was lower in node-positive patients (p=0.046; AUC=0.81), and histidine was elevated in high-risk disease (p=0.039; AUC=0.73). Amino acid concentrations were independent of prostate volume and PSA.

Urinary amino acid profiling shows promise as a non-invasive adjunct to PSA testing. This cohort validates our prior pilot data. Specific amino acids may improve diagnostic specificity, particularly in men with borderline PSA. The approach without prior prostate manipulation, patient-friendly sampling enhances outpatient applicability. Larger multi-center validation is warranted to confirm diagnostic potential and assess integration with PSA testing to reduce unnecessary biopsies.