Breath Aldehyde Profiling using PFBHA-GC/MS as a Prostate Cancer Biomarker

BACKGROUND: While PSA screening reduces prostate cancer (PCa) mortality, it is associated with overdiagnosis and unnecessary biopsies. Breathomics presents a painless, repeatable adjunct method, provided that robust volatile biomarkers can be reliably identified. OBJECTIVE: To evaluate whether targeted quantification of 12 biologically plausible aldehydes in end-tidal breath can differentiate histologically confirmed PCa from biopsy-negative or low-PSA control subjects. METHODS: In a prospective exploratory study at Toho University Omori Medical Center (Tokyo, Japan), we enrolled men aged ≥50 years between 1 September 2020 and 31 August 2023. Breath samples, obtained after an overnight fast, were derivatised with O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine and analysed using conventional quadrupole GC/MS. Limits of detection ranged from 0.3 to 1.1 ng. Non-detects were addressed using LOD/2 substitution and Tobit left-censored regression. Group differences were assessed using two-tailed Wilcoxon or Fisher's exact tests (α = 0.05). Ethics approval: M16243 / M20229; informed consent was obtained. RESULTS: Thirty-three men were analysed (PCa = 22; controls = 11). Only formaldehyde and acetaldehyde were quantifiable in ≥85% of samples. Median concentrations did not differ (formaldehyde: 3.09 [2.15-5.35] vs. 5.85 [2.72-7.36] ng , p = 0.181; acetaldehyde: 7.47 [5.36-11.73] vs. 7.80 [6.70-14.32] ng, p = 0.456). The exploratory formaldehyde-to-acetaldehyde ratio was likewise non-discriminatory (p = 0.87). The remaining ten aldehydes showed detection rates ≤45.5% and no significant group differences in Tobit modelling. CONCLUSIONS: Single-compound aldehyde profiling with PFBHA-GC/MS failed to differentiate PCa from controls, primarily due to low analyte detection rates and minimal between-group contrasts. Enhanced-sensitivity platforms (e.g., GC×GC-HRMS or MEMS-based pre-concentrators) and multi-component VOC signatures coupled with rigorous control of smoking and ambient confounders are needed before breath testing can contribute meaningfully to prostate cancer screening.