Urinary and cellular volatile organic compounds as biomarkers for urological cancers: a systematic review of...

Volatile organic compounds (VOCs) in human biofluids are promising non-invasive cancer biomarkers. However, their potential in urological cancers, including prostate, bladder, and kidney cancers is less explored, and the relationships between urinary and cellular VOC profiles across these cancer types remain unclear.

This systematic review aimed to evaluate gas chromatography-mass spectrometry (GC-MS)-based untargeted volatolomics studies in urological cancers to investigate cancer-specific, cross-cancer, and cross-matrix (urine vs. cell culture media) VOC biomarkers, while assessing methodological factors influencing biomarker discovery.

Published urinary and cellular VOC studies in prostate, bladder, and kidney cancers were systematically reviewed. VOC biomarkers, direction of change, diagnostic performance, sampling methods, analytical platforms, compound-identification strategies, and statistical approaches were extracted and compared across cancer types and sample matrices.

A total of 12 urinary prostate, 9 urinary bladder, 5 urinary renal, and 3 cellular VOC studies were identified. Prostate cancer profiles were mainly characterized by decreased organic acids and alcohols, whereas bladder and renal cancers more frequently showed elevated ketones and aldehydes. Several VOCs, including 2-butanone, 2-heptanone, hexanal and phenol, were identified across multiple cancer types. Cellular studies showed consistent directional changes for six VOCs, and cross-matrix analysis identified 28 shared VOCs, seven of which showed aligned trends in urine and cell models. These findings suggest that VOCs reflect both unique and shared metabolic alterations in urological cancers and may serve as useful diagnostic biomarker candidates.

This review integrates urinary and cellular VOC data across major urological cancers and identifies unique, recurrent, and cross-matrix VOCs that warrant further mechanistic and clinical validation. Although methodological heterogeneity remains a challenge, VOC-based approaches have generally shown good sensitivity and specificity for distinguishing malignant from healthy controls. With improved and standardized analytical methods, VOC volatolomics may support the future development of non-invasive and accurate diagnostics for urological cancers.