Plasma infrared molecular fingerprinting for prostate cancer detection: Prospective evidence for a partially PSA-independent signal.

BACKGROUND

Prostate-specific antigen (PSA) testing has limited specificity, particularly at intermediate concentrations, contributing to diagnostic uncertainty in prostate cancer (PCa). Infrared molecular fingerprinting (IMF) provides a rapid plasma-based readout of systemic biochemical variation and may capture PCa-associated molecular information not fully reflected by PSA.

METHODS

In the prospective Lasers4Life study, plasma from 2024 men was analysed, including 1012 treatment-naïve PCa patients, 752 men with benign prostatic hyperplasia (BPH), and 260 asymptomatic controls. Classification models were evaluated using cross-validation and, for PCa-versus-BPH discrimination, temporally independent held-out testing. Performance was quantified by receiver operating characteristic area under the curve (ROC AUC) and examined across PSA strata, comorbidities, and medications.

RESULTS

IMF discriminated PCa from asymptomatic controls more strongly than from BPH, with cross-validated AUCs of 0.79 ± 0.08 and 0.67 ± 0.04, respectively. In an exploratory age- and PSA-matched subset of men with PSA below 12 ng/mL, comprising 200 PCa and 200 BPH cases, IMF showed higher discrimination than PSA alone, although performance remained modest (AUC 0.63 vs 0.56; p < 1 ×10⁻⁴). Most examined comorbidities and medications did not substantially alter IMF performance, although prostatitis reduced discrimination.

CONCLUSIONS

Plasma IMF detected PCa-associated variation in a pre-treatment diagnostic setting, including information partly independent of PSA. However, discrimination was modest in the clinically relevant PCa-versus-BPH comparison and did not exceed PSA in the overall cohort. These findings support further evaluation of IMF as an adjunctive molecular-profiling approach, requiring independent multicentre validation, clinically significant PCa endpoints, and demonstration of additive value within established diagnostic pathways.