Integrating anamnestic and lifestyle data with sphingolipids levels for risk-based prostate cancer screening
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Background
In the new era of risk-based prostate cancer (PCa) screening, stratifying men by their individual risk is crucial. Our study aims to integrate anamnestic, life-style and molecular data to minimize unnecessary second-level investigations (SLI) and improve detection of clinically significant PCa (ISUP>1).
Methods
Since 2021, within the DP3 study, we collected plasma samples, recent clinical history, familiarity for cancer, and life-style information from: 421 men who underwent PSA testing and digital rectal examination (longitudinal sampling every 6 months), 421 men with suspected PCa, before diagnostic biopsy and 62 men with PCa diagnosis, before radical prostatectomy. Fifty sphingolipids were tested in the plasma of 393 men by targeted lipidomics. Univariable logistic regression analysis was applied to identify the variables associated with PCa. Multivariable penalized logistic regression analysis with 10-fold cross validation was run on different subgroups of the total cohort to build each time 10 models on 9/10 of the samples and assess their performance on the 10 test sets.
Results
PSA levels, age, cardiovascular diseases (CVD), number of medications, hypertension, sedentariness, and three sphingolipids (Gb3.24, Cer.20, Cer.24.1) showed a significant association with clinically significant PCa in univariable analysis of the entire cohort. Penalized logistic regression modelling consistently selected hypertension, CVD, PSA, age and five sphingolipids (HexCer.20, Cer.20, HexCer.24.1, GM3.24.1, DHCer.24) as key variables to accurately classify PCa (average ROC AUC on the 10 test sets: 0.92 vs 0.85 for PSA). In men recalled for SLI, PSA showed poor discriminatory ability, but PSA, age, CVD, SM.16, HexCer.20, HexCer.24.1, DHS1P, and DHCer.24 were consistently selected by 10/10 models (average ROC AUC: 0.83 vs 0.65 for PSA). Cer.20 and CVD or CVD alone were key variables also for the discrimination of ISUP>1 PCa within the entire cohort or within men recalled for SLI, respectively.
Conclusions
The evaluation of individual risk factors and circulating sphingolipids may allow for a more accurate identification of PCa in the context of tailored screening.
