Introduction: Pentraxin-3 (PTX3) belongs to the pentraxin superfamily, which are essential components of the humoral arm of the innate immune system and play a pivotal role in vascular biology. Like short pentraxins, PTX3 facilitates dysregulation of mitogenic signaling pathways, sustains cellular proliferation, angiogenesis, insensitivity to apoptosis, cancer cell invasion and migration, and tumor escape from immunosurveillance. Unlike short pentraxins, PTX3 is produced by a variety of cell types at the site of inflammation. Considering that chronic inflammation is found in as much as 80% of prostate biopsy (PBx) and that PTX3 seems to be involved in inflammatory-related carcinogenesis, we elected to test the potential correlation between PTX3 and PCa. Aim of the study is to test and internally validate serum Pentraxin-3 (PTX3) levels as a potential PCa biomarker to predict prostate biopsy (PBx) results.
Methods: Serum PSA and serum PTX3 were prospectively assessed in patients scheduled for PBx at our Institution because of increased serum PSA levels and/or abnormal Digital rectal examination. Uni- and multivariable logistic regression analysis, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA), were used to test the accuracy of serum PTX3 in predicting anyPCa and clinically significant PCa (csPCa) defined as Gleason Grade (GG) =2.
Results: Between the 455 eligible patients, PCa was detected in 49% and csPCa in 25%. At univariable analysis, PTX3 outperformed other variables in predicting both anyPCa and csPCa. The addition of PTX3 to multivariable models based onto standard clinical variables significantly increased each model predictive accuracy for anyPCa (AUC from 0.73 to 0.82; p<0.001) and csPCa (AUC from 0.79 to 0.83; p<0.001). At DCA, PTX3 and PTX3 density showed higher net benefit than PSA and PSA density and increased the net benefit of multivariable models in deciding when to perform PBx.
Conclusions: The present prospective study reports that serum PTX3 significantly outperforming serum PSA in predicting prostate biopsy results. Moreover, the addition of serum PTX3 to statistical models incorporating PSA and standard clinical variables significantly improved the model diagnostic accuracy, thus being of potential value in reducing the number and harms of unnecessary PBxs. Since non-malignant conditions may increases PSA levels, there is a great quest for an efficient second test, the so-called reflex test, that may reduce the number of unnecessary PBxs. Results of such additional test may be used alone or included in multivariable models that take into account multiple clinical and laboratory variables. Should our findings be confirmed, this novel reflex test could be used to reduce the number and burden of unnecessary prostate biopsies.