New strategy for the identification of prostate cancer: The combination of Proclarix and the prostate health index

Abstract

Objectives: Prostate health index (PHI) and, more recently, Proclarix have been proposed as serum biomarkers for prostate cancer (PCa). In this study, we aimed to evaluate Proclarix and PHI for predicting clinically significant prostate cancer (csPCa).Patients and Methods: Proclarix and PHI were measured using samples of 344 men from two different centers. All patients underwent prostate biopsy, and among those, 188 men with PCa on biopsy had an additional radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/ml. Evaluation of area under the curve (AUC) and performance at predefined cut-offs of Proclarix and PHI risk scores as well as the linear combination thereof was performed to predict csPCa. PSA density was used as an independent comparator. Results:The cohort median age and PSA were 65 (interquartile range [IQR]: 60−71) and 5.6 (IQR: 4.3−7.2) ng/ml, respectively. CsPCa was diagnosed in 161 (47%) men based on the RP specimen. ROC analysis showed that Proclarix and PHI accurately predicted csPCa with no significant difference (AUC of 0.79 and 0.76, p = 0.378) but significantly better when compared to PSA density (AUC of 0.66, p < 0.001). When using specific cut-offs, Proclarix (cut-off 10) revealed higher specificity and positive predictive value than PHI (cut-off 27) at similar sensitivities. The combination of Proclarix and PHI provided a significant increase in the AUC (p ≤ 0.007) compared to the individual tests alone and the highest clinical benefit was achieved. Conclusion:Results of this study show that both Proclarix and PHI accurately detect the presence of csPCa. The model combining Proclarix and PHI revealed the synergistic effect and improved the diagnostic performance of the individual tests.

A Neural Network Model Combining [-2]proPSA, freePSA, Total PSA, Cathepsin D, and Thrombospondin-1 Showed Increased Accuracy in the Identification of Clinically Significant Prostate Cancer

“…Combining the single biomarkers of PHI and Proclarix by the ANN approach rather than the final scores by logistic regression analysis, as in our previous work [5], we achieved an improvement in specificity (68% vs. 49%, respectively) for csPCa identification.…”

“…We selected the blood-based proteins of PHI and Proclarix tests as several authors showed that they were significantly associated with an increased risk for a positive biopsy and for a GS of ≥7 at RP [5,[20][21][22].…”

“…The Proclarix score is obtained using thrombospondin-1 (THBS1), cathepsin D (CTSD), total PSA (tPSA), free PSA (fPSA), and patient age values [4]. We previously demonstrated that the combination of PHI and Proclarix test results synergistically improved the diagnostic performance of the individual test [5]. On this basis, we hypothesized that it could be valuable to explore whether a new model comprising the kallikrein markers included in PHI and the cancer-related markers of Proclarix may achieve higher values of sensitivity and specificity for the detection of both all cancers and csPCa than the tests alone.…”

“…The levels of (i) total PSA (tPSA), (ii) free PSA (fPSA), (iii) the isoform-2 of proPSA (p2PSA), (iv) thrombospondin-1 (THBS1), and (v) cathepsin D (CTSD) were determined in 344 patients using automated immunometric and ELISA assays. Based on our previous studies [1][2][3][4][5][8][9][10], a model containing those variables can potentially detect PCa and csPCa early with higher accuracy compared with PHI and Proclarix individual test results. As shown in a recently published systematic review [11], several studies demonstrated the potential of ANNs for the identification and validation of PCa biomarkers.…”

Evaluation of Proclarix in the diagnostic work‐up of prostate cancer

“…13 This test, which incorporates serum total PSA (tPSA), free PSA (fPSA), cathepsin D (CTSD), thrombospondin 1 (THBS1) and patient age, 14 has been shown to detect csPCa with more favourable diagnostic performance characteristics as compared to percent fPSA (%fPSA) and the ERSPC risk calculator. [15][16][17][18][19][20][21][22] One limitation of the available literature on the Proclarix test is that all papers relied upon the results of a 10-14 core systematic biopsy of the prostate with or without targeted biopsy core. 15,[18][19][20] Although this practice is typical in the prostate cancer biomarker literature, concerns remain regarding the accuracy of this somewhat limited method of sampling the prostate.…”