Prostate cancer biomarkers: Are we hitting the mark?

Abstract

PurposeLocalised prostate cancer diagnosis and management is increasingly complex due to its heterogeneous progression and prognostic subgroups. Pitfalls in current screening and diagnosis have prompted the search for accurate and invasive molecular and genetic biomarkers for prostate cancer. Such tools may be able to distinguish clinically significant cancers from less aggressive variants to assist with prostate cancer risk stratification and guide decisions and healthcare algorithms. We aimed to provide a comprehensive review of the current prostate cancer biomarkers available and in development.MethodsMEDLINE and EMBASE databases searches were conducted to identify articles pertaining to the use of novel biomarkers for prostate cancer.ResultsA growing number of novel biomarkers are currently under investigation. Such markers include urinary biomarkers, serology-based markers or pathological tissue assessments of molecular and genetic markers. While limited clinical data is present for analysis, early results appear promising. Specifically, a combination of serum and urinary biomarkers (Serum PSA + Urinary PCA3 + Urinary TMPRSS2-ERG fusion) appears to provide superior sensitivity and specificity profiles compared to traditional diagnostic approaches (AUC 0.88).ConclusionThe accurate diagnosis and risk stratification of prostate cancer is critical to ensure appropriate intervention. The development of non-invasive biomarkers can add to the information provided by current screening practices and allows for individualised risk stratification of patients. The use of these biomarkers appears to increase the sensitivity and specificity of diagnosis of prostate cancer. Further studies are necessary to define the appropriate use and time points of each biomarker and their effect on the management algorithm of prostate cancer.

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence

“…The 22‐gene Decipher predicts metastasis following RP (Erho et al ., 2013; Karnes et al ., 2013; Klein et al ., 2016). While these and other biomarkers assist decision making and thus improve patient management, their clinical application requires further validation (Lamy et al ., 2017; Martin, 2016; McGrath et al ., 2016; Patel and Gnanapragasam, 2016; Ross et al ., 2016; Zhuang and Johnson, 2016). There is a clear need to improve our ability to stratify PCs with high risk of recurrence following RP.…”

What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective

“…The 4K score test (Opko Health Inc.) includes the panel of 4 kallikrein proteins (fPSA, tPSA, iPSA, and hK2) plasma levels and has also been developed to differentiate between patients with aggressive PCa eligible for biopsy and those with low risk and benign lesions [33,34]. Similarly to PHI, the potential of kallikreins combination to improve detection specificity and thus reduce costs has…”

“…Another technical problem of RNA instability has also been addressed recently, as RNA extraction efficiency can be potentially improved with novel RNA sequence-specific capture resulting in better sensitivity and specificity [43]. In a majority of studies performed with Progensa, PCA3 score of <25 implies low risk of PCa [34,[44][45][46]. The meta-analysis on multi-centre European prospective studies confirmed however that clinical aid brought by PCA3 does not end with detection of cancer but also includes stratification of its significance [47].…”

“…Genepanel was derived from signaling pathways relevant to stromal response (BGN, COL1A1 and SFRP4), proliferation (TPX2), androgen receptor pathway (AZGP1, KLK2, SRD5A2, and RAM13C) and cellular organization (FLNC, GSN, TPM2, and GSTM2) -all normalized to 5 reference genes [34,56]. Oncotype DX has been originally developed as a valuable predictive tool in detecting breast cancer, but to date it has also been analyzed in cohorts of men diagnosed with low or low-intermediate risk PCa who might be candidates for AS [57,58].…”

“…The test is performed on paraffin-embedded specimens. Analytical outcome is represented by the CCP score correlated with the proliferation index of PCa and serving as the postoperative risk stratification tool [34]. In the first 2 validation studies by Cuzick et al [59,60], CCP was the strongest prognostic factor in a multivariate analysis for predicting BCR and time to PCa-specific death.…”