Review of novel liquid-based biomarkers for prostate cancer: towards personalised and targeted medicine

Abstract

Background: Prostate cancer is the most commonly diagnosed cancer in men and it is responsible for about 10% of all cancer mortalities in both American and Canadian men. At present, serum prostate-specific antigen levels remain the most commonly used test to detect prostate cancer, and the standard and definitive diagnosis of the disease is via prostate biopsy. Conventional tissue biopsies are usually invasive, expensive, painful, time-consuming, and unsuitable for screening and need to be consistently evaluated by expert pathologists and have limited repeatability. Consequently, liquid biopsies are emerging as a favourable alternative to conventional tissue biopsies, providing a non-invasive and cost-effective approach for screening, diagnosis, treatment and monitoring of prostate cancer patients. Materials and methods: We searched several databases from August to December 2020 for relevant studies published in English between 2000 and 2020 and reporting on liquid-based biomarkers available in detectable quantities in patient bodily fluid samples. In this narrative review paper, we describe seven novel and promising liquid-based biomarkers that potentially account for individual patient variability as well as used in disease risk assessment, screening for early disease detection and diagnosis, identification of patients’ risk for metastatic disease and subsequent relapse, monitoring patient response to specific treatment and providing clinicians the potential to stratify patients likely to benefit from a particular treatment. Conclusions: The concept of precision medicine from prevention to treatment techniques that take individual patient variability into account will depend on the development of effective clinical biomarkers that interrogate key aberrant pathways potentially targetable with molecular targets or immunologic therapies. Liquid-based biomarkers with high sensitivity and specificity for prostate cancer are emerging as minimally invasive, lower risk, readily obtainable and easily repeatable technique for screening for early disease detection and diagnosis, patient stratification at diagnosis into different risk categories, identification of patients’ risk for metastatic disease and subsequent relapse, and real-time monitoring of patient response to specific treatment. Thus, effective liquid-based biomarkers will potentially shift the treatment paradigm of prostate cancer towards more personalised and targeted medicine.

Review of novel tissue-based biomarkers for prostate cancer: towards personalised and targeted medicine

“…88 Prostate-specific membrane antigen (PSMA) Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein with several enzymatic activities and it is encoded by the PSMA (or FOLH1, folate hydrolase 1) gene located on the short arm of chromosome 11 at position 11.12 (11p11.12). 11,[96][97][98][99][100][101][102][103] According to Bouchelouche et al, 97 PSMA is expressed in secretory cells within the prostatic epithelium and is absent or moderately expressed in hyperplastic and benign tissue. Xiao et al 103 reported that, since the discovery of PSMA, a variety of techniques such as tissue immunohistochemistry, reverse transcription PCR, in situ hybridisation and Western blot analysis have been used to demonstrate that it is expressed predominantly in prostate tissue, thus it is downregulated in BPH, but overexpressed in primary, metastatic prostate carcinoma and in patients with recurrences after androgen deprivation therapy.…”

“…At present, serum PSA level is the most commonly used test for the detection of prostate cancer, although these levels can also be elevated in benign conditions, have limited specificity and result in high rates of overdiagnosis and treatment of a significant number of indolent disease. 5,[7][8][9][10][11] According to Hessels et al, 12 PSA-based opportunistic screening has led to an increase in prostate cancer overdiagnosis and overtreatment due to the high incidence of clinically insignificant disease. Therefore, in order to shift the treatment paradigm of prostate cancer towards more patient-specific and targeted therapy, there is a need for a clear system that makes its detection binary so as to minimise the rate of inaccurate detections.…”

“…Therefore, in order to shift the treatment paradigm of prostate cancer towards more patient-specific and targeted therapy, there is a need for a clear system that makes its detection binary so as to minimise the rate of inaccurate detections. 5,11,13,14 Consequently, several studies have investigated the potential of new biomarkers capable of improving prostate cancer diagnosis, prognosis and treatment prediction to help avoid unnecessary biopsies and to discriminate aggressive from slow-growing cancers, thus avoiding overtreatment. 4,[6][7][8][9][10]12, Biomarkers commonly used for diagnosis, prognostication and therapeutic monitoring can be obtained through either liquid or tissue biopsies and the conventional tissue biopsies are typically surgical biopsy, radiologically guided biopsy or endoscopic biopsy.…”

“…According to Osei et al, 13,14 understanding the molecular mechanisms and signalling pathways of biomarkers can potentially lead to more personalised and targeted treatment via therapeutic targeting of specific genetically aberrant pathways which play key roles in cancer formation and may provide optimal treatment choices in clinical practice. In a previous study, Osei and Swanson 5 presented a comprehensive literature review of currently available clinical biomarkers and more recently, Osei et al 11 reported on novel and promising liquid-based biomarkers for the management of prostate cancer. In this narrative review paper, we describe 11 novel and promising tissue-based prostate cancer biomarkers used in risk assessment, screening for early detection and diagnosis, identification of patients' risk for metastatic disease and subsequent relapse, monitoring patient response to specific treatment and to provide clinicians the potential of prospectively identifying groups of patients who will benefit from a particular treatment.…”