Table 1.

Predictive/prognostic biomarkers and screening tests in management of advanced PCa

Class	Marker	Description	Clinical utility	Ref
Mainstream diagnostic markers Clinically and commercially available	PSA	First-Line treatment	Screening and monitoring PCa	[4]
	Total PSA, free-PSA, p2PSA isoform/serum	Prostate Health Index (PHI)	Prediction of high grade PCa Avoiding unnecessary biopsies Improve the performance of serum PSA	[5, 6]
	Total PSA, free-PSA, intact PSA, hK2 /serum	4-kallikrein score (4Kscore)	Risk prediction for mPCa Avoiding unnecessary biopsies	[5, 6]
	HOXC6 and DLX1 mRNA/post-DRE urine	SelectMDx	Predictive for high grade PCa	[5, 6]
	Exosomal level of RNA expression of three genes (e.g., SPDEF, ERG and PCA3)/urine	ExoDx Prostate Intelliscore (EPI)	predictive for the probability of high-grade PCa from Grade Group (GG) 2 or higher	[5, 6]
	PCA3 and TMPRSS2-ERG mRNA, PSA/post-DRE urine	MyProstateScore (MPS)	Avoiding unnecessary biopsies	[5, 6]
	22-gene microarray-based genomic classifier (GC)	Decipher (post-PR testing)	Risk estimating for metastases development	[7]
Genotypic biomarkers	Genome-wide association studies (GWAS)	High-throughput genotyping	Uncovering the genomic variants associated-risk in developing a trait/disease	[8]
	Polygenic risk scores (PRSs)	Numerical indicators	Estimating the individual's genetic liability to a trait/disease	[9]
	AR point mutations, AR amplifications, and AR variants HSD3B1(1245C) genotype	Androgen receptor (AR)	Potentially predictive for optimal treatment Worse OS and early development of CRPC Potentially predictive for time of progression to CRPC in response to ADT	[10–13] [14–17]
	PTEN loss	PTEN and PI3K-AKT pathway	Lack of response to abiraterone acetate, but a more desirable response to docetaxel Potentially predictive for AKT inhibitors Poor survival	[18, 19]
	Homologous recombination deficiency (HRD); BRCA2, ATM, CDK12, and BRCA1 variants Mismatch repair deficiency (MMRd); MSH2 and MSH6 mutations	DNA damage response (DDR)	Predictive for PARP inhibitors Worse prognosis Potentially predictive for PD-1 inhibitors Shorter OS	[20–22] [23–25]
	CTCs and ctDNA RNA-based fragments Exosomes	Reducing the necessity of invasive biopsies	Commercially available/clinical usage Clinical trial Clinical trial	[26, 27]
Phenotypic biomarkers (Clinical trials)	Serum testosterone level (pre-treatment)	Levels ≥ 5 ng/dL vs. < 5 Levels > 0.05 vs. 0.05 > ng/mL	levels ≥ 5 ng/dL; patients benefit more from AR-targeted therapy/longer PSA-PFS and OS Levels < 5; treatment with abiraterone; prolonged PSA-PFS and higher PSA response Levels > 0.05 ng/mL; treatment with enzalutamide; superior PFS, while worse PFS with docetaxel	[28] [29]
	SLFN11 expression	Overexpression of SLFN11	Predictive for platinum-based chemotherapy/longer radiographic PFS, diminishing PSA ≥ 50%	[30]
	Total alkaline phosphatase (tALP)	Normalization of tALP	prognostic for OS Treatment with Radium-223; better OS	[31]
	Neutrophil-to-lymphocyte ratio (NLR)	Higher baseline NLR NLR ≤ 5 vs. NLR > 5 NLR ≥ 2.5 vs. NLR < 2.5	Receiving abiraterone; worse OS Receiving enzalutamide; inferior OS and CSS Treatment with 223Ra; improved OS Better 1-year rPFS and 2-year CSS; received post-docetaxel ARAT agents compared to patients with pre-docetaxel ARAT Lower 1-year rPFS and 2-year CSS	[32] [33] [33]
	PD-L1 expression	Tumor pathology	Higher risk of progression Higher risk of recurrence after radical prostatectomy Immune checkpoint-inhibiting therapies	[34]
	PSMA and choline proteins	Radioligand-based imaging modalities	Detecting nodal and distant metastatic disease	[35]