The number of altered pathways in aggressive prostate cancer is prognostic (60); we therefore created a score in cfDNA using 5hmC-seq inferred gain or loss of the eight most commonly altered prostate cancer driver genes by targeted cfDNA-seq (AR, MYC, NCOA2, RB1, TP53, BRCA2, PTEN, NKX3-1). Here, NKX3-1 is linked to prostate cancer.