Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes (n = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96–3.77, and p = 1.77 × 10−9 in The Cancer Genome Atlas (TCGA) PanCancer cohort (n = 492) and HR 2.72, 95% CI 1.84–4.01, and p = 4.99 × 10−7 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, p = 1.13 × 10−11), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.