Testosterone Levels Correlate With Grade Group 5 Prostate Cancer: Another Step Toward Personalized Medicine

BACKGROUND: Controversial results have shown a significant association with either low or high total testosterone (tT) levels and high risk prostate cancer (PCa). We tested the relationship between circulating tT and grade group 5 (G5) PCa at radical prostatectomy (RP) in patients with preoperative low- to intermediate-risk disease. METHODS: Serum sex hormones were assessed the day before RP in a cohort of 846 patients with low- to intermediate-risk PCa. Patients were segregated using the new 5-tiered Gleason grade groups. Restricted cubic spline functions and logistic regression analyses tested the association between sex hormones and G5 PCa. Differences in potential predictive accuracy (PA) were assessed for tT and prostate-specific antigen (PSA) levels. RESULTS: Overall, 27 men (3.2%) had G5 PCa at RP, and this group had higher PSA values than patients with G1–G4 PCa (P = 0.02). The groups did not differ in terms of preoperative mean hormonal values. Both low and high circulating tT values depicted a nonlinear U-shaped correlation with G5 PCa at RP. The lowest and highest (10th and 90th percentiles) tT values and biopsy PCa grade emerged as multivariable independent predictors of G5 PCa at RP (all P < 0.05). PA for G5 PCa did not differ between tT (area under the curve [AUC] 0.631) and PSA (AUC 0.636). CONCLUSIONS: Circulating tT was a significant predictor of G5 PCa at RP in patients with preoperative low- to intermediate-risk disease. Preoperative tT and PSA values showed similar PA for the most aggressive disease, confirming a potential role for circulating androgens in preoperative risk assessment of PCa patients. Prostate 77:234–241, 2017

Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis

Abstract Localized prostate cancer is frequently composed of multiple spatially distinct tumors with significant inter- and intra-tumoral molecular heterogeneity. This genomic diversity gives rise to many competing clones that may drive the biological trajectory of the disease. Previous large-scale sequencing efforts have focused on the evolutionary process in metastatic prostate cancer, revealing a potential clonal progression to castration resistance. However, the clonal origin of synchronous lymph node (LN) metastases in primary disease is still unknown. Here, we perform multi-region, targeted next generation sequencing and construct phylogenetic trees in men with prostate cancer with synchronous LN metastasis to better define the pathologic and molecular features of primary disease most likely to spread to the LNs. Collectively, we demonstrate that a combination of histopathologic and molecular factors, including tumor grade, presence of extra-prostatic extension, cellular morphology, and oncogenic genomic alterations are associated with synchronous LN metastasis