Abstract
Prostate cancer is one of the most frequent cancers in men and is a common cause of cancer-related death. Despite significant progress in the diagnosis and treatment of this tumor, patients who relapse after radical treatments inevitably develop metastatic disease. Patient stratification is therefore key in this type of cancer, and there is an urgent need for prognostic biomarkers that can define patients’ risk of cancer-related death. In the last 10 years, multiple prognostic factors have been identified and studied. Here, we review the literature available and discuss the most common aberrant genomic pathways in metastatic castration-resistant prostate cancer shown to have a prognostic relevance in this setting.
Highlights
Prostate cancer (PC) is the second most common cancer for incidence and the fifth most frequent cause of cancer-related mortality in men worldwide, while in Western countries it represents the second cause of death for cancer in males [1,2]
A biomarker study of 163 docetaxel-treated patients assessed the association between plasma androgen receptor (AR) and outcomes in metastatic CRPC (mCRPC), reporting only a significant worse overall survival (OS) in AR-gained patients (HR = 1.61, 95%CI 1.08–2.39, p = 0.018)
The results demonstrated that Breast cancer-associated gene2 (BRCA2)-mutation carriers were characterized by a higher Gleason Score (GS) (>7), TNM stage (>T3, N1, M1) at diagnosis [66]
Summary
Prostate cancer (PC) is the second most common cancer for incidence and the fifth most frequent cause of cancer-related mortality in men worldwide, while in Western countries it represents the second cause of death for cancer in males [1,2]. These may include AR gene mutations, AR splicevariants, an AR gene amplification; the presence of AR co-regulators may contribute to resistance to treatments [16,17] These aberrations are seen to increase during tumor progression: in the setting of castration resistance, they are reported in 10–15% of patients, while they are identified in up to 40% of cases in patients treated with second or further treatment lines for advanced CRPC [18]. A biomarker study of 163 docetaxel-treated patients assessed the association between plasma AR and outcomes in mCRPC, reporting only a significant worse OS in AR-gained patients (HR = 1.61, 95%CI 1.08–2.39, p = 0.018). The findings from this study would suggest that AR-normal men could benefit from hormonal treatment in the first-line therapy group, while plasma AR-gained patients had a better response to docetaxel. This work provided innovative insights on utility of integrating functional imaging with plasma DNA analysis including AR status assessment and other noninvasive biomarkers to improve treatment
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