Early-Onset Prostate Cancer: Epidemiology, Risk Factors, Biology, Clinical Features, Management, and Early Detection

Area of Science:

• Oncology
• Genetics
• Epidemiology

Background:

• Early-onset prostate cancer (EOPC) incidence is increasing, with projected rises in cases and mortality by 2045.
• EOPC is recognized as a distinct entity with unique molecular, risk, and clinical characteristics compared to standard-onset prostate cancer (SOPC).
• Current research on EOPC is limited, lacking consensus on optimal management strategies.

Purpose of the Study:

• To synthesize current evidence on EOPC's epidemiology, molecular pathology, clinicopathological features, survival, management, and early detection.
• To identify knowledge gaps, particularly concerning sporadic EOPC and the need for dedicated clinical trials.
• To propose future research directions for early detection and optimized therapeutic strategies for EOPC.

Main Methods:

• Systematic review and synthesis of existing literature on early-onset prostate cancer.
• Critical appraisal of epidemiological data, molecular pathology findings, and clinical characteristics.
• Analysis of survival data and current management approaches for EOPC.

Main Results:

• EOPC shows a distinct molecular profile, with TMPRSS2-ERG fusions prevalent (63-90%) and lower frequencies of PTEN, SPOP, and CHD1 mutations.
• Sporadic EOPC cases, which are more common, are understudied compared to hereditary forms.
• Localized EOPC has no significant survival advantage over SOPC, but high-risk or metastatic EOPC significantly increases mortality.

Conclusions:

• EOPC represents a unique clinical and molecular challenge requiring further investigation.
• Addressing the understudied sporadic EOPC subgroup and initiating dedicated clinical trials are crucial next steps.
• Optimizing early detection and therapeutic strategies for EOPC necessitates targeted research efforts.