Clinico-Pathological Factors and AR-LBD Mutations in Early and Late Castration-Resistant Prostate Cancer.

Area of Science:

• Oncology
• Urology
• Cancer Biology

Background:

• Prostate cancer (PCa) exhibits significant biological heterogeneity, complicating its progression and management.
• Understanding the factors predicting early versus late progression to castration-resistant prostate cancer (CRPC) is crucial for improved patient care.

Purpose of the Study:

• To identify clinical and pathological variables associated with early and late progression to CRPC.
• To explore the correlation between androgen receptor (AR) gene sequences and CRPC development.

Main Methods:

• Retrospective analysis of 98 CRPC patients diagnosed between January 2018 and January 2022.
• Stratification of patients into quartiles based on time to castration resistance (TTCR).
• Comparison of early CRPC (6-12 months TTCR) and late CRPC (38-120 months TTCR) groups based on clinical, pathological, and AR-LBD sequence data.

Main Results:

• Median time to castration resistance was 25 ± 26.44 months.
• Higher Gleason score (≥7) was significantly associated with early CRPC development (p<0.001).
• Lower nadir PSA levels were significantly correlated with late CRPC progression (p<0.005).
• A homozygous mutation in the 7th intronic region of the AR gene was identified, potentially influencing splice variants in CRPC.

Conclusions:

• Prostate cancer progression to CRPC is heterogeneous, with a wide range in time to resistance.
• Early age, high initial PSA, and high Gleason score are associated with early CRPC.
• Lower nadir PSA is a predictor of late CRPC progression.
• No significant genomic mutations were found, highlighting the need for further research into predictive biomarkers.