Clinical History & Chronological Summary:
• Diagnosis: 70-year-old male with metastatic prostate
adenocarcinoma (T3bN3M1), Gleason 9 (5+4), with
seminal vesicle invasion, bladder wall infiltration,
and necrotic pelvic lymph nodes.
• Imaging: PET-CT revealed prostatomegaly with
locally invasive lesion.
• Histopathology: TURP chips and urethral polyp
biopsy confirmed poorly differentiated
adenocarcinoma, IHC positive for PSA, AMACR,
NKX3.1.
• Treatment: Initiated Degarelix and Denosumab
(X-Geva).
• Further evaluation: Comprehensive molecular
profiling (OncoIndx Prime) performed on FFPE tissue
and plasma cfDNA/RNA to guide targeted treatment
options.
Clinical Challenges:
• Aggressive disease biology with high Gleason grade
and local invasion.
• Therapeutic resistance was expected due to strong AR
signaling from TMPRSS2-ERG fusion and FOXA1
overexpression.
• Dual molecular phenotype (MSI-High, PD-L1 positive)
creating uncertainty in therapy sequencing.
• Variants of uncertain significance (CHD4, SMARCA4,
DICER1) complicated interpretationx