AR (androgen receptor) gene amplification detected on tumor or ctDNA NGS in mCRPC — INFOR...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-PROSTATE-AR-AMP-ARSI-RESISTANCE`
Type	Red flag
Status	reviewed 2026-04-29 \| pending_clinical_signoff
Diseases	`DIS-PROSTATE`
Sources	`SRC-EAU-PROSTATE-2024` `SRC-ESMO-PROSTATE-2024` `SRC-NCCN-PROSTATE-2025`

Red Flag Origin

Definition	AR (androgen receptor) gene amplification detected on tumor or ctDNA NGS in mCRPC — INFORMATIONAL signal of mechanistic ARSI resistance. AR amplification is one of the most common acquired resistance mechanisms to abiraterone / enzalutamide / apalutamide / darolutamide; detected in ~30-50% of post-ARSI mCRPC ctDNA samples. AR-amp argues against ARSI-after-ARSI sequencing (limited cross-class benefit) and for early switch to taxane chemotherapy (docetaxel, cabazitaxel) or radioligand 177Lu-PSMA-617 (if PSMA-PET-positive). FDA has NOT approved any therapy decision keyed on AR-amp status — surfaces in MDT brief to flag patients in whom further ARSI escalation is unlikely to add benefit. Companion to RF-PROSTATE-AR-V7-ARSI-RESISTANCE (AR-V7 splice variant); both detect distinct facets of AR-driven resistance.
Clinical direction	investigate
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "ar_amplification",
      "value": "positive"
    },
    {
      "finding": "ar_amp",
      "value": "positive"
    },
    {
      "finding": "ar_copy_number",
      "value": "amplified"
    },
    {
      "finding": "androgen_receptor_amplification",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

References BIO-AR-AMPLIFICATION. Detection: ctDNA NGS (Guardant360, FoundationOne Liquid CDx) is the practical platform — tumor biopsy in mCRPC frequently fails (bone-only disease, low cellularity). Co-occurring resistance markers include AR-V7 splice variant, AR LBD point mutations (L702H, T878A, F877L), and lineage plasticity (neuroendocrine transformation). Priority 76 chosen to fall just below RF-PROSTATE-AR-V7-ARSI-RESISTANCE (75) — both are informational and complementary; AR-V7 evidence (PROPHECY) prospectively validated, AR-amp evidence largely retrospective ctDNA cohorts. KB scope choice: ships as biomarker + RF (informational) only — no new IND, no algorithm step. Tx-modifying signal deferred to a future taxane-mCRPC IND chunk that branches on AR-amp / AR-V7 / LBD-mutation status.

Used By

Indications

IND-PROSTATE-MCRPC-1L-ARPI - IND-PROSTATE-MCRPC-1L-ARPI
IND-PROSTATE-MHSPC-1L-ARPI-DOUBLET - IND-PROSTATE-MHSPC-1L-ARPI-DOUBLET
IND-PROSTATE-MHSPC-1L-TRIPLET - IND-PROSTATE-MHSPC-1L-TRIPLET