Germline or somatic BRCA1/2 mutation OR broader HRR pathway alteration (ATM, CDK12, PALB2...

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

ID	`RF-PROSTATE-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	pending_clinical_signoff
Diseases	`DIS-PROSTATE`
Sources	`SRC-ESMO-PROSTATE-2024` `SRC-NCCN-PROSTATE-2025`

Red Flag Origin

Definition	Germline or somatic BRCA1/2 mutation OR broader HRR pathway alteration (ATM, CDK12, PALB2, etc.) — predicts PARPi response; opens olaparib/talazoparib indication in mCRPC.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-PROSTATE-MCRPC-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-BRCA-GERMLINE",
      "value": "positive"
    },
    {
      "finding": "BIO-HRR-PANEL",
      "value": "positive"
    },
    {
      "finding": "brca1_mutation",
      "value": true
    },
    {
      "finding": "brca2_mutation",
      "value": true
    },
    {
      "finding": "hrr_pathway_mutation",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

PROfound (olaparib) + TALAPRO-2 (talazoparib + enzalutamide) + MAGNITUDE (niraparib + abiraterone) define PARPi indications. BRCA1/2 largest benefit; broader HRR cohort smaller but positive. Germline + somatic testing recommended for ALL metastatic patients per NCCN 2025.

Used By

Algorithms

ALGO-PROSTATE-MCRPC-1L - ALGO-PROSTATE-MCRPC-1L

Indications

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

Red flag

RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE - Germline pathogenic variant in ATM, CHEK2, or CDK12 (composite HRR-pathway RF). Disease-s...
RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE - Somatic (tumor-only) BRCA1 or BRCA2 pathogenic variant identified on tumor NGS — pan-tumo...
RF-PAN-PALB2-PARPI-CANDIDATE - Germline PALB2 pathogenic variant — BRCA2's recruitment partner; biallelic LOF produces a...