OpenOnco · Prostate · mCRPC · BRCA-mut · Olaparib (PROfound)
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OpenOnco · Treatment Plan
Treatment plan — Prostate adenocarcinoma
PLAN-PROSTATE-MCRPC-BRCA-001-V1 · v1 · 2026-05-13
Patient
PROSTATE-MCRPC-BRCA-001 · Algorithm: ALGO-PROSTATE-MCRPC-1L
DiagnosisProstate adenocarcinoma
MOH / ICD-10C61
ICD-O-38140/3; C61.9
StageIV

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
✅ Covered biomarkers (matched in KB)
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
BIO-HRR-PANELATM germline pathogenicIB
Molecular evidence option
Resistance or avoidance signal
Trial or research option
  • SRC-CIVIC: Level C (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level D (Supports, Sensitivity/Response)
ATM germline pathogenic in mCRPC: olaparib approved per PROfound (Cohort A included ATM); benefit smaller than BRCA but FDA/EMA-labeled. Talazoparib+enzalutamide and olaparib+abiraterone also include ATM in HRR- mutated populations. ESCAT IB / OncoKB Level 1.olaparib monotherapy (post-NHA)
talazoparib + enzalutamide (1L, HRR-mut)
  • SRC-NCCN-PROSTATE-2025
  • SRC-ESMO-PROSTATE-2024
  • SRC-EAU-PROSTATE-2024
BIO-HRR-PANELATM somatic loss-of-functionIB
Molecular evidence option
Resistance or avoidance signal
Trial or research option
  • SRC-CIVIC: Level C (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level D (Supports, Sensitivity/Response)
Somatic ATM loss-of-function in mCRPC: PROfound enrolled both germline and somatic ATM in Cohort A; olaparib indication covers both. ESCAT IB / OncoKB Level 1.olaparib monotherapy (post-NHA, FDA)
talazoparib + enzalutamide (1L, HRR-mut)
  • SRC-NCCN-PROSTATE-2025
  • SRC-ESMO-PROSTATE-2024
  • SRC-EAU-PROSTATE-2024
BIO-BRCA1-BRCA2-GERMLINEBRCA1 germline pathogenicIA
Molecular evidence option
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal
BRCA1 germline pathogenic in mCRPC: olaparib improves rPFS and OS post-NHA (PROfound Cohort A, de Bono 2020); rucaparib (TRITON2/3) and niraparib (MAGNITUDE BRCA subset) also approved. 1L olaparib + abiraterone (PROpel) and niraparib + abiraterone (MAGNITUDE) extend rPFS in HRR-positive mCRPC. ESCAT IA / OncoKB Level 1.olaparib monotherapy (post-NHA)
olaparib + abiraterone + prednisone (1L)
niraparib + abiraterone + prednisone (1L)
talazoparib + enzalutamide (1L)
rucaparib monotherapy (post-NHA + taxane)
  • SRC-NCCN-PROSTATE-2025
  • SRC-ESMO-PROSTATE-2024
  • SRC-EAU-PROSTATE-2024
BIO-HRR-PANELBRCA1 somatic loss-of-functionIA
Molecular evidence option
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal
Somatic BRCA1 loss-of-function in mCRPC: PROfound enrolled both germline and somatic; olaparib benefit equivalent. PARPi labels in prostate cover both gBRCA and sBRCA. ESCAT IA / OncoKB Level 1.olaparib monotherapy (post-NHA)
olaparib + abiraterone (1L)
niraparib + abiraterone (1L)
talazoparib + enzalutamide (1L)
  • SRC-NCCN-PROSTATE-2025
  • SRC-ESMO-PROSTATE-2024
  • SRC-EAU-PROSTATE-2024
BIO-BRCA1-BRCA2-GERMLINEBRCA2 germline pathogenicIA
Molecular evidence option
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal
Trial or research option
  • SRC-CIVIC: Level C (Supports, Sensitivity/Response)
BRCA2 germline pathogenic in mCRPC: largest PARPi benefit in HRR pathway (PROfound Cohort A); olaparib post-NHA, 1L olaparib+abiraterone (PROpel), niraparib+abiraterone (MAGNITUDE), talazoparib+enzalutamide (TALAPRO-2) all approved. ESCAT IA / OncoKB Level 1.olaparib monotherapy (post-NHA)
olaparib + abiraterone (1L)
niraparib + abiraterone (1L)
talazoparib + enzalutamide (1L)
rucaparib monotherapy
  • SRC-NCCN-PROSTATE-2025
  • SRC-ESMO-PROSTATE-2024
  • SRC-EAU-PROSTATE-2024
BIO-HRR-PANELBRCA2 somatic loss-of-functionIA
Molecular evidence option
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal
Trial or research option
  • SRC-CIVIC: Level C (Supports, Sensitivity/Response)
Somatic BRCA2 loss-of-function in mCRPC: PROfound included sBRCA; olaparib benefit equivalent to germline. Labels cover germline OR somatic. ESCAT IA / OncoKB Level 1.olaparib monotherapy
olaparib + abiraterone (1L)
niraparib + abiraterone (1L)
talazoparib + enzalutamide (1L)
  • SRC-NCCN-PROSTATE-2025
  • SRC-ESMO-PROSTATE-2024
  • SRC-EAU-PROSTATE-2024
BIO-HRR-PANELCHEK1 somatic loss-of-functionIIIA
Molecular evidence option
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
Somatic CHEK1 loss-of-function in mCRPC: rare; PROfound included CHEK1 in Cohort B but small sample. Olaparib FDA label includes CHEK1 in HRR list. ESCAT IIIA / OncoKB Level 3B.olaparib monotherapy (post-NHA, FDA HRR label)
  • SRC-NCCN-PROSTATE-2025
  • SRC-EAU-PROSTATE-2024
BIO-HRR-PANELCHEK2 germline pathogenicIB
Molecular evidence option
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level B (Supports, Predisposition)
Resistance or avoidance signal
CHEK2 germline pathogenic in mCRPC: included in PROfound Cohort B; olaparib FDA HRR label (post-NHA) includes CHEK2 (FDA), though EMA label restricts to BRCA1/2. ESCAT IB (FDA jurisdiction) / OncoKB Level 1.olaparib monotherapy (post-NHA, FDA HRR label)
talazoparib + enzalutamide (HRR-mutated 1L)
  • SRC-NCCN-PROSTATE-2025
  • SRC-ESMO-PROSTATE-2024
  • SRC-EAU-PROSTATE-2024
BIO-HRR-PANELCHEK2 somatic loss-of-functionIB
Molecular evidence option
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level B (Supports, Predisposition)
Resistance or avoidance signal
Somatic CHEK2 in mCRPC: PROfound enrolled both g/s; FDA olaparib HRR label includes CHEK2. ESCAT IB / OncoKB Level 1.olaparib monotherapy (FDA HRR label)
talazoparib + enzalutamide (HRR-mutated 1L)
  • SRC-NCCN-PROSTATE-2025
  • SRC-ESMO-PROSTATE-2024
  • SRC-EAU-PROSTATE-2024
⚠️ Not included in plan
BiomarkerStatus
BIO-GLEASON-ISUPBIO definition in KB; no ESCAT BMA entry — verify with clinician
BIO-PSABIO definition in KB; no ESCAT BMA entry — verify with clinician
BIO-BRCA-GERMLINEBIO definition in KB; no ESCAT BMA entry — verify with clinician

Primary current-line option

Aggressive plan
★ DEFAULT
Indication
IND-PROSTATE-MCRPC-1L-PARPI
Regimen
Olaparib monotherapy (mCRPC, HRR-mutant)
Drugs + NSZU
  • Olaparib (DRUG-OLAPARIB) 300 mg PO BID continuous · Until progression or unacceptable toxicity · PO ⚠ NSZU — not for this indication
Supportive care
SUP-BONE-HEALTH-PROSTATE
Reason
Primary current-line option selected by ALGO-PROSTATE-MCRPC-1L at step 1; branch-driving red flag: RF-PROSTATE-HIGH-RISK-BIOLOGY.

Why this branch was chosen

Triggers from the patient profile that fired and drove the chosen branch.
Step 1 → branch IND-PROSTATE-MCRPC-1L-PARPI
  • RF-PROSTATE-HIGH-RISK-BIOLOGY ★ winner: Germline or somatic BRCA1/2 mutation OR broader HRR pathway alteration (ATM, CDK12, PALB2, etc.) — predicts PARPi response; opens olaparib/talazoparib indication in mCRPC. SRC-NCCN-PROSTATE-2025SRC-ESMO-PROSTATE-2024

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-PSA-SERUMSerum PSACriticalall tracks
TEST-BONE-SCANWhole-body Tc-99m MDP bone scintigraphyStandardall tracks
TEST-GERMLINE-BRCA-PANELGermline BRCA1/2 + HRR panel sequencingStandardCSD Lab: M089all tracks
TEST-PSMA-PETPSMA-PET/CT (Ga-68 or F-18)Standarddesired (aggressive)
TEST-SOMATIC-HRR-PANELTumor-tissue (or ctDNA) HRR-pathway NGS panelStandardCSD Lab: M065
CSD Lab ✓ (code TBC)
all tracks
TEST-TESTOSTERONE-SERUMSerum total testosteroneStandardall tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track
  • Germline or somatic BRCA1/2 mutation OR broader HRR pathway alteration (ATM, CDK12, PALB2, etc.) — predicts PARPi response; opens olaparib/talazoparib indication in mCRPC.RF-PROSTATE-HIGH-RISK-BIOLOGY

CONTRA-AGGRESSIVE

Hard contraindications to escalation

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · Olaparib monotherapy (mCRPC, HRR-mutant)
28-day cycles × Continuous until progression

MDT brief

Discussion questions (1, 0 blocking)

MDT talk tree (3 steps)

#OwnerTopicAction
1hematologistStaging / disease burden What is the current LDH? Marker of tumor burden and transformation.
2clinical_pharmacistSpecialist review Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
3molecular_geneticistSpecialist review Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.

Skills (recommended) — for consideration (2)

  • Clinical pharmacist recommended
    Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
  • Molecular geneticist / molecular oncologist recommended
    Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.

Data quality

Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
  • Biomarker coverage: 3/3 known (100%), 0 missing, 0 default-track gaps
  • Unevaluated RedFlags: RF-CHAARTED-HIGH-VOLUME-MHSPC, RF-LATITUDE-HIGH-RISK-MHSPC, RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE, RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE, RF-PAN-PALB2-PARPI-CANDIDATE, RF-PROSTATE-AR-AMP-ARSI-RESISTANCE, RF-PROSTATE-AR-V7-ARSI-RESISTANCE, RF-PROSTATE-CORD-COMPRESSION, RF-PROSTATE-HIGH-RISK-BIOLOGY, RF-PROSTATE-INFECTION-SCREENING, RF-PROSTATE-ORGAN-DYSFUNCTION, RF-PROSTATE-PSA-PROGRESSION, RF-PROSTATE-TMPRSS2-ERG-PROGNOSTIC, RF-PROSTATE-TRANSFORMATION-PROGRESSION
Technical MDT skill metadata (2/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-13.
NCTTitlePhaseStatusSponsorUASignalsEligibility (excerpt)
NCT05498272Study of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With Select HRR Gene AlterationsPHASE2RECRUITINGRana McKay, MDSmall N (<50) Single country

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
OptionUA registrationNSZUCost orientationAccess pathway
Aggressive plan
Olaparib monotherapy (mCRPC, HRR-mutant) (REG-OLAPARIB-MONO)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Trial · NCT05498272
Study of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With Select HRR Gene Alterations
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-13.