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OpenOnco · DIS-ENDOMETRIAL · BIO-TP53-IHC (ESCAT IB)
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OpenOnco · Treatment Plan
Treatment plan — Endometrial carcinoma
PLAN-BMA-TP53_IHC_ENDOMETRIAL-V1 · v1 · 2026-08-03
Patient
BMA-TP53_IHC_ENDOMETRIAL · Algorithm: ALGO-ENDOMETRIAL-ADVANCED-1L
DiagnosisEndometrial carcinoma
MOH / ICD-10C54
ICD-O-38380/3; C54.1

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
ESCAT: clinical review pendingBIO-TP53-IHCp53-aberrant IHC pattern: either (a) diffuse strong nuclear staining >80% of tumor cell nuclei (overexpression, missense surrogate) OR (b) complete absence of nuclear staining with intact internal controls — endothelium/stroma must stain positive (null pattern, nonsense/frameshift surrogate). Equivocal (heterogeneous, patchy <80% or wild-type-pattern) = p53-wildtype by IHC. Note: BIO-TP53-IHC (this entry) ≠ BIO-TP53-MUTATION — IHC is the clinical surrogate used in ESMO 2023 molecular subtyping; sequencing confirmation optional but not required for guideline application. IB
Standard care
  • SRC-ESMO-ESGO-ESTRO-ENDOMETRIAL-2023: Level A (Supports, Sensitivity/Response)
  • SRC-NCCN-UTERINE-2025: Level Category 1 (Supports, Sensitivity/Response)
p53-aberrant (p53-abn) endometrial carcinoma defines the highest-risk molecular subgroup per the ProMisE/TCGA/ESMO 2023 molecular classification (corresponding to "copy-number-high/serous-like" TCGA group). p53-abn tumors are typically high-grade, often serous or clear-cell histology, with the worst prognosis (5-yr OS ~55-60% in early-stage vs ~90% for POLE-ultramutated). PORTEC-3 (de Boer et al. Lancet 2019 / Oncology 2022 update): phase III RCT, 686 pts high-risk endometrial carcinoma; adjuvant chemoradiotherapy (cisplatin 45 Gy EBRT + carboplatin/paclitaxel x4 cycles) vs pelvic RT alone. Primary results: 5-yr failure-free survival 75.5% vs 68.6% (HR 0.71, p=0.022); 5-yr OS 81.4% vs 76.1% (HR 0.70, p=0.034). Molecular subgroup analysis (León-Castillo et al. JCO 2020): among p53-abn tumors (n=150), chemoRT benefit was largest — HR for FFS 0.52 (95% CI 0.30–0.89); whereas no benefit was observed in MMRd or NSMP subgroups. This biomarker-treatment interaction analysis is the primary evidence for ESMO 2023 escalation recommendation. ESMO-ESGO-ESTRO 2023 guidelines: p53-abn molecular subtype → recommended for adjuvant chemoRT ± maintenance chemotherapy regardless of stage. NCCN Uterine Neoplasms 2025: p53-abn molecular subtype is Category 1 indication for adjuvant combination chemotherapy + external beam RT (chemoRT) in high-risk patients. Standard carboplatin AUC5 + paclitaxel 175 mg/m² q3w x4-6 cycles combined with or sequenced around EBRT. Additional support: PORTEC-4a trial (ongoing) evaluates adjuvant therapy de-escalation/escalation based on molecular subtype — early data further validate molecular triage including p53-abn as high-risk group requiring escalation. The actionability here is PREDICTIVE (not merely prognostic): p53-abn specifically predicts benefit from chemotherapy intensification BEYOND standard RT, guiding treatment selection in clinical practice.Carboplatin AUC5 + paclitaxel 175 mg/m² q3w x4-6 cycles ± concurrent EBRT (45 Gy) — PORTEC-3 chemoRT regimen
Sequential approach: EBRT 45 Gy → carboplatin/paclitaxel x4 (or vice versa per institutional preference)
Vaginal brachytherapy (VBT) may be added for vaginal cuff coverage
  • SRC-ESMO-ESGO-ESTRO-ENDOMETRIAL-2023
  • SRC-NCCN-UTERINE-2025
ESCAT: clinical review pendingBIO-TP53-MUTATIONany pathogenicIIIB
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)
TP53 mutation in ENDOMETRIAL — common, adverse prognostic; not directly targeted. Per usual algorithm.—
  • SRC-NCCN-UTERINE-2025

Primary current-line option

Standard plan
★ DEFAULT
Indication
IND-ENDOMETRIAL-ADVANCED-1L-PEMBRO-CHEMO
Regimen
Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L)
Drugs + NSZU
  • Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w · Continuous up to 2 years · IV ⚠ NSZU — not for this indication
  • Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
  • Paclitaxel (DRUG-PACLITAXEL) 175 mg/m² IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
Reason
Primary current-line option selected by ALGO-ENDOMETRIAL-ADVANCED-1L at step 1.

Other current-line alternatives (1 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
Aggressive plan
Indication
IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO
Regimen
Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR)
Drugs + NSZU
  • Dostarlimab (DRUG-DOSTARLIMAB) 500 mg IV q3w → 1000 mg q6w maintenance · With chemo cycles 1-6 + maintenance up to 3 years · IV ✗ Not registered in UA
  • Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
  • Paclitaxel (DRUG-PACLITAXEL) 175 mg/m² IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
Reason
Current-line alternative presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-CECT-CAPCECT chest/abdomen/pelvisCriticalimaging—all tracks
TEST-ER-PR-IHCER + PR immunohistochemistry on tumorCritical—CSD Lab ✓ (code TBC)all tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track
  • Patient with active or incompletely controlled pre-existing autoimmune or inflammatory disease (sarcoidosis, rheumatoid arthritis, IBD, SLE, autoimmune hepatitis, inflammatory myopathy, myasthenia gravis, or similar) is considered for immune checkpoint inhibitor (ICI) therapy — elevated risk of immune-related adverse events (irAE) flare or de-novo grade 3-4 irAE. Requires specialist (rheumatology / pulmonology / gastroenterology) pre-treatment review; prefer lower-irAE-burden backbone when options exist (pembrolizumab mono > ipilimumab+nivolumab).
    Pre-existing autoimmune disease is present in ~10-15% of patients eligible for ICI therapy; historically excluded from pivotal trials. Real-world data (Abdel-Wahab 2018, 3557 pts) shows 55% experienced irAE flare and ~29% required…
    RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISKSRC-SITC-ICI-IRAEMANAGEMENT-2021SRC-ESMO-ICI-TOXICITY-2022

CONTRA-AGGRESSIVE

Hard contraindications to escalation
  • —

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L)
21-day cycles × Chemo x 6; pembro maintenance up to 2 years

Aggressive plan

Induction · Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR)
21-day cycles × Chemo x 6; dostarlimab maintenance up to 3 years

MDT brief

Discussion questions (2, 0 blocking)

  • OQ-LDH-CURRENT
    What is the current LDH? Marker of tumor burden and transformation.
    LDH is part of the prognostic indices of indolent lymphomas.
    → hematologist
  • OQ-BIOMARKER-DMMR-IHC
    What is the status of Mismatch repair protein expression by IHC (BIO-DMMR-IHC)? It is required by track(s): IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO. Expected value: deficient.
    A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
    → pathologist

MDT talk tree (3 steps)

#OwnerTopicAction
1hematologistStaging / disease burden What is the current LDH? Marker of tumor burden and transformation.
2pathologistBiomarker status What is the status of Mismatch repair protein expression by IHC (BIO-DMMR-IHC)? It is required by track(s): IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO. Expected value: deficient.
3clinical_pharmacistSpecialist review Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (recommended) — for consideration (1)

  • Clinical pharmacist recommended
    Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

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: 0/1 known (0%), 1 missing, 0 default-track gaps
  • Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-CASCADE-LYNCH-FDR-POSITIVE, RF-CHRONIC-SEVERE-OBESITY-BMI40-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, RF-ENDOMETRIAL-FIT-FOR-LENVATINIB-COMBO, RF-ENDOMETRIAL-FRAILTY-AGE, RF-ENDOMETRIAL-HIGH-RISK-BIOLOGY, RF-ENDOMETRIAL-INFECTION-SCREENING, RF-ENDOMETRIAL-ORGAN-DYSFUNCTION, RF-ENDOMETRIAL-TRANSFORMATION-PROGRESSION, RF-IATROGENIC-COMBINED-HRT-PREVENTION, RF-IATROGENIC-TAMOXIFEN-ENDOMETRIAL-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-SEDENTARY-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK, RF-REPRODUCTIVE-BREAST-ENDOMETRIAL-PREVENTION, RF-REPRODUCTIVE-OCP-LONG-TERM, RF-REPRODUCTIVE-PCOS-ENDOMETRIAL-PREVENTION
Missing biomarkerLabelMDT ownerDefault trackRequired byNext action
BIO-DMMR-IHCMismatch repair protein expression by IHCpathologistnoIND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMOVerify result, method, specimen, and report date before sign-off. Expected/constraint: deficient
Technical MDT skill metadata (1/16 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)

Last synced: 2026-08-03 · ctgov.

No active trials matched this scenario in ctgov.

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
Standard plan
Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L) (REG-PEMBRO-CARBO-PACLI-ENDOM)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Aggressive plan
Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR) (REG-DOSTARLIMAB-CARBO-PACLI-ENDOM)
1/3 component drug(s) not registered in Ukraine +1
✗ not registered✗ out-of-pocket₴-? — verify pathwaynot recorded

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-03.

plan_id: PLAN-BMA-TP53_IHC_ENDOMETRIAL-V1 | version: 1 | generated: 2026-08-03T12:01:53.070731+00:00
Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.
Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.
This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.