Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
VERIFIED-UROTHELIAL-L2-UROTHELIAL_2L_EV · Algorithm: ALGO-UROTHELIAL-METASTATIC-2L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| No clinically actionable variants matched in this profile. |
Primary current-line option
- Indication
- IND-UROTHELIAL-2L-EV
- Regimen
- Enfortumab vedotin monotherapy (urothelial carcinoma)
- Drugs + NSZU
- Enfortumab vedotin (DRUG-ENFORTUMAB-VEDOTIN) 1.25 mg/kg IV over 30 min (max dose: 125 mg for patients ≥100 kg) · Days 1, 8, 15 of each 28-day cycle · IV ✗ Not registered in UA
- Reason
- Provisional current-line default from ALGO-UROTHELIAL-METASTATIC-2L: step 1 did not select a treatment branch. Clinical trial preferred at relapse. Discuss with MDT.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-UROTHELIAL-2L-PEMBROLIZUMAB
- Regimen
- Pembrolizumab monotherapy
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV over 30 min (flat dose) · Day 1 q21d (q3w); or 400 mg q6w (alternative flat dose — equivalent exposure) · IV ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-UROTHELIAL-2L-ERDAFITINIB
- Regimen
- Erdafitinib monotherapy (THOR cohort 1) — 2L+ FGFR2/3-altered metastatic urothelial carcinoma
- Drugs + NSZU
- Erdafitinib (DRUG-ERDAFITINIB) 8 mg PO once daily, with up-titration to 9 mg PO once daily on day 14-21 if serum phosphate <5.5 mg/dL and no significant toxicity · PO daily, continuous (28-day cycle for accounting) · PO ✗ Not registered in UA
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-UROTHELIAL-2L-PLATINUM-CHEMO
- Regimen
- Gemcitabine + carboplatin (urothelial carcinoma, cisplatin-ineligible)
- Drugs + NSZU
- Gemcitabine (DRUG-GEMCITABINE) 1000 mg/m² IV over 30 min · Days 1 and 8 q21d · IV ⚠ NSZU — not for this indication
- Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV over 30 min (Calvert formula: dose [mg] = AUC × [GFR + 25]) · Day 1 q21d (after gemcitabine infusion) · 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
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-CT-CHEST-ABDOMEN-PELVIS | CT chest + abdomen + pelvis with IV contrast | Critical | imaging | — | aggressive |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-CT-CAP | CT chest/abdomen/pelvis | Standard | imaging | — | standard |
| TEST-NGS-COMPREHENSIVE | Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes) | Desired | histology | CSD Lab: M065 | desired (aggressive) |
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-UROTHELIAL-2L-EV)
- Не призначати EV після попереднього EV+пємбролізумаб (відсутno даno про ефективnoсть повторного призначення EV)
- Не пропускати тестування FGFR2/3 перед 2L — FGFR+ пацієнти мають перевагу від ердафітиnoбу (HR 0.58)
- Не призначати при неконтрольованому ЦД — гіперглікемія є значущою токсичnoстю
Standard plan (IND-UROTHELIAL-2L-PEMBROLIZUMAB)
- Не призначати при попередньому ICI лікуванno (авелумаб, пembro, атезолізумаб) — повторне ICI не підтверджено
- Не пропускати FGFR2/3 тестування перед 2L — FGFR+ пацієнти мають кращу відповідь на ердафітиnoб
- Не застосовувати при активних аутоімунних захворюваннях (ГКС >10 мг/д)
Aggressive plan (IND-UROTHELIAL-2L-ERDAFITINIB)
- НЕ призначати без підтвердження FGFR2/3 alteration (Therascreen companion diagnostic OR comprehensive NGS) — generic FGFR overexpression by IHC недостатня.
- НЕ використовувати в PD-(L)1-naive setting — THOR cohort 2 negative vs pembrolizumab.
- НЕ підвищувати дозу до 9 мг без перевірки фосфату на день 14-21 — up-titration лише при phosphate <5.5 мг/дл.
- НЕ ігнорувати baseline + serial офтальмологічний огляд — central serous retinopathy ~25%, often reversible але потребує hold.
- НЕ ігнорувати фосфат моnoторинг — гіперфосфатемія ~76%; дієта + sevelamer; затримка / зниження дози при >7 мг/дл.
- НЕ комбінувати з потужними CYP3A4 OR CYP2C9 інгібіторами / індукторами — експозиція erdafitinib різко змінюється.
- НЕ ігнорувати nail / skin / mucosal care — onycholysis, paronychia, stomatitis високої частоти.
- НЕ підтверджувати план без funding pathway — erdafitinib не зареєстрований в UA (Janssen EAP / named-patient only).
Standard plan (IND-UROTHELIAL-2L-PLATINUM-CHEMO)
- Не призначати при FGFR2/3-позитивному статусі — ердафітиnoб (THOR: PFS HR 0.58; ORR 35% vs 8.5% хімії) — кращий варіант
- Не забути тестування FGFR2/3 ПЕРЕД призначенням — 15-20% UC мають FGFR2/3 альтерацію
- Не призначати цисплатин при GFR <60 мл/хв або Grade ≥2 нейропатії — використовувати карбоплатин
- Не призначати при CrCl <30 мл/хв — карбоплатин протипоказаний
- Не переоцінювати AUC — перераховувати карбоплатин за формулою Кальверта перед КОЖНИМ циклом
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Enfortumab vedotin monotherapy (urothelial carcinoma)
28-day cycles × Until progression or unacceptable toxicity
Aggressive plan
Induction · Erdafitinib monotherapy (THOR cohort 1) — 2L+ FGFR2/3-altered metastatic urothelial carcinoma
28-day cycles × Until progression / unacceptable toxicity
Standard plan
Induction · Gemcitabine + carboplatin (urothelial carcinoma, cisplatin-ineligible)
21-day cycles × 4-6 cycles (until progression, unacceptable toxicity, or complete response)
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-FGFR3-MUTATION
What is the status of FGFR3 mutation/fusion (BIO-FGFR3-MUTATION)? It is required by track(s): IND-UROTHELIAL-2L-ERDAFITINIB. Expected value: FGFR3 activating mutation (S249C, R248C, G370C, Y373C) OR FGFR2 / FGFR3 fusion (THOR-eligible alterations); confirm with Therascreen companion diagnostic OR NGS.
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.
→ molecular_geneticist
MDT talk tree (3 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | molecular_geneticist | Biomarker status | What is the status of FGFR3 mutation/fusion (BIO-FGFR3-MUTATION)? It is required by track(s): IND-UROTHELIAL-2L-ERDAFITINIB. Expected value: FGFR3 activating mutation (S249C, R248C, G370C, Y373C) OR FGFR2 / FGFR3 fusion (THOR-eligible alterations); confirm with Therascreen companion diagnostic OR NGS. |
| 3 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
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.
Owns: OQ-BIOMARKER-FGFR3-MUTATION
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-ENVIRONMENTAL-ARSENIC-WATER-PREVENTION, RF-IATROGENIC-CYCLOPHOSPHAMIDE-LATE-PREVENTION, RF-IATROGENIC-PEDIATRIC-PELVIC-RT-PREVENTION, RF-LIFESTYLE-TOBACCO-CANCER-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-OCC-AROMATIC-AMINES-MALIGNANCY-PREVENTION, RF-OCC-DIESEL-EXHAUST-PREVENTION, RF-OCC-FIREFIGHTER-PREVENTION, RF-OCC-PAH-PREVENTION, RF-OCC-PAINTERS-PREVENTION, RF-SCHISTOSOMA-HAEMATOBIUM-BLADDER-PREVENTION, RF-UROTHELIAL-EV-CONTRAINDICATED, RF-UROTHELIAL-FRAILTY-AGE, RF-UROTHELIAL-HIGH-RISK-BIOLOGY, RF-UROTHELIAL-INFECTION-SCREENING, RF-UROTHELIAL-ORGAN-DYSFUNCTION, RF-UROTHELIAL-TRANSFORMATION-PROGRESSION
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-FGFR3-MUTATION | FGFR3 mutation/fusion | molecular_geneticist | no | IND-UROTHELIAL-2L-ERDAFITINIB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: FGFR3 activating mutation (S249C, R248C, G370C, Y373C) OR FGFR2 / FGFR3 fusion (THOR-eligible alterations); confirm with Therascreen companion diagnostic OR NGS |
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).
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-EAU-BLADDER-2024: EAU Muscle-Invasive Bladder (2024)
- SRC-EV301-POWLES-2021: Enfortumab vedotin in previously treated advanced urothelial carcinoma ()
- SRC-KEYNOTE-045-BELLMUNT-2017: Pembrolizumab as second-line therapy for advanced urothelial carcinoma ()
- SRC-NCCN-BLADDER-2025: NCCN Bladder Cancer (2025.v3)
Experimental options (clinical trials)
Last synced: 2026-09-09 · 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).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Standard plan Enfortumab vedotin monotherapy (urothelial carcinoma) (REG-EV-MONO-UROTHELIAL) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan Pembrolizumab monotherapy (REG-PEMBROLIZUMAB-MONO) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Erdafitinib monotherapy (THOR cohort 1) — 2L+ FGFR2/3-altered metastatic urothelial carcinoma (REG-ERDAFITINIB-UROTHELIAL-2L) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan Gemcitabine + carboplatin (urothelial carcinoma, cisplatin-ineligible) (REG-GEM-CARBO-UROTHELIAL) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-09-09.