Alterações RB1 (suppressione, mutação) ocorrem em ~30% do câncer de bexiga invasiva muscular (MIB...
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| ID | BMA-RB1-UROTHELIAL |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-UROTHELIAL |
| Fontes | SRC-EAU-BLADDER-2024 SRC-NCCN-BLADDER-2025 |
Fatos de ação
| Biomarcador | BIO-RB1 |
|---|---|
| Variante | Perda de RB1 no carcinoma urotelial invasivo muscular (enriquecimento de subtipos diferenciados pelo baso/escumoso; marcador de resistência CDK4/6i; não houve terapêutica aprovada direcionada pelo RB1) |
| Doença | DIS-UROTHELIAL |
| Nível ESCAT | IIIB |
| Combinações recomendadas | Platinum-based neoadjuvant chemotherapy (gemcitabine + cisplatin × 4 cycles prior to radical cystectomy) — standard for MIBC regardless of RB1 status; basal/squamous subtype (often RB1-low) may have enhanced sensitivity, Pembrolizumab or atezolizumab — approved for urothelial carcinoma (not RB1-specific; PD-L1 and TMB guide selection) |
| Contraindicated monotherapy | Inibidores CDK4/6 (palbociclib, ribociclib, abemaciclib) — inativos no contexto RB1-null; não aprovados para cancro da bexiga e biologicamente ineficaz sem pRb |
| Resumo das provas | RB1 alterations (deletion, mutation) occur in ~30% of muscle-invasive bladder cancer (MIBC) and are enriched in the basal/squamous-differentiated molecular subtype (~50%). RB1 loss is associated with resistance to CDK4/6 inhibitors (which require pRb to exert G1 arrest). In urothelial cancer, CDK4/6 inhibitors are investigational (no approved indication); however, RB1 status is being evaluated as a predictive biomarker for CDK4/6 inhibitor non-response in HR+ cancers where bladder patients are enrolled in basket trials. Therapeutic implications in bladder cancer: (1) RB1 loss may associate with sensitivity to immunotherapy (higher genomic instability) — inconsistent evidence; (2) Basal/squamous subtype (often RB1-low) responds better to neoadjuvant chemotherapy than luminal subtypes; (3) No approved targeted therapy exploits RB1 deficiency in bladder cancer as of 2026. ESCAT IIIB: RB1 is a prognostic and potential therapeutic vulnerability marker in urothelial cancer; no approved targeted agent. |
Notas
ESCAT IIIB: RB1 loss in urothelial cancer marks the basal/squamous subtype (along with CD44+, CK5/6+, CK14+) which has distinct biology from luminal subtypes. Key clinical implication: in the context of bladder cancer molecular subtyping, RB1-low/basal tumors appear to have more favorable responses to neoadjuvant cisplatin-based chemotherapy (paradoxically better despite poorer prognosis at diagnosis). This has not led to a specific approved biomarker-driven therapy. Watch for: EV-302/KEYNOTE-A39 trial (enfortumab vedotin + pembrolizumab, regardless of molecular subtype) has largely supplanted subtype-based treatment decisions in 1L metastatic urothelial cancer.
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