RB1 alterations (deletion, mutation) occur in ~30% of muscle-invasive bladder cancer (MIB...
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | BMA-RB1-UROTHELIAL |
|---|---|
| Тип | Клінічна застосовність |
| Статус | переглянуто 2026-05-04 | очікує клінічного підпису | потрібне рев’ю клінічної застосовності |
| Хвороби | DIS-UROTHELIAL |
| Джерела | SRC-EAU-BLADDER-2024 SRC-NCCN-BLADDER-2025 |
Дані про клінічну застосовність
| Біомаркер | BIO-RB1 |
|---|---|
| Варіант | RB1 loss in muscle-invasive urothelial carcinoma (basal/squamous-differentiated subtype enrichment; CDK4/6i resistance marker; no approved RB1-directed therapy) |
| Хвороба | DIS-UROTHELIAL |
| Рівень ESCAT | IIIB |
| Рекомендовані комбінації | 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) |
| Протипоказана монотерапія | CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) — inactive in RB1-null context; not approved for bladder cancer and biologically ineffective without pRb |
| Підсумок доказів | 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. |
Нотатки
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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