346.3 🏥 內科專科考前版

346.3.1 Mechanistic Deep Dive

346.3.1.1 VHL Tumor Suppressor

  • Targets HIF-α for degradation (normoxia)
  • VHL loss → HIF-α stable → VEGF + angiogenesis
  • Target for HIF-2α inhibitor (belzutifan)

346.3.1.2 Nectin-4 in Urothelial Cancer

  • Adhesion molecule
  • Highly expressed
  • Target for enfortumab vedotin (Nectin-4 ADC)

346.3.1.3 Trop-2 in Urothelial

  • Trophoblast cell surface antigen
  • Target for sacituzumab govitecan (ADC)

346.3.2 Recent Trials & Updates

346.3.2.1 EV-302 (2024) — Practice-Changing Bladder

  • N = 886 advanced urothelial carcinoma
  • Enfortumab vedotin + pembrolizumab vs chemotherapy (gemcitabine + cisplatin or carboplatin)
  • Improved OS (median 31.5 vs 16.1 months)
  • Improved PFS
  • FDA approved 2024
  • New first-line standard

346.3.2.2 LITESPARK-005 (2023) — Belzutifan

  • VHL-associated RCC + sporadic RCC
  • Second-line vs everolimus
  • ↑ PFS

346.3.2.3 CheckMate 274 (2021) — Adjuvant Nivolumab MIBC

  • Post-radical cystectomy / chemoradiation
  • ↑ DFS

346.3.2.4 KEYNOTE-564 (2021) — Adjuvant Pembrolizumab RCC

  • ↑ DFS

346.3.2.5 JAVELIN Bladder 100 (2020)

  • Avelumab maintenance after chemo

346.3.2.6 CLEAR (2021) — Lenvatinib + Pembrolizumab

  • Longest median PFS (23.9 months)
  • New standard combination

346.3.3 High-Yield Specialist Points

346.3.3.1 Stauffer Syndrome

  • Hepatic dysfunction in RCC without metastases
  • Elevated alkaline phosphatase + transaminases
  • Resolves with nephrectomy
  • IL-6 driven

346.3.3.2 Erythrocytosis in RCC

  • Ectopic EPO production
  • High Hgb / Hct
  • May normalize with treatment
  • Watch for hyperviscosity

346.3.3.3 Hypercalcemia in RCC

  • PTHrP secretion
  • Osteolytic metastases
  • Treatment: bisphosphonates, denosumab; IV fluids; calcitonin acute

346.3.3.4 Nivolumab + Ipilimumab in Intermediate-Poor Risk RCC

  • CheckMate 214
  • More durable responses
  • Some long-term survivors

346.3.3.5 IO + TKI Selection

  • Patient-specific
  • Performance status
  • Comorbidities
  • Specific TKI side effects
  • Drug interactions

346.3.3.6 Partial vs Radical Nephrectomy

  • Partial: smaller, less complex tumors
  • Renal function preservation
  • Equivalent oncologic outcomes for stage I

346.3.3.7 Active Surveillance Small Renal Masses

  • < 4 cm
  • Elderly / unfit for surgery
  • Growth rate < 0.3 cm/year typical
  • Imaging-based surveillance

346.3.3.8 Cisplatin Eligibility

  • Performance status
  • Renal function (eGFR > 50-60 typical)
  • Hearing
  • Neuropathy
  • Cardiac function

346.3.3.9 BCG Mechanism

  • Live attenuated TB strain
  • Local immune activation
  • Intravesical T-cell response
  • Standard for high-risk NMIBC

346.3.3.10 Erdafitinib for FGFR-Altered Urothelial

  • ~ 20% of urothelial carcinomas have FGFR3 mutations or fusions
  • Selective oral inhibitor
  • FDA approved 2019

346.3.3.11 Lynch Syndrome + UTUC

  • ↑ Risk
  • Genetic counseling
  • Surveillance

346.3.3.12 Wilms Tumor

  • WT1, β-catenin mutations
  • Triphasic histology (blastemal, epithelial, stromal)
  • Highly curable
  • Multimodal (surgery + chemo ± radiation)

346.3.3.13 Active Surveillance Prostate Cancer

  • For low-risk
  • PSA + imaging + biopsy
  • Selected men

346.3.3.14 Cancer Survivorship

  • Long-term monitoring
  • CV risk
  • Secondary cancers
  • Quality of life

346.3.4 Pearls

  • RCC clear cell 75%, VHL
  • Paraneoplastic: erythrocytosis, hypercalcemia, HTN, Stauffer
  • Localized RCC: partial nephrectomy + adjuvant pembrolizumab (KEYNOTE-564)
  • Metastatic RCC: IO + TKI combinations (CLEAR, CheckMate 9ER, KEYNOTE-426, CheckMate 214)
  • Belzutifan for VHL RCC
  • Bladder cancer: painless gross hematuria + smoking + schistosoma (squamous)
  • NMIBC: TURBT + intravesical BCG; pembrolizumab for BCG-unresponsive
  • MIBC: radical cystectomy + neoadjuvant cisplatin + adjuvant nivolumab
  • Metastatic urothelial 2024: EV-302 enfortumab vedotin + pembrolizumab first-line paradigm-shifting