346.4 📋 章末速蚘 Summary

346.4.1 🔑 䞀句話瞜結

Urologic malignancies 涵蓋(1) renal cell carcinoma (RCC) — 90% adult kidney malignancyclear cell most common (75%, VHL gene) + papillary (10-15%, MET type 1) + chromophobe (5%, BHD) + medullary (aggressive, sickle cell trait) + MiT family (young) + sarcomatoid (worst)RCC risk factorssmoking + obesity + HTN + CKD/dialysis + hereditary (VHL, HPRC, HLRCC, BHD, TSC)RCC presentationoften incidental (50%) + classic triad rare (10%) + paraneoplastic syndromes (erythrocytosis EPO, hypercalcemia PTHrP, HTN renin, Stauffer hepatic dysfunction without mets, anemia)localized RCCpartial nephrectomy preferred + adjuvant pembrolizumab (KEYNOTE-564 2021) for high-riskmetastatic RCCIO + TKI combinations practice-changing — pembrolizumab + lenvatinib (CLEAR, longest PFS), cabozantinib + nivolumab (CheckMate 9ER), pembrolizumab + axitinib (KEYNOTE-426), nivolumab + ipilimumab (CheckMate 214 intermediate-poor); belzutifan (HIF-2α inhibitor, LITESPARK-005, FDA 2021) for VHL RCC + select sporadic(2) bladder cancerurothelial 90% > squamous (schistosomiasis) > adenocarcinomasmoking #1 risk + occupational (aromatic amines) + schistosoma + aristolochic acidpainless gross hematuria 80% classicaldiagnose with cystoscopy + cytology + CT urographyNMIBC → TURBT + intravesical BCG (high-risk) / mitomycin (low-risk) / pembrolizumab (KEYNOTE-057 BCG-unresponsive)MIBC → radical cystectomy + neoadjuvant cisplatin chemo + adjuvant nivolumab (CheckMate 274)metastatic 2024 paradigm-shiftEV-302 enfortumab vedotin + pembrolizumab first-line (OS 31.5 vs 16.1 months chemo); cisplatin-based chemo + maintenance avelumab (JAVELIN Bladder 100) for cisplatin-eligible non-progressors; erdafitinib for FGFR3 alterations; sacituzumab govitecan (Trop-2 ADC)(3) upper tract urothelial carcinoma (UTUC): Lynch syndrome + aristolochic acid; nephroureterectomy。

346.4.2 💊 治療粟芁

  • localized RCCpartial nephrectomy (preferred) > radical nephrectomy; ablation for elderly small tumors; adjuvant pembrolizumab (KEYNOTE-564) high-risk
  • metastatic RCC first-line IO+TKI combospembrolizumab + lenvatinib (CLEAR — best PFS) OR cabozantinib + nivolumab (CheckMate 9ER) OR pembrolizumab + axitinib (KEYNOTE-426) OR nivolumab + ipilimumab (CheckMate 214 — intermediate/poor risk)
  • VHL-associated RCCbelzutifan (HIF-2α inhibitor, FDA 2021, LITESPARK-005)
  • NMIBCTURBT + intravesical BCG (high-risk, gold standard) or mitomycin (low-risk single dose); pembrolizumab (KEYNOTE-057) for BCG-unresponsive CIS
  • MIBCneoadjuvant cisplatin (GC, dose-dense MVAC) + radical cystectomy + LN dissection + adjuvant nivolumab (CheckMate 274); bladder preservation tri-modality alternative (TURBT + chemoradiation)
  • metastatic urothelial 2024EV-302 enfortumab vedotin (Nectin-4 ADC) + pembrolizumab first-line (OS 31.5 vs 16.1 mo chemo) — practice-changing
  • cisplatin-eligible advanced urothelialGC or MVAC chemo + maintenance avelumab (JAVELIN Bladder 100)
  • FGFR3-altered urothelialerdafitinib (Balversa, FDA 2019)
  • second-line metastatic urothelialenfortumab vedotin, sacituzumab govitecan
  • UTUCnephroureterectomy (gold standard) ± adjuvant chemo (POUT trial)

346.4.3 🎯 盧醫垫的考前提醒

  1. RCC clear cell 75% + VHL gene mutationmost common subtype + most amenable to targeted + IO therapypapillary 10-15% (MET in type 1), chromophobe 5% (BHD), medullary aggressive (sickle cell trait association)
  2. RCC paraneoplastic syndromes 經兞erythrocytosis (EPO secretion), hypercalcemia (PTHrP), HTN (renin), Cushing (ACTH ectopic), Stauffer syndrome (hepatic dysfunction without metastases — IL-6 driven, resolves with nephrectomy), anemia
  3. RCC classic triad (flank pain + hematuria + abdominal mass) only 10% — late stage; 50% incidental detection on imaging for other reasons
  4. metastatic RCC IO+TKI combinations standard 2018-2024CLEAR (pembrolizumab + lenvatinib — longest PFS 23.9 mo) + CheckMate 9ER (cabozantinib + nivolumab) + KEYNOTE-426 (pembrolizumab + axitinib) + CheckMate 214 (nivolumab + ipilimumab for intermediate/poor risk)
  5. adjuvant pembrolizumab RCC KEYNOTE-564 (2021) — FDA approved for high-risk after surgery
  6. belzutifan (Welireg) HIF-2α inhibitorVHL-associated RCC FDA 2021 + LITESPARK-005 (2023) for sporadic RCC second-line > everolimus
  7. bladder cancer urothelial 90% + painless gross hematuria 80% classical + smoking #1 risk factor + occupational (aromatic amines: dye, rubber, leather, textile)
  8. schistosoma haematobium → squamous cell bladder carcinomaEgypt, Africa endemic; chronic inflammation drives squamous transformation
  9. NMIBC intravesical BCGgold standard for high-risk + CIS; pembrolizumab (KEYNOTE-057) for BCG-unresponsive alternative to cystectomy
  10. EV-302 (2024) paradigm-shifting for metastatic urothelialenfortumab vedotin (Nectin-4 ADC) + pembrolizumab first-line doubles OS (31.5 vs 16.1 months chemo) — new standard