346.1 🎓 醫孞生版

346.1.0.1 📌 䞀頁重點

346.1.0.1.1 Renal Cell Carcinoma (RCC)

346.1.1 Epidemiology

  • 90% of adult kidney malignancies
  • M > F (1.5:1)
  • 60-70 yo peak
  • Rising incidence (incidental detection)
  • 5-year survival highly stage-dependent (90%+ localized, < 20% metastatic)

346.1.2 Risk Factors

  • Smoking
  • Obesity
  • Hypertension
  • CKD / dialysis (long-term)
  • Acquired cystic kidney disease
  • Hereditary syndromes:
    • VHL syndrome
    • Hereditary papillary RCC (MET mutations)
    • Hereditary leiomyomatosis RCC (FH mutations)
    • Birt-Hogg-Dubé (FLCN)
    • Tuberous sclerosis
  • Trichloroethylene exposure
  • Pelvic radiation (history)

346.1.3 Pathology

Clear Cell Carcinoma (75%): - VHL gene mutation (loss of tumor suppressor) - 3p deletion - Most common, classical “clear” cytoplasm - Most amenable to targeted + IO therapy

Papillary RCC (10-15%): - Type 1: indolent, MET mutations - Type 2: aggressive, including hereditary

Chromophobe (5%): - Better prognosis - Birt-Hogg-Dubé association

Collecting Duct + Medullary: - Aggressive, rare - Medullary: sickle cell trait, young patients

MiT Family Translocation RCC: - Adolescent / young adult - TFE3, TFEB

Sarcomatoid Features: - Worst prognosis - Various histologic backgrounds

346.1.4 Clinical Presentation

  • Often incidental (50%+) — imaging for other reasons
  • Classic triad (10%): flank pain + hematuria + abdominal mass — late
  • Paraneoplastic syndromes:
    • Erythrocytosis (EPO secretion) — distinctive
    • Hypercalcemia (PTHrP or osteolytic)
    • HTN (renin secretion)
    • Cushing syndrome (ACTH ectopic)
    • Stauffer syndrome (hepatic dysfunction without metastases — IL-6)
    • Anemia (chronic disease)
  • Symptomatic metastases: bone pain, dyspnea (lung mets), neuro (brain)

346.1.5 Diagnosis

  • CT with contrast (3-phase) — characterize mass
  • MRI alternative
  • Biopsy NOT routinely (risk + reliability) — diagnosis often after nephrectomy
  • Stage: TNM (8th edition)
  • Workup: CT chest, brain MRI if symptoms, bone scan, LFT, LDH

346.1.6 Localized Disease Treatment

Surgery: - Partial nephrectomy (preferred when feasible — preserves kidney function) - Radical nephrectomy (large, central, complex) - Open, laparoscopic, robotic - Active surveillance for small masses (< 4 cm) in elderly / poor surgical candidates

Adjuvant Therapy: - Pembrolizumab (KEYNOTE-564) — adjuvant for high-risk after surgery; FDA approved 2021 - Improves DFS

Ablation: cryoablation, RFA for small tumors in elderly / unfit

346.1.7 Metastatic RCC Treatment

First-Line IO + TKI Combinations (Practice-Changing 2018-2024):

Cabozantinib + Nivolumab (CheckMate 9ER, 2020): - TKI (VEGFR + MET + AXL) + anti-PD-1 - Median PFS 17 months - Approved

Pembrolizumab + Axitinib (KEYNOTE-426, 2019): - Anti-PD-1 + VEGFR TKI - Median PFS 15.7 months - Approved

Pembrolizumab + Lenvatinib (CLEAR, 2021): - Anti-PD-1 + VEGFR TKI - Median PFS 23.9 months (longest in trials)

Nivolumab + Ipilimumab (CheckMate 214): - Intermediate-poor risk - Median PFS 11.6 months - Better OS than sunitinib

Single Agent TKIs (Historical, Specific Settings): - Sunitinib, pazopanib, axitinib, cabozantinib, lenvatinib, tivozanib - Bevacizumab (anti-VEGF) - Temsirolimus (mTOR for poor-risk)

Second-Line + Beyond: - Cabozantinib (METEOR) - Tivozanib - Other TKIs - Lenvatinib + everolimus - Belzutifan (HIF-2α inhibitor, FDA 2021 for VHL, expanding)

346.1.8 Belzutifan (HIF-2α Inhibitor)

  • For VHL-associated RCC
  • LITESPARK-001/004: phase 2/3
  • LITESPARK-005 (2023): vs everolimus in second-line — improved PFS
  • FDA approval 2021 (VHL)

346.1.9 Hereditary RCC Surveillance

  • VHL syndrome: surveillance imaging
  • HPRC: lifelong
  • HLRCC: aggressive screening + early surgery
  • BHD: skin findings + lung cysts
346.1.9.0.1 Bladder Cancer

346.1.10 Epidemiology

  • ~ 80,000 new cases/year US
  • M > F (3:1)
  • 65 yo peak
  • 4th most common male cancer

346.1.11 Risk Factors

  • Smoking (top — 50-60% of cases)
  • Occupational (aromatic amines: dye, rubber, leather, textile industries)
  • Chronic UTI / cystitis
  • Schistosoma haematobium (squamous cell carcinoma)
  • Radiation
  • Cyclophosphamide
  • Aristolochic acid (䞭草藥)
  • Pelvic radiation

346.1.12 Pathology

Urothelial Carcinoma (Transitional Cell, 90%): - Most common - Smoking-related - Field defect (recurrence common) - Can be in renal pelvis, ureter, bladder, urethra

Squamous Cell Carcinoma (5%): - Schistosoma haematobium (Egypt, Africa) - Chronic inflammation / catheterization

Adenocarcinoma (1-2%): - Urachal remnant - Chronic inflammation

Small Cell Carcinoma (rare): aggressive

Other: micropapillary, sarcomatoid, plasmacytoid

346.1.13 Clinical Presentation

  • Painless gross hematuria (80%) — hallmark
  • Microscopic hematuria
  • Voiding symptoms (dysuria, frequency)
  • Late: pelvic pain, flank pain (UTUC + obstruction)

346.1.14 Diagnosis

  • Cystoscopy (gold standard)
  • Urine cytology (good for high-grade)
  • Imaging: CT urography (assess upper tract + lymph nodes)
  • TURBT (transurethral resection of bladder tumor): diagnostic + therapeutic

346.1.15 Staging

  • TNM (8th edition)
  • Non-muscle invasive (NMIBC):
    • Tis (carcinoma in situ)
    • Ta (non-invasive papillary)
    • T1 (lamina propria invasion)
  • Muscle invasive (MIBC):
    • T2-T4 (muscularis + beyond)

346.1.16 Risk Stratification (NMIBC)

  • Low risk: small, papillary, low-grade
  • Intermediate: larger, multiple, recurrent
  • High risk: high-grade, T1, multifocal, CIS

346.1.17 Treatment

Non-Muscle Invasive (NMIBC):

TURBT (complete resection) - Often repeat - Reassess depth

Intravesical Therapy: - BCG (immunotherapy): for high-risk; gold standard - Mitomycin C (chemotherapy): single dose post-TURBT for low-risk - Gemcitabine, valrubicin alternatives - Pembrolizumab (KEYNOTE-057) — for BCG-unresponsive CIS

Recurrence: re-TURBT + alternate intravesical

BCG-Refractory: - Pembrolizumab (KEYNOTE-057) - Cystectomy - Nadofaragene firadenovec (gene therapy)

Muscle Invasive (MIBC):

Radical Cystectomy + Lymph Node Dissection: - Standard of care - Urinary diversion (neobladder, ileal conduit, continent diversion) - Multidisciplinary

Neoadjuvant Chemotherapy: - Cisplatin-based (MVAC, GC, dose-dense MVAC) - Before cystectomy for cisplatin-eligible - Improves OS

Bladder Preservation: - TURBT + chemoradiation - For selected patients - Tri-modality therapy

Adjuvant: - Nivolumab (CheckMate 274) — adjuvant immunotherapy post-cystectomy or chemoradiation - FDA approved

Locally Advanced + Metastatic:

Cisplatin-Based Chemotherapy (Cisplatin-Eligible): - GC (gemcitabine + cisplatin) - MVAC (methotrexate + vinblastine + doxorubicin + cisplatin)

Cisplatin-Ineligible: - Pembrolizumab or atezolizumab (PD-L1+) - Gem + carbo

Maintenance: - Avelumab maintenance (JAVELIN Bladder 100, 2020) — after chemo

Newer Agents:

Enfortumab Vedotin (EV) — Nectin-4 ADC: - For pretreated platinum + IO

EV-302 (2024) — Pembrolizumab + EV First-Line: - Paradigm-shifting - Improved OS vs chemotherapy - ~ 2x improvement in median OS - Practice-changing for advanced bladder

Erdafitinib (Balversa) — FGFR3 inhibitor: - FGFR2/3 alterations - Approved 2019

Sacituzumab Govitecan — Trop-2 ADC: - Pretreated - Approved

346.1.17.0.1 Other Urologic Malignancies

346.1.18 Prostate Cancer

  • Most common male cancer in many countries
  • PSA screening (controversial; USPSTF 50-69 individualized)
  • Localized: surgery, RT, active surveillance
  • Advanced: ADT + abiraterone / enzalutamide / apalutamide / docetaxel + PARP inhibitor (BRCA mutations)
  • See appropriate cancer textbook chapter

346.1.19 Testicular Cancer

  • Young men (15-35 yo)
  • Highly curable (95%+ with multimodal)
  • Germ cell tumors (seminoma + NSGCT)
  • Inguinal orchiectomy + chemo (BEP)
  • See appropriate cancer textbook chapter

346.1.20 Upper Tract Urothelial Carcinoma (UTUC)

  • Ureter, renal pelvis
  • 5-10% of urothelial cancers
  • Lynch syndrome association
  • Nephroureterectomy (segmental for low-risk distal)
  • Adjuvant chemo (POUT trial)

346.1.21 Wilms Tumor

  • Pediatric (most common renal cancer in kids)
  • Excellent prognosis
  • Multimodal therapy
346.1.21.0.1 Special Topics

346.1.22 VHL Syndrome

  • Multiple organ involvement:
    • Renal cysts + clear cell RCC
    • CNS hemangioblastoma
    • Pheochromocytoma
    • Retinal hemangioblastoma
    • Pancreatic + epididymal cystadenoma
  • Belzutifan for tumors

346.1.23 Acquired Cystic Kidney Disease + RCC

  • ESKD + long-term dialysis
  • Multiple cysts
  • ↑ RCC risk
  • Screening considered

346.1.24 Hematuria Workup

  • Gross or persistent microscopic
  • Cystoscopy + CT urography + cytology
  • AUA guidelines based on age + risk factors

346.1.25 Bladder Cancer Surveillance Post-Treatment

  • Cystoscopy intervals
  • Urine cytology
  • Imaging
  • Risk-adapted

346.1.25.1 🩺 床邊速查

  • RCC: 90% adult kidney malignancy; clear cell (75%, VHL)
  • RCC presentation: incidental (50%), classic triad (10%)
  • RCC paraneoplastic: erythrocytosis (EPO), hypercalcemia, HTN, Stauffer
  • Bladder cancer: urothelial 90%; painless gross hematuria 80%
  • NMIBC: TURBT + intravesical BCG / chemo / IO (pembrolizumab for BCG-unresponsive)
  • MIBC: radical cystectomy + neoadjuvant cisplatin chemo
  • EV-302 (2024): enfortumab vedotin + pembrolizumab paradigm-shifting first-line advanced
  • Belzutifan (HIF-2α) for VHL RCC (FDA 2021)
  • Schistosoma + squamous bladder cancer