Kidney Cancer

Genetics:

• Consider VHL, Tuberous sclerosis, Birt-Hogg-Dube (spontaneous pneumothorax is a hallmark)

• Genetic testing in patients with: Multiple renal masses, bilateral or multifocal tumors, diagnosis age < 45, family history of RCC (more than one first/second degree relatives with RCC)

Types:

• Clear cell RCC: 75%

• Non-Clear Cell RCC: 25%

  • Papillary RCC is associated with MET mutation. 

• Collecting Duct RCC

• Chromophobe RCC

  • Associated with Birt-Hogg-Dube

• Medullary RCC

  • Associated with sickle cell trait

Clear Cell Renal Cell Carcinoma

Treatment:

• Stage I:

  • T1a and T1b (size < 7cm): Nephron sparing partial nephrectomy (preferred)

  • Size < 3cm: Consider radiofrequency ablation

• Stage II or III:

  • Partial or radical nephrectomy

  • Consider adjuvant pembrolizumab x1 year if high risk (Keynote-564)

    • High risk features:

      • pT2 with WHO G4 or sarcomatoid features

      • stage III (pT3/4)

      • N1

      • stage IV oligometastatic disease with metastasectomy NED

• Stage IV metastatic:

  • Risk stratify with IMDC or MSKCC criteria (1-2 intermediate risk, 3+ poor risk):

    • IMDC: <1 year from diagnosis to systemic therapy, Karnofsky PS <80%, Anemia (Hb <12), Hypercalcemia, Neutrophilia, Thrombocytosis

    • MSKCC: <1 year from diagnosis to treatment, Karnofsky PS <80%, LDH >1.5 ULN, Hypercalcemia, Hb LLN

  • Low risk:

    • They will NOT ask you to pick between IO + TKI options

    • Oligometastatic disease:

      • Nephrectomy + metastasectomy

      • Nephrectomy + SBRT

    • Pembrolizumab+Axitinib (Keynote-426)

    • Pembrolizumab+Lenvatinib (CLEAR)

    • Cabozantinib+Nivolumab (Checkmate-9ER)

  • Intermediate/Poor risk:

    • Pembrolizumab+Axitinib

    • Pembrolizumab+Lenvatinib

    • Cabozantinib+Nivolumab

    • Dual IO: Ipi+Nivo

    • NOT triple therapy (Ipi+Nivo+Cabo) per COSMIC-313 trial

  • Second Line

    • IO if Naive

    • Cabozantinib

    • Axitinib

    • Pazopanib

    • Tivozanib (after at least 2 prior lines of therapy)

    • Everolimus

    • Belzutifan: HIF-alpha inhibitor

      • Side effects: Hypoxia, Anemia

    • Lenvatinib/Everolimus

    • Sunitinib

    • Bevacizumab

    • High-dose IL-2

    • Temsirolimus

  
  

Non-Clear Cell Renal Cell Carcinoma

First line:

• Clinical trial

• Cabozantinib

Also can consider:

• Lenvatinib + Everolimus

• Nivolumab

• Nivolumab + Cabozantinib

• Pembrolizumab

• Sunitinib

  
  

Sarcomatoid RCC

Treatment:

• Ipi + Nivolumab

Medullary Renal Carcinoma

Treatment:

• Carboplatin + Gemcitabine

• Carboplatin + Paclitaxel

• Cisplatin + Gemcitabine

• Gemcitabine + Doxorubicin