Overview:

• RCC is the most common kidney cancer (~90% of cases), arising from the renal tubular epithelium.
• Clear cell RCC (ccRCC) is the most common subtype (~75–80%).
• Other subtypes: papillary, chromophobe, collecting duct, translocation RCC.

Risk Factors:

• Smoking, obesity, hypertension
• Male sex, older age
• Genetic syndromes (e.g., von Hippel–Lindau)
• Chronic kidney disease, dialysis

Clinical Features:

• Classic triad (rare): Flank pain, hematuria, abdominal mass
• Often incidental finding on imaging
• May present with metastatic disease (~30% at diagnosis)

Staging:

• Based on TNM system
• Localized (Stage I–II), locally advanced (Stage III), or metastatic (Stage IV)

Treatment Overview:

1. Localized RCC (Stage I–III):

• Surgery (partial or radical nephrectomy) is curative in most cases
• Active surveillance for small, indolent tumors in select patients

2. Metastatic RCC (Stage IV):

• Systemic therapy is the mainstay

A. First-line Options:

• Combination Immunotherapy:
  • Nivolumab + Ipilimumab (preferred for intermediate/poor-risk)
  • Pembrolizumab + Axitinib
  • Cabozantinib + Nivolumab
  • Lenvatinib + Pembrolizumab

B. Targeted Therapy (TKIs):

• Cabozantinib, Axitinib, Lenvatinib, Sunitinib, Pazopanib

C. mTOR Inhibitors:

• Everolimus – used less frequently now (e.g., post-TKI or IO)

D. Cytokine Therapy:

• High-dose IL-2 – rarely used today due to toxicity and newer options