Renal Cell Carcinoma 8/21/2018

Narges presented an unfortunate case of a young woman in her 20s who presented with worsening abdominal pain, nausea, and vomiting 8 days after a lap-chole for biliary cholic, found to have metastatic renal cell carcinoma in the absence of any risk factors.

Renal Cell Carcinoma

  • Epidemiology:
    • Most common primary malignant renal tumors (90-95%)
    • M > F (3:2)
    • Median age of onset: 50-70
  • Risk Factors
    • Obesity
    • Smoking (doubles risk)
    • Von-Hippel Lindau (Up to 2/3 of patients with VHL! Clear cell RCC)
    • Acquired cystic kidney disease (long term dialysis), 30x increase
    • Exposure: Asbestos, cadmium, leather tanning or petroleum industrial¬† products
  • Presentation
    • Usually asx until late stage
    • B Sx
    • Most common finding = gross or microscopic hematuria
    • Men: Left sided varicocele, anatomic obstruction of testicular vein
    • Flank pain, FUO, mass, hypertension, edema, liver dysfunction (Stauffer syndrome)
    • Paraneoplastic: 20% of cases
      • Erythrocytosis (inc erythropoietin)
      • Anemia (weird right?)
      • Hypercalcemia
      • Secondary (AA) amyloidosis
    • Diagnosis
      • CT w/ con or MRI
      • Renal mass that is enhanced by contrast strongly suggests RCC
      • Smaller lesions: biopsy, larger lesions: partial nephrectomy
    • Management
      • 5 year survival, once metastatic, is around 8%
      • Early: Partial or radical nephrectomy can be curative
        • If localized within renal vein involvement: resection is curative, no role for adjuvant therapy.
      • Advanced: Depends! If metastatic to only adrenal gland, radical nephrectomy still potentially. Otherwise tx is palliative. Traditional cytotoxic chemo has not been found to be helpful. Systemic immunotherapy and tumor debulking (as much as possible). A study published in NEJM in 2001 found that nephrectomy prior to chemo improves survival (11.1 vs 8.1 months), study drug was inferferon alfa though.
        • Radiation: No role in management
        • “Conventional” cytotoxic chemo: Not shown to be helpful
        • Anti VEGF
          • Sunitinib (tyrosine kinase inhibitor)
          • Bevacizumab (anti-VEGF MAB)
          • Used for advanced metastatic disease but no role in adjuvant therapy
        • PD1: Phase III trial in 2017, combination of Nivolumab + Ipilimumab is superior vs Sunitinib
          • 18 month survival: 75% vs 60%
        • mTOR inhibitors
          • Temsirolimus
          • Everolimus
      • Commonly asked complications:
        • Higher incidence of spontaneous intracranial hemorrhage with metastatic RCC to the brain, be careful with anticoagulation but this is not an absolute contraindication. Individualized decision!
        • Paper published in 2015 in Blood, retrospective cohort study, 293 pts with brain mets. Sub-group analyses showed 4x inc in intracranial hemorrhage of metastatic melanoma and RCC, but not influenced by administration of therapeutic dose of Lovenox.