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For further information, see CMDT Part 39-20: Renal Cell Carcinoma

Key Features

Essentials of Diagnosis

  • Gross or microscopic hematuria

  • Flank pain or mass in some patients

  • Systemic symptoms such as fever, weight loss may be prominent

  • Solid renal mass on imaging

General Considerations

  • ~2.6% of all adult cancers

  • In the United States, ~62,700 cases of renal cell carcinoma are diagnosed and 14,240 deaths result annually


  • Peak incidence in sixth decade of life

  • Male-to-female ratio = 2:1

  • Risk factors: physical inactivity, obesity, and diabetes mellitus

  • Cigarette smoking is the only known significant environmental risk factor

  • Familial: von Hippel-Lindau syndrome, hereditary papillary renal cell carcinoma, hereditary leiomyoma-renal cell carcinoma, Birt-Hogg-Dube syndrome

  • Association: dialysis-related acquired cystic disease

Clinical Findings

Symptoms and Signs

  • Hematuria (gross or microscopic) in 60% of cases

  • Flank pain or an abdominal mass in ~30%

  • Triad of flank pain, hematuria, and mass in ~10–15%, often a sign of advanced disease

  • Fever occurs as a paraneoplastic symptom

  • Symptoms of metastatic disease (cough, bone pain) in ~20–30% at presentation

  • Often detected incidentally

Differential Diagnosis

  • Angiomyolipomas (fat density usually visible by CT)

  • Renal pelvis urothelial cancers (more central location, involvement of the collecting system, positive urinary cytology)

  • Renal oncocytomas (indistinguishable from renal cell carcinoma preoperatively)

  • Renal abscesses

  • Adrenal tumors (superoanterior to the kidney)


Laboratory Tests

  • Hematuria in 50%

  • Paraneoplastic syndromes

    • Erythrocytosis from increased erythropoietin production in ~5% (but anemia is far more common)

    • Hypercalcemia in 10%

    • Stauffer syndrome, a reversible syndrome of hepatic dysfunction

Imaging Studies

  • Solid renal masses on abdominal ultrasonography or CT

  • CT and MRI scanning are the most valuable imaging tests; they confirm character of the mass, stage the lesion

  • Chest radiographs for pulmonary metastases

  • Bone scans for large tumors, bone pain, elevated alkaline phosphatase levels

  • Brain imaging should be obtained in patients with high metastatic burden or in those with neurologic deficits



  • For metastatic renal cell carcinoma, no effective cytotoxic chemotherapy is available

  • Vinblastine yields short-term partial response rates of 15%

  • Bevacizumab can prolong time to progression in persons with metastatic disease (Table 39–2)

  • Biologic response modifiers: α-interferon yields partial response rate of 15–20% and interleukin-2, partial response rate of 15–35%

  • Vascular endothelial growth factor (VEGF) and Raf-kinase inhibitors: oral agents, well-tolerated, with demonstrated effectiveness in patients with advanced kidney cancer, especially clear cell carcinoma (~40–60% response rate); agents include

    • Sunitinib

    • Pazopanib

    • Cabozantanib

    • Axitinib

    • Sorafanib

  • Sunitinib has been approved for adjuvant use after complete surgical resection in patients with adverse pathological features

  • Everolimus and temsirolimus are ...

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