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

Demographics

• 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)

Diagnosis

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

Treatment

Medications

• 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 ...