Renal Cell Carcinoma

Source: Walko CM, La-Beck NM, Walsh MD. Renal Cell Carcinoma. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. http://accesspharmacy.com/content.aspx?aid=8011227. Accessed August 6, 2012.

• Malignant tumor of kidney

• Genetic factors contribute to 15% of cases of renal cell carcinoma (RCC); remaining 85% believed to be sporadic.

• Clear cell RCC
  • Predominant subtype responsible for most cases.
  • Affects proximal tubule.
  • Likely to metastasize.
  • Results from inactivation of von Hippel-Lindau (VHL) tumor suppressor gene on chromosome 3p25.
    • Leads to increased production of growth factors, including:
      • Vascular endothelial growth factor (VEGF)
      • Transforming growth factor (TGF)
      • Platelet-derived growth factor (PDGF), as well as others responsible for angiogenesis and cell growth
• Papillary RCC types 1 and 2
  • Occur in proximal tubule.
  • Account for 5–10% of RCC cases.
  • More favorable prognosis than clear cell.
    • Prognosis with type 1 better than type 2.
  • Associated with multiple genetic abnormalities.
• Chromophore and oncocytoma subtypes
  • Occur in intercalated cells of collecting system.
  • Account for 5–10% of RCC cases
  • Associated with wide variety of chromosomal abnormalities.
  • Oncocytomas relatively benign and rarely metastasize.

• Fifth most common cancer in men; sixth most common in women.

• Smoking
• Obesity
• Hypertension

• Most cases diagnosed incidentally following computed tomography (CT) scans done for unrelated reasons.

Signs and Symptoms

• Classic triad symptoms, seen in <10% of patients:
  • Flank pain
  • Hematuria
  • Palpable abdominal mass
• Other presenting symptoms are:
  • Fatigue
  • Weight loss
  • Anemia
  • Hypertension
  • Fever
  • Lower extremity edema
• Metastatic disease symptoms:
  • Bone pain
  • Adenopathy
  • Pulmonary

Means of Confirmation and Diagnosis

• Results from biopsy

Laboratory Tests

• Complete blood count (CBC)
• Metabolic panel
• Lactate dehydrogenase
• Coagulation profile
• Urinalysis

Imaging

• CT: contrast and noncontrast of chest, abdomen, and pelvis or
• MRI of chest, abdomen, and pelvis

Diagnostic Procedures

• Biopsy of surgical specimen

Staging

• Tumor staging utilizes TNM system.
• Factors associated with prognosis include:
  • Positive surgical margins
  • Metastatic spread
  • Presence of sarcomatoid architecture
  • Tumor subtype, grade, and stage
    • Tumor stage most powerful prognostic indicator.
• Memorial Sloan-Kettering Cancer Center (MSKCC) Prognostic Factors Model was developed for patients with metastatic disease.
  • Low risk: No poor prognostic risk factors present.
  • Intermediate risk: One or two factors
  • High risk: ≥3 factors (Table 1)
• These criteria used by clinicians to determine optimal therapy.