Renal Cell Carcinoma for USMLE Step 3
Start your One-Week Free Trial
Already subscribed? Log in »
Renal Cell Carcinoma for the USMLE Step 3
- Definition:
- Renal cell carcinoma (RCC) is the most common primary malignancy of the kidney, originating from the renal tubular epithelium. RCC accounts for approximately 85% of all kidney cancers, with clear cell carcinoma being the most common subtype.
- Epidemiology:
- RCC predominantly affects individuals aged 60-70 years and is more common in men. Key risk factors include:
- Smoking: Major modifiable risk factor.
- Obesity: Linked to an increased risk of RCC, particularly in women.
- Hypertension: Chronic hypertension, whether treated or untreated, is associated with RCC.
- Genetic Syndromes:
- Von Hippel-Lindau (VHL) disease: Associated with clear cell RCC due to mutations in the VHL gene.
- Chronic Kidney Disease: Patients on long-term dialysis are at higher risk due to acquired renal cystic disease.
- Pathophysiology:
- RCC originates from the proximal tubular epithelium and has several subtypes:
- Clear Cell RCC: The most common subtype, accounting for 75-85% of cases. These tumors often contain lipid and glycogen deposits, giving the cells a clear appearance.
- Papillary RCC: Makes up 10-15% of cases and has two subtypes (type 1 and type 2).
- Chromophobe RCC: A rarer subtype, associated with a better prognosis.
- RCC can invade local structures such as the renal vein and inferior vena cava (IVC) and commonly metastasizes to the lungs, bones, and liver.
- Clinical Presentation:
- RCC is often asymptomatic in its early stages and discovered incidentally. The classic triad of symptoms includes:
- Hematuria: The most common presenting symptom, either gross or microscopic.
- Flank Pain: Results from tumor growth, causing stretching of the renal capsule.
- Palpable Mass: Typically seen in advanced disease.
- Paraneoplastic Syndromes:
- Common in RCC and include:
- Hypercalcemia: Due to tumor production of parathyroid hormone-related peptide (PTHrP).
- Polycythemia: From erythropoietin production by the tumor.
- Hypertension: Linked to renin production by the tumor.
- Diagnosis:
- Imaging:
- CT Scan: The gold standard for diagnosing RCC. It provides detailed information about tumor size, local invasion, and distant metastasis.
- MRI: Used when there is concern about venous involvement (e.g., tumor thrombus in the IVC) or in patients where radiation is contraindicated.
- Urinalysis: Detects hematuria, though it is nonspecific for RCC.
- Biopsy: Not typically required if imaging findings are classic for RCC, but it may be necessary for indeterminate masses.
- Staging:
- RCC is staged using the TNM system:
- Stage I: Tumor confined to the kidney, ≤7 cm.
- Stage II: Tumor >7 cm, still confined to the kidney.
- Stage III: Tumor invades major veins or perinephric tissues but has no distant metastasis.
- Stage IV: Tumor invades adjacent organs or distant metastases are present.
- Management:
- Surgical Treatment:
- Radical Nephrectomy: Involves removal of the kidney, adrenal gland, and surrounding fat and is the treatment of choice for localized RCC.
- Partial Nephrectomy: Preferred for small tumors (<4 cm) or when preservation of renal function is critical (e.g., in patients with a solitary kidney).
- Systemic Therapy:
- Targeted Therapy: Includes tyrosine kinase inhibitors (e.g., sunitinib, pazopanib) and mTOR inhibitors (e.g., everolimus). These therapies inhibit angiogenesis and tumor growth.
- Immune Checkpoint Inhibitors: Drugs like nivolumab (PD-1 inhibitor) are used in advanced or metastatic RCC.
- Ablative Therapies:
- Radiofrequency ablation (RFA) and cryoablation are options for patients who are poor surgical candidates or have small tumors.
- Prognosis:
- Prognosis depends on the stage at diagnosis. For localized RCC, the five-year survival rate exceeds 90%. However, for metastatic disease, the survival rate drops to around 10-20%.
Key Points
- RCC is the most common kidney cancer, with clear cell carcinoma being the predominant subtype.
- Risk factors include smoking, obesity, hypertension, and genetic conditions such as Von Hippel-Lindau disease.
- RCC often presents with hematuria, flank pain, and paraneoplastic syndromes like hypercalcemia and polycythemia.
- Diagnosis relies on imaging, particularly CT, with biopsy reserved for indeterminate cases.
- Treatment for localized disease involves surgical resection, while advanced disease requires systemic therapies like targeted agents and immune checkpoint inhibitors.
- Prognosis depends on disease stage, with early-stage RCC having favorable outcomes.