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CLINICAL FEATURES AND NATURAL HISTORY
Renal cell carcinoma (RCC) is twice more common in men than in women; mean age at diagnosis is ~60 years. The most common symptoms of RCC are hematuria (usually intermittent, painless, sometimes in the form of cylindrical clots [casts of the ureteral lumen]), lumbar pain, weight loss, weakness, and periodic fever with night sweats. Signs and symptoms in advanced disease include tumor in the abdominal cavity, metastatic cervical and supraclavicular lymphadenopathy, edema of the lower extremities, varicocele (usually left sided; caused by compression or infiltration of venous vessels), and cachexia. The classic triad of hematuria, palpable mass, and lumbar pain is currently rare (<5% of patients). About 30% of patients have paraneoplastic syndromes.
1. Blood tests: Anemia (in up to 80% patients), rarely hypercalcemia or polycythemia (due to excessive erythropoietin production by cancer cells).
2. Urinalysis: Macroscopic or microscopic hematuria.
3. Imaging tests:
1) Ultrasonography: 40% to 60% of kidney tumors are detected incidentally during an examination performed for another reason.
2) Contrast-enhanced computed tomography (CT) of the abdominal cavity and pelvis is the basic modality for kidney tumor staging. It is used to determine the size of the tumor or identify RCC thrombus in the renal vein or inferior vena cava, lymph node enlargement, and liver metastases.
3) Renal arteriography visualizes the tumor vasculature, which is helpful while planning large tumor resection or embolization of the renal artery.
4) Magnetic resonance imaging (MRI) is usually performed if iodinated contrast agents are contraindicated and is particularly useful when testing for metastases to the adrenal gland.
5) Bone scintigraphy is performed when metastases are suspected.
6) Chest radiography and CT; CT of the brain: These are used to assess the extent of the disease (metastases).
4. Morphologic and histologic examination of the removed tumor and adjacent lymph nodes are necessary to establish prognosis and plan further treatment.
Any solid focal lesion in the kidney that cannot be clearly diagnosed as benign should be surgically removed (through nephrectomy or kidney-sparing surgery). If the clinical features indicate tumor with distant metastases, tissue samples from the metastatic lesion can be collected for histologic examination to confirm with very high probability that RCC is the source of the neoplastic spread. Staging is performed based on the tumor, node, metastasis (TNM) classification.
Simple and multiple cysts of the kidney, angiomyolipoma of the kidney, metastatic cancers (most often breast cancer, lung cancer, and lymphomas), xanthogranulomatous pyelonephritis.
Radical treatment is possible in patients with stage I, II, and III tumors (the cancer does not extend beyond Gerota fascia [renal fascia; fibrous connective tissue that encapsulates the kidneys and adrenal glands] and there are no metastases). Radical nephrectomy or minimally invasive laparoscopic nephrectomy is performed to remove the kidney together with the perirenal fat capsule, renal fascia, adrenal gland, and adjacent lymph nodes. In selected patients (tumor <4 cm located in the renal pole or peripherally or need to preserve the affected kidney), kidney-sparing surgery is performed (complete tumor removal with preserving the unaffected portion of the kidney).
1. Palliative surgery is considered when complete tumor removal is not possible and the large tumor or massive lymph node metastases are causing bleeding or complications from other organs.
2. Microwave or radiofrequency ablation is performed for kidney tumors sized <3 cm in patients with contraindications to surgery.
3. Embolization of the renal artery is performed as a preparatory procedure for nephrectomy or as a palliative procedure; the aim is to inhibit hematuria and reduce tumor mass and collateral circulation.
4. Systemic treatment: Traditional chemotherapy is ineffective in the vast majority of patients. New drugs (receptor tyrosine kinase inhibitors [cabozantinib, sunitinib, sorafenib, pazopanib and axitinib, lenvatinib, tivozanib], mTOR serine-threonine kinase inhibitors [temsirolimus and everolimus], anti–vascular endothelial growth factor [VEGF] monoclonal antibody [bevacizumab 1], anti–cytotoxic T-lymphocyte associated protein 4 [anti-CTLA-4] antibody [ipilimumab], programmed cell death protein 1 [PD-1] inhibitors [pembrolizumab, nivolumab]) improved prognosis in advanced RCC (prolonged median overall survival and progression-free survival). These drugs are used as monotherapy or in combination, depending on the histologic type of RCC and risk group.
