Approximately 62,700 new cases of renal tumors will be diagnosed in the United States in 2016, with an estimated 14.240 deaths from the disease. There has been a steady increase in the incidence of renal cell carcinoma that is not explained by the increased use of diagnostic imaging procedures. Mortality rates have also shown a steady increase over the past 2 decades.
Gender and age
This malignancy is twice as common in men as in women. Most cases of renal cell carcinoma are diagnosed in the fourth to sixth decades of life, but the disease has been reported in all age groups.
Renal cell carcinoma is more common in persons of northern European ancestry than in those of African or Asian descent.
Renal cell carcinoma occurs most commonly as a sporadic form and rarely (2%) as a familial form. The exact etiology of sporadic renal cell carcinoma has not been determined. However, smoking, obesity, and renal dialysis have been associated with an increased incidence of the disease.
von Hippel-Lindau (VHL) disease. VHL disease, an autosomal-dominant disease, is associated with retinal angiomas, central nervous system hemangioblastomas, and renal cell carcinoma.
Chromosomal abnormalities. Deletions of the short arm of chromosome 3 (3p) occur commonly in renal cell carcinoma associated with VHL disease. In the rare familial forms of renal cell carcinoma, translocations affecting chromosome 3p can be present. Sporadic renal cell carcinoma of the clear cell is also associated with VHL-gene silencing.
Two studies from large patient databases have reported a higher-than-expected incidence of both renal cell cancer and lymphoma. No explanation for this association has been found.
Renal cell carcinoma has been associated with a wide array of signs and symptoms. The classic triad of hematuria, flank mass, and flank pain occurs in only 10% of patients and is usually associated with a poor prognosis. With the routine use of abdominal imaging for various diagnostic reasons, renal cell carcinoma is being diagnosed more frequently as an incidental finding.
Today, most patients presenting with a renal cell carcinoma are asymptomatic at time of diagnosis and are detected incidentally in the evaluation or surveillance for other unrelated medical conditions.
Relatively infrequently, patients can present with gross or microscopic hematuria, particularly if a large renal mass extends into the renal collecting system or if a renal vein/inferior vena cava tumor thrombus is present. For central renal tumors, the presence of a transitional cell carcinoma (rather than a renal cell carcinoma) should be considered and ruled out.
Other common signs/symptoms
Other commonly associated signs and symptoms of renal cell carcinoma include normocytic/normochromic anemia, fever, and weight loss.
Less common signs/symptoms
Less frequently occurring, but often described, signs and symptoms include polycythemia, hepatic dysfunction not associated with hepatic metastasis (termed “Stauffer syndrome”), and hypercalcemia. Although not a common finding at the time of diagnosis of renal cell carcinoma, hypercalcemia ultimately occurs in up to 25% of patients with metastatic disease.
Pre- and post-contrast–enhanced CT scanning
This technique has virtually replaced excretory urography and renal ultrasonography in the evaluation of suspected renal cell carcinoma. In most cases, CT imaging can differentiate cystic from solid masses and also supplies information about lymph nodes and renal vein/inferior vena cava (IVC) involvement.
Ultrasonography is useful in evaluating questionable cystic renal lesions if CT imaging is inconclusive.
Venography and MRI
When IVC involvement by tumor is suspected, either IVC venography or MRI is needed to evaluate its extent. MRI is currently the preferred imaging technique for assessing IVC involvement at most centers. Transesophageal echocardiography is occasionally obtained preoperatively or intraoperatively to determine the proximal extent of the IVC thrombus, particularly in lesions suspected to be above the diaphragm.
Renal arteriography is not commonly used in the evaluation of suspected renal cell carcinoma. In patients with small, indeterminate lesions, arteriography may be helpful. It can also be used by the surgeon as part of the preoperative evaluation and management of a large renal neoplasm.
Evaluation of extra-abdominal disease sites
This includes a chest x-ray film or CT imaging of the chest. A bone scan is required if a patient has symptoms suggestive of bone metastasis and/or an elevated alkaline phosphatase level.
Brain CT or MRI
A CT or MRI scan of the brain is indicated if neurologic signs or symptoms occur, or if it is needed for staging before systemic therapy is given.
Renal cell carcinoma arises from the proximal renal tubular epithelium. Histologically, renal cell carcinoma can be of various cellular types: clear cell (70% to 80%), papillary (10% to 15%), and chromophobe (5%). Oncocytoma is a benign renal tumor. Approximately 10% to 20% of renal cell carcinomas have sarcomatoid features (spindled cells that can occur in any subtype), which is a more aggressive malignancy with a worse prognosis.
The preferred staging system for renal cell carcinoma is the TNM classification (Table 3).
The natural history of renal cell carcinoma is highly variable. However, approximately 30% of patients present with metastatic disease at diagnosis, and one-third of the remainder will develop metastasis during follow-up.
Five-year survival rates after nephrectomy for tumors confined to the renal parenchyma (T1/2) are greater than 80%. Renal vein involvement without nodal involvement does not affect survival. Lymph node involvement and/or extracapsular spread is associated with a 5-year survival of 10% to 25%. Patients with metastatic disease have a median survival of 2 years.
Several prognostic schemes have been developed for both localized and metastatic renal cell carcinomas. In general, factors such as tumor stage and grade, performance status, hemoglobin value, calcium and lactate dehydrogenase levels, and time interval to development of metastatic disease are important.