Renal cell carcinoma (hypernephroma) is a relatively uncommon neoplasm, but its incidence has been steadily increasing over the past thirty years.  In the year 2006, 39,000 new cases and 13,000 deaths were recorded from this tumor. From 2000 to 2005 71 renal cancers were diagnosed at Rice Memorial Hospital with 23,301 total cancer cases diagnosed during that time period.  The breakdown by cancer stage and comparison with other community cancer centers is seen in Figure 1.

Although the cause of many cases is unknown, approximately half the cases seem related to obesity, smoking, and hypertension.  Some rare familial syndromes may include renal cancer.  Rarely long term renal dialysis and exposure to cadmium, lead, trichloroethylene, benzene or phenacetin-containing analgesics has been implicated.

More advanced tumor stage in the AJCC staging system is clearly related to prognosis
(Figure 2).  The staging system is summarized as follows:

Stage 1:            Tumor 7 centimeters or less in greatest dimension, limited to the kidney.

Stage 2:            Tumor greater than 7 centimeters but still confined to the kidney.

Stage 3:            Tumor Spread to perirenal fat or to a single lymph node, the renal vein, or the vena cava.

Stage 4:            Spread to more than one lymph node or to distant sites (most commonly lung, liver or bone).

Surgical excision is the preferred treatment for tumors in Stages 1-3 if resection is technically feasible, and even Stage 4 tumors are sometimes excised for palliation or to render other therapies more effective (Figure 3).

Both chemotherapy and immunotherapy have been disappointing in renal cell carcinoma with significant toxicities and infrequent durable remissions.

Over years of observation the hypervascularity of renal cancers has fascinated pathologists and frustrated surgeons performing biopsies and attempting resection of these lesions. More recent genetic studies and cellular biology advances show that most clear cell renal cancers (the most common histological type) show an aberrant Von Hippel-Lindau gene whose products mimic conditions of hypoxia and cause excess production of multiple vascular and other growth factors (Figure 4).  The knowledge that new blood vessel formation is needed for tumor growth and spread has led to trials of several new agents that block growth factors in multiple steps of their complicated synthesis pathways.

Sorafenib (Nexavaar), sunitinib (Sutent), and temsirolimus (Torisel) are three commercially available targeted therapies with documented success in treatment of advanced disease especially after palliative nephrectomy. Trials are ongoing in the early use of these agents after “curative” surgery for Stage 3 disease.

Hopefully these and future strategies will continually improve the outlook for patients with this uncommon but deadly neoplasm.

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