Kidney Cancer OVERVIEW

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1 Kidney Cancer OVERVIEW Kidney cancer is the third most common genitourinary cancer in adults. There are approximately 54,000 new cancer cases each year in the United States, and the incidence of kidney cancer appears to be on the rise. Kidney cancer tends to occur most commonly in individuals over the age of 50 and is more common in men than in women. Most kidney cancers occur spontaneously, although some are associated with hereditary conditions, including von Hippel-Lindau disease and hereditary papillary renal cell carcinoma. Potential risk factors include cigarette smoking, obesity and high blood pressure. Although most growths that arise in the kidneys are cancers, about 30% of small kidney masses are benign. The most common types of benign kidney tumors are oncocytoma and angiomyolipoma. Renal cell carcinoma (RCC) is the most common type of kidney cancer. There are several sub-types of renal cell carcinoma. Clear cell (conventional) renal cell carcinoma is the most common sub-type and represents greater than 80% of renal cell carcinomas. Other sub-types include: Papillary renal cell carcinoma Chromophobe renal cell carcinoma Collecting duct renal cell carcinoma Medullary renal cell carcinoma Papillary and chromophobe variants of renal cell carcinoma may be less aggressive than clear cell renal cell carcinoma. Collecting duct and medullary sub-types are very aggressive cancers characterized by relatively poor outcomes. Local kidney cancer Approximately 60% of kidney cancers are diagnosed at a localized stage (cancer confined to kidney without evidence of spread). Localized cancers may be detected incidentally without causing symptoms or may be associated with hematuria (blood in the urine), flank pain or abdominal discomfort. Surgery is the most effective treatment, although in some cases (very small tumors or in patients who are not suitable candidates for surgery) other ablative techniques are available. Following surgical treatment, approximately 20% to 30% of patients with localized kidney cancers develop a reoccurrence. The overall 5-year survival for patients with localized kidney cancer is approximately 90%. Advanced kidney cancer Approximately 40% of kidney cancers are diagnosed at an advanced stage characterized by involvement of surrounding structures, spread to lymph nodes or metastasis to more distant sites. These tumors tend to be larger, and are more commonly high-grade and carry a higher risk of recurrence following treatment.

2 Because chemotherapy and radiation are ineffective against kidney cancer, surgery still plays an important role in the management of advanced kidney cancer, and may even be recommended in the setting of metastatic disease. Common sites of metastatic spread include the lung, bone and brain. The overall 5-year survival for regionally advanced kidney cancer (spread to adjacent structures and lymph nodes) is approximately 60% but decreases to 10% for distant metastatic disease. Signs & Symptoms Hematuria Gross Microscopic Abdominal or flank symptoms Pain Fullness or palpable mass Constitutional symptoms Fatigue Weight loss Fevers Other Hypertension (high blood pressure) Hypercalcemia (high calcium level in blood) Erythrocytosis (high blood counts) Liver dysfunction (elevation in liver enzymes) For many people, kidney cancer does not cause symptoms but is found incidentally on x-ray tests. In cases in which symptoms are present, the most common symptoms include hematuria (blood in the urine), abdominal discomfort or flank pain. Diagnosis Physical examination Abdominal CT scan Chest x-ray or CT scan Abdominal MRI (if indicated) Bone scan (if indicated) Head CT scan or MRI (if indicated) After taking a detailed medical history and performing a physical examination, the physician will order (or review previously performed) radiographic imaging. Most commonly, an abdominal CT scan with intravenous contrast is used to diagnose and stage kidney cancer. In cases in which contrast cannot be given because of allergy or renal dysfunction, a non-contrast CT scan or MRI can be performed. The appearance

3 of the kidney on radiographic imaging helps differentiate benign lesions from kidney cancer, provides important staging information, and helps determine the best treatment approach. Staging for kidney cancer Clinical staging is performed with Physical Examination, Abdominal CT scan, and Chest X-Ray. In cases of advanced or high-risk disease, additional testing such as MRI and Bone Scan may be necessary. The prognosis of kidney cancer is directly linked to the stage of disease. Staging is a process that demonstrates how far the cancer has spread. Both the treatment and prognosis (or outlook) for kidney cancer depend significantly on the stage of disease. T0 T1 T1a T1b T2 T3 T3a T3b T3c T4 N0 N1 N2 M0 M1 TNM SYSTEM Status No evidence of primary kidney tumor Tumor 7 cm or less limited to the kidney Tumor > 4 cm limited to the kidney Tumor >= 4 cm but <=7 cm limited to the kidney Tumor more than 7 cm limited to the kidney Tumor extends into major veins or invades perinephric tissue Tumor invades adrenal gland or perinephric tissue Tumor extends into renal vein or infra-diaphragmatic vena cava Tumor extends into supra-diaphragmatic vena cava Tumor invades beyond Gerota s fascia No regional lymph node metastasis Metastasis in a single regional lymph node Metastasis in multiple regional lymph nodes No distant metastases Distant metastasis Treatment Most kidney cancers are localized and can be managed with surgery. Treatment for localized kidney cancer include: Partial nephrectomy Radical nephrectomy Ablative therapy (radiofrequency ablation or cryosurgery) Active Surveillance (observation) Partial nephrectomy or removal of the tumor without removal of the entire kidney is often recommended in cases of smaller kidney tumors, in patients with a single kidney

4 or tumors in both kidneys, or in settings of impaired renal function. A partial nephrectomy may also be recommended in patients with Diabetes or Hypertension to preserve as much renal function as possible, even if the opposite kidney is normal. Currently, partial nephrectomy is most commonly used in tumors measuring 4 cm, although other factors impact whether or not a partial nephrectomy is possible or necessary. Partial nephrectomy can be performed either laparoscopically or with open surgery. In general, laparoscopic surgery is indicated for exophytic (the lesion protrudes from the kidney s surface) tumors. Open surgery, however, may be indicated in more complex cases (larger tumors, centrally located tumors or solitary kidneys). Laparoscopic and open partial nephrectomy are as effective as total or radical nephrectomy of early stage (stage T1) kidney cancer. Radical nephrectomy consists of removal of the entire kidney with the surrounding tissue and is most often used in cases in which a partial nephrectomy is not feasible because of tumor size or location. Radical nephrectomy is also the standard treatment for large tumors. For advanced stage kidney cancer, lymph node dissection, removal of other affected organs or structures, or tumor thrombectomy (removal of tumor thrombus from the vena cava) may be performed in conjunction with radical nephrectomy. Total nephrectomy may also be recommended in the setting of metastatic disease. Ablative therapies use radiofrequency energy and extremely low temperatures (cryoablation) to cause tissue destruction. Currently, the use of ablative therapies is limited to tumors >= 3 cm, peripherally located tumors because of limitations in the spread of the ablative effect. In addition, the effectiveness of ablative therapy compared to extirpative surgical therapy (partial and radical nephrectomy) is still under investigation. As a result, ablative therapy is most commonly used in older or medically unhealthy patients for whom the risk of surgical is too great. Active surveillance of small, early-stage, low-risk kidney cancers may be an option for those not interested in (or candidates for) surgery or ablative therapy, and consists of periodic re-imaging to determine the rate of tumor growth. In general, active surveillance may be appropriate in older individuals with small (>= 3 cm) kidney tumors for whom the risk of surgery is too great. Detection of uncharacteristic growth may prompt a decision regarding initiation of active treatment. Regionally advanced and metastatic kidney cancer presents a management challenge because renal cell carcinoma is not responsive to radiation therapy or traditional chemotherapy. Thus, surgery may still play a role, particularly in younger patients with adequate performance status. In cases of regional lymph node metastases or solitary distant metastases, such as a single lung nodule, radical nephrectomy combined with surgical removal of the metastases is often recommended as a standard treatment approach. Newer targeted agents known as tyrosine kinase inhibitors are being used to fight high-risk and metastatic kidney cancer. These agents act by targeting key regulatory pathways in cancer cells needs for cell survival. Tyrosine kinase inhibitors are being used in recurrent and metastatic disease, and are now being tested as an

5 adjunct to surgery in high-risk localized disease to decrease the chances of recurrence. Specifically, tyrosine kinase inhibitors when used in metastatic disease have yielded partial response in up to 15-25% of patients.