Kidney Cancer

Definition

Kidney cancer tends to occur most commonly in individuals over the age of 40 and is more common in men than in women. It is the third most commonly occurring genitourinary cancer in adults, with approximately 54,000 new cancer cases each year in the United States.

Alternate names

Renal Cancer; Renal Cell Carcinoma

Causes, incidence and risk factors

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.

Kidney cancer tends to occur most commonly in individuals over the age of 40 and is more common in men than in women.

Types

Although most growths that arise in the kidneys are cancers, about 20 percent to 25 percent of kidney tumors are benign. The most common types of benign kidney tumors are oncocytoma and angiomyolipoma. Renal cell carcinoma, or RCC, is the most common type of kidney cancer. There are several subtypes of renal cell carcinoma. Clear cell (conventional) renal cell carcinoma is the most common subtype and represents greater than 80 percent of renal cell carcinomas.

Other subtypes 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 are typically less aggressive than clear cell renal cell carcinoma. Collecting duct and medullary subtypes are very aggressive cancers characterized by relatively poor outcomes.

Local Kidney Cancer

Approximately 60 percent 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. After surgical treatment, approximately 20 percent to 30 percent of patients with localized kidney cancers relapse (develop recurrent disease). The overall five-year survival for patients with localized kidney cancer is approximately 90 percent.

Advanced Kidney Cancer

Approximately 40 percent 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 after treatment. Because chemotherapy and radiation are ineffective against kidney cancer, surgery still holds 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 five-year survival for regionally advanced kidney cancer (spread to adjacent structures and lymph nodes) is approximately 60 percent but decreases to 10 percent for distant metastatic disease.

Signs and symptoms

Hematuria

  • Visible
  • Microscopic

Abdominal or Flank Symptoms

  • Pain
  • Fullness or palpable mass

Constitutional Symptoms

  • Fatigue
  • Weight loss
  • Fevers

Paraneoplastic Syndromes

  • 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 radiographic tests. In cases in which symptoms are present, the most common symptoms include hematuria (blood in the urine), abdominal discomfort or flank pain.

Tests

  • 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 (IV) 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 of the kidney on radiographic imaging helps differentiate benign lesions from kidney cancer, provides important staging information and helps determine the best treatment approach.

Clinical staging is determined through physical examination, abdominal CT scan and chest X-ray. In cases of advanced or high-risk disease, additional testing such as MRI and a 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.

Treatment

Most kidney cancers are localized and can be managed with surgery. Treatments for localized kidney cancer include:

Ablative Therapies

Ablative Therapies use radiofrequency energy and extremely low temperatures 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 surgery is too great.

Active Surveillance

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 reimaging 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.

Partial Nephrectomy

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 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 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

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 high-risk kidney cancers. 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 followed by systemic immunotherapy.

Systemic Immunotherapy

Systemic immunotherapy using interferon and interleukin-2 to augment the ability of the immune system to fight the cancer has been used in patients with metastatic disease with some effectiveness; approximately 15 percent of patients have a partial response, and between 3 percent and 5 percent have a complete response with regression of their cancer. Currently, 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 adjunct to surgery in high-risk localized disease to decrease the chances of recurrence.

Regionally advanced and metastatic kidney cancer presents several management challenges because renal cell carcinoma is not responsive to radiation therapy or traditional chemotherapy. As stated earlier, surgery may 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.