Kidney cancer

ALSO KNOWN AS: Renal cancer, renal-cell cancer, transitional-cell cancer, clear-cell renal cancer, papillary renal cancer, chromophil renal cancer, chromophobe renal cancer, renal oncocytoma, collecting-duct renal cancer, medullary renal cancer, sarcomatoid renal cancer, Wilms’ tumor

RELATED CONDITIONS: Kidney cysts

DEFINITION: The main types of kidney cancer are renal cell carcinoma (RCC), which arises from the nephrons, which are the filtering part of the kidney, and transitional-cell cancer, which arises from the renal pelvis, where the urine passes from the nephrons to the ureter and then to the bladder. It more closely resembles bladder cancer than RCC.

RCC accounts for 90 percent of kidney cancer cases, and it comprises several subtypes—clear cell, papillary, chromophobe, renal oncocytoma, collecting duct, medullary, sarcomatoid, Wilms’ tumor, and unclassified. Clear-cell cancer is the most common, representing 64 to 75 percent of all cases. Its name derives from the clear cytoplasm within its cells. A majority of clear-cell renal cancer cases have the von Hippel–Lindau (VHL) genetic mutation.

The two papillary renal cancers, sometimes called chromophil renal cancer, are characterized by fingerlike projections and differentiated by the type of tumor cells. Type I is more common in Black Americans, often involving both kidneys. Type II is associated with hereditary leiomyomatosis and can be difficult to treat once it has metastasized (spread to other organs). It is the second most common RCC, representing 10 to 15 percent of cases.

About 5 percent of renal cell cancers are chromophobe. The cells of this type of cancer are similar to those in renal oncocytoma, but they are resistant to some stains used to analyze cancer cells. Chromophobe renal cancer is often related to Birt-Hogg-Dubé syndrome (BHDS). This dominant hereditary trait is marked by renal tumors, lung cysts, fibrofolliculomas (benign tumors of hair follicles), and spontaneous pneumothorax (collapse of the lung). It is the third most common type of kidney cancer.

Renal oncocytoma is a benign kidney tumor related to BHDS. This type of tumor does not metastasize but can grow quite large. Its cells are similar to those of chromophobe renal cancer.

Collecting-duct renal cancer is rare but aggressive. Often, it metastasizes before being discovered. Its name comes from the tumor cells that usually form a tube. Medullary renal cancer and sarcomatoid renal cancer are also quite rare and aggressive. Medullary renal cancer is related to the sickle-cell trait, while sarcomatoid renal cancer arises from the blood vessels of the kidney. Its name comes from its cells appearing like those of sarcoma (cancer of the soft tissues). Wilms’ tumor is found predominantly in infants and young children under the age of five. It is rare and spreads locally into the lymph nodes, renal vein, and vena cava. Wilms’ tumor is an embryonal adenomyosarcoma. Unclassified renal cell cancer has cells that do not appear like those of other types of kidney cancer.

Risk factors: The most common risk factor for kidney cancer is smoking cigarettes. Kidney cancer also appears to be more common in persons who are obese or who have high blood pressure. Three hereditary syndromes put a person at a higher risk of developing kidney cancer—VHL disease, hereditary leiomyomatosis, and BHDS. Spontaneous mutations may cause these syndromes. Occupations that expose a person to certain toxic chemicals or substances, such as petroleum-based products, asbestos, lead, or cadmium, increase the risk of developing kidney cancer. Also, persons who are on long-term dialysis therapy for kidney failure are at higher risk of developing kidney cancer.

Etiology and the disease process: Kidney cancer arises from a single cell that grows wildly. For renal cell cancer, this is a cell of the tubular epithelium of the nephron, the part of the kidney that filters waste products from the blood and produces urine to excrete these wastes. Transitional-cell renal cancer manifests in the renal pelvis, where urine is delivered by the nephrons. Renal cancer types vary in aggressiveness and how quickly they metastasize. Some will metastasize from a small tumor in the kidney, and other types do not metastasize until they have engulfed the kidney. Kidney cancer spreads through the lymph nodes and bloodstream. Common sites for metastases are the other kidney, lung, adrenal gland, bones, and liver.

Incidence: Kidney cancer accounts for 2.5 to 3 percent of cancer cases globally. It is twice as common in men as in women, and Black Americans and American Indians or Alaska Natives also have higher incidence rates. In a lifetime, men have a one in forty-three chance of developing kidney cancer, while one in seventy-three women are diagnosed. Most diagnoses are in individuals over sixty.

Symptoms: The symptoms of kidney cancer do not appear until the tumor is fairly large or has metastasized. They include blood in the urine (hematuria), abdominal mass, back or flank pain, weight loss, recurrent fever, and fatigue. Blood tests may demonstrate a high serum calcium and either anemia or high red blood cell counts. A urine analysis test shows microscopic hematuria invisible to the eye. Kidney cancer can also cause hypertension.

Screening and diagnosis: No routine screening is performed for kidney cancer. However, kidney cancer may be found incidentally on a chest, abdominal, or pelvic ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) performed for another reason.

Kidney cancer surgeries include total radical nephrectomy, laparoscopic radical nephrectomy, partial nephrectomy, radiofrequency ablation (destroying the tumor with high-energy radio waves), cryoablation (freezing), and arterial embolization (blocking the artery feeding the tumor with material). The original total radical nephrectomy procedure, in which an eighteen-inch incision is made from below the mediastinum (breastbone) to the middle of the back, is no longer the sole surgical option. Several laparoscopic radical nephrectomy procedures are available. These laparoscopic procedures require a 3- to 4-inch incision and 3.5-inch incisions. Recovery time for the patient is four weeks rather than the twelve weeks of recovery necessary for the original procedure.

Kidney cancer is usually staged with a combination of the American Joint Committee on Cancer (AJCC) TNM staging system and a numeric grouping. “T” refers to the size of the tumor, “N” refers to lymph node involvement, and “M” refers to whether there are metastases. The stages are as follows:

• Stage I, T1a-T1b, N0, M0: The tumor is less than 7 centimeters (cm) with no lymph node involvement and no metastases.
• Stage II, T2, N0, M0: The tumor is greater than 7 cm with no spread outside the kidney.
• Stage III, T1a-T3b, N1, M0 or T3a-3c, N0, M0: The tumor has spread to a single lymph node but not metastasized, or has spread to adjacent tissue or structures, such as the adrenal glands, to fatty tissue around the kidney, or into the vena cava.
• Stage IV, T4, N0-N1, M0; any T, N2, M0; or any T, any N, M1: The tumor extends beyond the kidney locally and has spread into the lymph system. It is present in more than one lymph node. There may also be metastases to other organs.

Treatment and therapy: For many years, the only treatment for kidney cancer was to remove the affected kidney (nephrectomy) surgically. This was done unless the cancer was so far advanced that there was little hope for the patient. Kidney cancer did not respond well to either radiation therapy or chemotherapy. Consequently, these treatments were used only to treat metastatic kidney cancer, to relieve the symptoms, and to prolong the patient’s life.

Kidney cancer surgeries include total radical nephrectomy, laparoscopic radical nephrectomy, partial nephrectomy, radiofrequency ablation (destroying the tumor with high-energy radio waves), cryoablation (freezing), and arterial embolization (blocking the artery feeding the cancer with material). The original total radical nephrectomy procedure, in which an eighteen-inch incision is made from below the mediastinum (breast bone) to the middle of the back, is no longer the sole surgical option. Several laparoscopic radical nephrectomy procedures are available. These laparoscopic procedures require a 3- to 4-inch incision and 3.5-inch incisions. Recovery time for the patient is four weeks rather than the twelve weeks needed for the original method.

Radiation therapies to treat kidney cancer include stereotactic body radiotherapy (SBRT), external beam therapy (EBRT), and stereotactic radiotherapy. Advances in the development of chemotherapy drugs have benefited the treatment of kidney cancer. The focus of chemotherapy treatment for kidney cancer is to prolong the life of the patient. As a result, chemotherapy is reserved for treating advanced renal cancers with metastases. Kidney cancer may be treated with angiogenesis inhibitors (drugs that inhibit the growth of blood vessels feeding the tumors), such as sorafenib tosylate (Nexavar) and sunitinib malate (Sutent).

Other drugs include bevacizumab (Avastin), interleukin-2, and interferon. Bevacizumab is a monoclonal antibody that interferes with the growth and development of new blood vessels within a tumor. Interleukin-2 and interferon are biological therapies because the body normally produces them in small amounts. Their role in kidney cancer treatment is to stimulate the body’s normal immune defenses. Like other chemotherapy drugs, these drugs have many severe side effects.

The Food and Drug Administration (FDA) has approved several kidney cancer treatments. Temsirolimus (Torisel) is an enzyme inhibitor that interferes with cell growth, development, and survival. Pazopanib hydrochloride (Votrient), everolimus (Afinitor), and axitinib (Inlyta) also treat kidney cancer. Pazopanib hydrochloride and axitinib are tyrosine kinase inhibitors, and everolimus is a mammalian target of rapamycin (mTOR) inhibitors.

Prognosis, prevention, and outcomes: With kidney cancer, the prognosis depends on the stage of the cancer at diagnosis. In stages I and II, surgical intervention is likely to remove the cancer, and five-year survival rates are approximately 93 percent and 73 percent, respectively. In stages III and IV, the prognosis is guarded and depends on the patient’s response to treatments, particularly drug therapy. Survival rates are approximately 53 percent in stage III and 13 percent in stage IV. Treatment in these stages attempts to extend the patient’s life and provide a reasonable quality of life.

It is impossible to prevent kidney cancer, but avoiding cigarettes decreases the likelihood of developing kidney cancer. Other lifestyle choices, such as occupation, might also decrease the likelihood of developing kidney cancer, but many of the substances thought to cause kidney cancer are fairly pervasive in the environment. Some kidney cancers develop in people with no apparent risk factors for the disease.

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