Kidney cancer
Template:Short description Template:Cs1 config Template:Infobox medical condition (new)
Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney.<ref name=SEER2019/> Symptoms may include blood in the urine, a lump in the abdomen, or back pain.<ref name=NCI2019RCC>Template:Cite web</ref><ref name=NCI2019TCC>Template:Cite web</ref><ref name=NCI2019Wl>Template:Cite web</ref> Fever, weight loss, and tiredness may also occur.<ref name=NCI2019RCC/><ref name=NCI2019TCC/><ref name=NCI2019Wl/> Complications can include spread to the lungs or brain.<ref>Template:Cite book</ref>
The main types of kidney cancer are renal cell cancer (RCC), transitional cell cancer (TCC), and Wilms' tumor.<ref name=NCI2019Over>Template:Cite web</ref> RCC makes up approximately 80% of kidney cancers, and TCC accounts for most of the rest.<ref name="rccvsucc">Template:Cite journal</ref> Risk factors for RCC and TCC include smoking, certain pain medications, previous bladder cancer, being overweight, high blood pressure, certain chemicals, and a family history.<ref name=NCI2019RCC/><ref name=NCI2019TCC/> Risk factors for Wilms' tumor include a family history and certain genetic disorders such as WAGR syndrome.<ref name=NCI2019Wl/> Diagnosis may be suspected based on symptoms, urine testing, and medical imaging.<ref name=NCI2019RCC/><ref name=NCI2019TCC/><ref name=NCI2019Wl/> It is confirmed by tissue biopsy.<ref name=NCI2019RCC/><ref name=NCI2019TCC/><ref name=NCI2019Wl/>
Treatment may include surgery, radiation therapy, chemotherapy, immunotherapy, and targeted therapy.<ref name=NCI2019RCC/><ref name=NCI2019TCC/><ref name=NCI2019Wl/> Kidney cancer newly affected about 403,300 people and resulted in 175,000 deaths globally in 2018.<ref name=IARC2018>Template:Cite web</ref> Onset is usually after the age of 45.<ref name=SEER2019/> The overall five-year survival rate is 75% in the United States, 71% in Canada, 70% in China, and 60% in Europe.<ref name=SEER2019>Template:Cite web</ref><ref>Template:Cite web</ref><ref>Template:Cite web</ref><ref>Template:Cite journal</ref> For cancers that are confined to the kidney, the five-year survival rate is 93%, if it has spread to the surrounding lymph nodes it is 70%, and if it has spread widely, it is 12%.<ref name=SEER2019/> Kidney cancer has been identified as the 13th most common form of cancer,<ref name=":05">Template:Cite journal</ref> and is responsible for 2% of the world's cancer cases and deaths.<ref>Template:Cite journal</ref> The incidence of kidney cancer has continued to increase since 1930. Renal cancer is more commonly found in populations of urban areas than rural areas.<ref name=":14">Template:Cite journal</ref>
Signs and symptoms
Early on, kidney masses do not typically cause any symptoms and are undetectable on physical examination.<ref name=":07">Template:Cite book</ref> As kidney cancer becomes more advanced it classically results in blood in the urine, flank or back pain, and a mass.<ref name=":07"/> Other symptoms that are consistent with advanced disease include weight loss, fever, night sweats, palpable swollen lymph nodes in the neck, non-reducing varicocele, bone pain, continuous cough, and bilateral lower leg swelling.<ref name=":07"/><ref>Template:Cite journal</ref><ref>Template:Cite web</ref>
The classic triad of visible blood in the urine (hematuria), flank pain and palpable abdominal mass occurs in less than 15% of the cases. RCC may present with signs and symptoms caused by the substances the cancer cells produce (i.e. paraneoplastic syndromes).Template:Citation needed
Paraneoplastic syndromes caused by kidney cancer can be broadly classified as endocrine and non-endocrine. Endocrine dysfunctions include increase in blood calcium levels (hypercalcemia), high blood pressure (hypertension), increased red bloods (polycythemia), liver dysfunction, milky nipple discharge unrelated normal breast-feeding (galactorrhea), and Cushing's syndrome. Non-endocrine dysfunctions include deposition of protein in tissue (amyloidosis), decrease in hemoglobin or red blood cells (anemia), disorders of nerves, muscles (neuromyopathies), blood vessels (vasculopathy) and blood clotting mechanisms (coagulopathy).<ref>Template:Cite journal</ref>
Causes
Factors that increase the risk of kidney cancer include smoking, high blood pressure, obesity, faulty genes, a family history of kidney cancer in the first relatives,<ref>Template:Cite journal</ref> having kidney disease that needs dialysis, being infected with hepatitis C, and previous treatment for testicular cancer or cervical cancer.<ref>Template:Cite journal</ref><ref name=":1">Template:Cite web</ref>
There are also other possible risk factors such as kidney stones that are being investigated.<ref>Template:Cite journal</ref><ref>Template:Cite web</ref>
About 25–30% of kidney cancer is attributed to smoking.<ref name=":1" /> Smokers have a 1.3 times higher risk of developing kidney cancer compared to non-smokers. Moreover, there is a dose-dependent increased risk of cancer development. Men who smoke more than 20 cigarettes per day have twice the risk. Likewise, women who smoke more than 20 cigarettes per day have 1.5 times the risk of non-smokers. After 10 years of smoking cessation, a substantial reduction is seen in the risk of developing kidney cancer.<ref>Template:Cite journal</ref>
Diagnosis
Due to the increase in ultrasound and CT imaging for nonspecific abdominal complaints, kidney masses are frequently incidentally diagnosed on medical imaging.<ref name=":07" /><ref>Template:Cite journal</ref><ref name=":23">Template:Cite journal</ref> More than 60% of renal cell carcinoma (the most common type of kidney cancer), are diagnosed incidentally by abdominal imaging for nonspecific abdominal complaints.<ref name=":07" /><ref>Template:Cite journal</ref>
Kidney masses can be classified by the nature of the cells in the growth, or by its appearance on radiography.<ref name=":07"/> The term cancer refers to a malignant tumor, which is an uncontrolled growth of abnormal cells.<ref>Template:Cite web</ref> However, kidney masses can be due to growth of normal tissue (benign), inflammatory (a reaction of the immune system), or vascular (cells of the blood vessels).Template:Citation needed
Medical imaging
Since there is a large differential diagnosis for a kidney tumor, the first step is to characterize the mass with medical imaging to assess its likelihood of being benign or malignant. Ultrasonography is sometimes used to evaluate a suspected kidney mass, as it can characterize cystic and solid kidney masses without radiation exposure and at relatively low cost.<ref name=":07" /> Radiologically tumors are grouped based on appearance into simple cystic, complex cystic, or solid.<ref name=":07" /> The most important differentiating feature of a cancerous and non-cancerous tumor on imaging is enhancement.<ref>Template:Cite journal</ref><ref>Template:Cite web</ref> Simple cysts, which are defined by strict criteria<ref>Template:Cite journal</ref> are safe to be monitored if the person does not have any symptoms.<ref name=":07" /> However, all masses that are not clearly simple cysts should be further evaluated and confirmed by alternate imaging techniques.<ref name=":15">Template:Cite web</ref><ref name=":07" />
Computed tomography (CT) of the abdomen administered with and without IV contrast is the ideal imaging to diagnose and determine the stage of kidney cancer.<ref name=":2">Template:Cite journal</ref><ref name=":15" /><ref name=":07" /> There is tentative evidence that iodinated contrast agents may cause worsening of kidney function in people with chronic kidney disease (CKD) with a glomerular filtration rate (GFR) less than 45ml/min/1.73m2 and should therefore be given cautiously to such persons.<ref>Template:Cite book</ref>
Abdominal magnetic resonance imaging (MRI) is an alternative imaging method that can be used to characterize and stage a kidney mass.<ref name=":2"/><ref name=":15" /><ref name=":07" /> It may be suggested if contrast material cannot be given.<ref name=":2" /> MRI can also evaluate the inferior vena cava if the mass is suspected to extend outside the kidney.<ref name=":2" />
Since the lungs are the most common organ for kidney cancer to spread to, a chest X-ray or CT scan may be ordered based on the person's risk for metastatic disease.<ref name=":07" /><ref name=":15" />
Histopathologic classification
The most common type of kidney malignancy is renal cell carcinoma,<ref>Template:Cite web</ref> which is thought to originate from cells in the proximal convoluted tubule of the nephron.<ref name=":07"/><ref>Template:Cite web</ref> Another type of kidney cancer although less common, is transitional cell cancer (TCC) or urothelial carcinoma of the renal pelvis.<ref name=":5">Template:Cite web</ref> The renal pelvis is the part of the kidney that collects urine and drains it into a tube called the ureter.<ref name=":5" /> The cells that line the renal pelvis are called transitional cells, and are also sometimes called urothelial cells. The transitional/urothelial cells in the renal pelvis are the same type of cells that line the ureter and bladder. For this reason TCC of the renal pelvis is distinct from RCC and is thought to behave more like bladder cancer.<ref name=":5" /> Other rare types of kidney cancers that can arise from the urothelial cells of the renal pelvis are squamous cell carcinoma and adenocarcinoma.<ref name=":07"/>
Other causes of kidney cancer include the following:<ref name=":07"/>
- Sarcoma – for example leiomyosarcoma, liposarcoma, angiosarcoma, clear-cell sarcoma and rhabdomyosarcoma are types of sarcomas that have occurred in the kidney
- Metastatic tumor from distant organ
- Lymphoma
- Wilms tumor – an embryonic tumor that is the most common type of kidney cancer in children
- Carcinoid tumor of the renal pelvis<ref name="pmid18067641">Template:Cite journal</ref>
- Carcinosarcoma<ref name="pmid19016157">Template:Cite journal</ref>
- Inverted urothelial papilloma – was traditionally regarded as a benign growth. However, there may be an increased risk for recurrence and transformation to TCC.<ref>Template:Cite journal</ref>
In children, Wilms tumor is the most common type of kidney cancer.<ref name=":07"/> Mesoblastic nephroma, although rare, also typically presents in childhood.
Renal cell carcinoma has been further divided into sub-types based on histological features and genetic abnormalities. The 2004 WHO Classification of the Renal Tumors of the Adults describes these categories:<ref>Template:Cite journal</ref>
- Clear cell RCC
- Multilocular clear cell RCC
- Papillary RCC
- Chromophobe RCC
- Carcinoma of the collecting ducts of Bellini
- Renal medullary carcinoma
- Xp11 translocation carcinomas
- Carcinoma associated with neuroblastoma
- Mucinous tubular and spindle cell carcinoma
- Mixed epithelial stromal tumor<ref name="pmid16150156">Template:Cite journal</ref>
Tumors that are considered benign include angiomyolipoma, oncocytoma, reninoma (juxtaglomerular cell tumor), and renal adenoma.<ref name=":07"/>
Immunohistochemistry
| PAX8 | CD10 | CAIX | RCC | Melanocytic markers | Vimentin | CK7 | HMWCK | CD117 / KIT | AMACR | GATA3 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Clear cell RCC | + | + | + (box-like) | + | - | + | - | - | - | -/+ | - |
| Papillary RCC | + | + | +/- | + | - | + | + | - | - | + | - |
| Clear cell papillary RCC | + | - | + (cup-like) | +/- | - | + | + | +/- | - | - | +/- |
| Chromophobe RCC | + | -/+ | - | +/- | - | - | + | - | + | - | +/- |
| Oncocytoma | + | -/+ | - | - | - | - | Focal | - | + | -/+ | - |
| Angiomyolipoma | - | - | -/+ | - | + | -/+ | - | - | - | - | - |
| Collecting duct carcinoma | + | - | -/+ | - | - | + | +/- | + | - | - | - |
| Tubulocystic carcinoma | + | + | +/- | + | - | +/- | -/+ | - | - | +/- | - |
| Translocation RCC | + | +/- | -/+ | +/- | +/- | + | - | - | - | +/- | - |
| MTSCC | + | -/+ | -/+ | +/- | - | + | + | -/+ | - | +/- | - |
Legend:
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Laboratory studies
People with suspected kidney cancer should also have their kidney function evaluated to help determine treatment options. Blood tests to determine kidney function include a comprehensive metabolic panel (CMP) and a complete blood count (CBC).<ref name=":22">Template:Cite journal</ref><ref name=":15"/> In addition, these tests help understand the overall health of the person, which can be affected by metastatic disease (disease that is outside of the kidney). For example, liver or bone involvement could result in abnormal liver enzymes, electrolyte abnormalities, or anemia. A urine sample should also be collected for urinalysis.<ref name=":15"/><ref name=":07"/>
Biopsy
The utility of renal mass biopsy (RMB) lies in that it can confirm malignancy with reliability, can direct therapy based on diagnosis, and can provide drainage.<ref name=":15"/>
Once imaging has been completed, renal mass biopsy should be considered if there is a high likelihood that the mass is hematologic, metastatic, inflammatory, or infectious.<ref name=":15"/> These types of lesions would not be managed surgically, differing from cancer originating from the kidney. Cancer originating outside the kidney and lymphoma are managed systemically.<ref name=":07"/><ref name=":15"/>
RMB can accurately diagnose malignancy, however, it cannot reliably diagnose benign disease. In other words, if the biopsy shows cancer, there is a 99.8% chance that kidney cancer is present (Positive Predictive Value= 99.8%). A negative biopsy does not rule out a diagnosis of cancer.<ref>Template:Cite journal</ref>
Staging
Staging is the process that helps determine the extent and spread of the disease.<ref>Template:Cite web</ref> Renal cell carcinoma is the only type of kidney cancer that can be staged. The first step of staging follows the TNM staging system proposed by the Union International Contre le Cancer that is widely used among cancers in other organs.<ref name=":07"/> The TNM staging system classifies the primary tumor (T), lymph nodes (N) and distant metastasis (M) of the disease. The American Joint Committee on Cancer (AJCC) published a Cancer Staging Manual revision in 2010 that describes the values of TMN for renal cell carcinoma.<ref name=":3">Template:Cite book</ref><ref name=":07" />
Lymph node involvement is classified as either regional lymph node metastasis (N1), or no involvement (N0).<ref name=":3" /> Similarly, M1 describes distant metastasis, while M0 describes no distant metastasis.<ref name=":3" />
The primary tumor of renal cell carcinoma is categorized in the table below, as according to the AJCC 8th Edition Cancer Staging Manual:<ref>Template:Cite web Last Revised: February 1, 2020</ref><ref name="SwamiNussenzveig2019">Template:Cite journal</ref>
| Stage | TNM | Description |
|---|---|---|
| Tx, N0, M0 | Tumor cannot be assessed | |
| T0, N0, M0 | No evidence of primary tumor | |
| I | T1, N0, M0 | Tumor ≤7 cm; limited to kidney |
| T1a, N0, M0 | Tumor ≤4 cm; limited to kidney | |
| T1b, N0, M0 | Tumor 4-≤7 cm; limited to kidney | |
| II | T2, N0, M0 | Tumor >7 cm; limited to kidney |
| T2a, N0, M0 | Tumor 7-≤10 cm; limited to kidney | |
| T2b, N0, M0 | Tumor >10 cm; limited to kidney | |
| III | T3, N0, M0 | Tumor extends to major veins or perinephric tissue but not into ipsilateral adrenal gland nor beyond Gerota's fascia |
| T3a, N0, M0 | Tumor grossly extends into renal vein or its segmental branches, or tumor invades the pelvicalyceal system, or tumor invades perirenal and/or renal sinus fat but not beyond Gerota's fascia | |
| T3b, N0, M0 | Tumor grossly extends into vena cava below the diaphragm | |
| T3c, N0, M0 | Tumor grossly extends into vena cava above the diaphragm or invades the wall of the vena cava | |
| T1-T3, N1, M0 | The main tumor can be any size and may be outside the kidney, but it has not spread beyond Gerota's fascia. The cancer has spread to regional lymph nodes (N1) but has not spread to distant lymph nodes or other organs (M0). | |
| IV | T4, any N, M0 | Tumor invades beyond Gerota's fascia |
| Any T, any N, M1 | Tumor has spread to distant lymph nodes and/or other organs. |
The lungs are the most common site for metastasis,<ref name=":15"/> with other common sites including bone, brain, liver, adrenal gland and distant lymph nodes.<ref name=":22"/><ref name=":4">Template:Cite web Last Revised: May 16, 2016</ref><ref name=":3" />
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Stage 1 kidney cancer
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Stage 2 kidney cancer
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Stage 3 kidney cancer
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Stage 4 kidney cancer
Treatment
Treatment for kidney cancer depends on the type and stage of the disease. Surgery is the most common treatment as kidney cancer does not often respond to chemotherapy and radiotherapy. Surgical complexity can be estimated by the RENAL Nephrometry Scoring System. If the cancer has not spread it will usually be removed by surgery. In some cases this involves removing the whole kidney however most tumors are amenable to partial removal to eradicate the tumor and preserve the remaining normal portion of the kidney. Surgery is not always possible – for example, the patient may have other medical conditions that prevent it, or the cancer may have spread around the body and doctors may not be able to remove it.<ref>Template:Cite web</ref> If the cancer cannot be treated with surgery, other techniques such as freezing the tumour or treating it with high temperatures may be used. However, these are not yet used as standard treatments for kidney cancer.<ref>Template:Cite web</ref> Recently, evidence stemming from the KEYNOTE-564 study has shed light on the potential use of systemic therapy in the adjuvant setting, with promising results. Patients exhibiting specific clear cell RCC tumor characteristics and having undergone treatment with Pembrolizumab for 17 cycles (around 1 year) had significant improvement in disease-free survival. However, the study has yet to yield conclusive findings in relation to overall survival.<ref>Template:Cite journal</ref>
Other treatment options include biological therapies such as everolimus, torisel, nexavar, sutent, and axitinib, the use of immunotherapy including interferon and interleukin-2.<ref>Template:Cite web</ref><ref>Template:Cite web</ref><ref>Template:Cite web</ref> Immunotherapy is successful in 10 to 15% of people.<ref>Template:Cite web</ref> Sunitinib is the current standard of care in the adjuvant setting along with pazopanib; these treatments are often followed by everolimus, axitinib, and sorafenib. Immune checkpoint inhibitors are also in trials for kidney cancer, and some have gained approval for medical use.<ref name=":0">Template:Cite journal</ref>
In the second line setting, nivolumab demonstrated an overall survival advantage in advanced clear renal cell carcinoma over everolimus in 2015 and was approved by the FDA.<ref name=":0" /><ref>Template:Cite web</ref> Cabozantinib also demonstrated an overall survival benefit over everolimus and was approved by the FDA as a second-line treatment in 2016.<ref>Template:Cite journal</ref><ref>Template:Cite web</ref><ref>Template:Cite web</ref><ref name="Nat Med">Template:Cite journal</ref> Lenvatinib in combination with everolimus was approved in 2016 for patients who have had exactly one prior line of angiogenic therapy.<ref>Template:Cite web</ref>
In Wilms' tumor, chemotherapy, radiotherapy and surgery are the accepted treatments, depending on the stage of the disease when it is diagnosed.<ref name="wilms-tumour">Template:Cite web</ref>
Children
The majority of kidney cancers reported in children are Wilms' tumors. These tumors can begin to grow when a fetus is still developing in the uterus, and may not cause problems until the child is a few years old. Wilms' tumor is most common in children under the age of 5, but can rarely be diagnosed in older children or in adults. It is still not clear what causes most Wilms' tumors. The most common symptoms are swelling of the abdomen and blood in the urine.<ref name=wilms-tumour />
Epidemiology
Around 208,500 new cases of kidney cancer are diagnosed in the world each year, accounting for just under 2% of all cancers.<ref>Lindblad, P. and Adami H.O, Kidney Cancer, in Textbook of Cancer.</ref> The highest rates are recorded in North America and the lowest rates in Asia and Africa.<ref>GLOBOCAN 2002, Cancer Incidence, Mortality and Prevalence Worldwide 2002 estimates. 2006.</ref>
Lifestyle risk factors
Certain lifestyle factors have been associated with the development of renal cancer, although not all of them can be considered definitive causes. These include smoking, chemical carcinogens, radiation, viruses, diet and obesity, hypertension, diuretics,<ref name=":14"/> and alcohol consumption.<ref name=":05"/> Only a small percentage of kidney cancer cases have been linked to genetic factors.<ref name=":05"/> With obesity listed as one of the risk factors, daily physical activity and engaging in a healthy diet is proven to lower the rates of developing kidney cancer in the future.<ref name=":14"/>
Age
The incidence rate of renal cancer increases with the age of an individual, with 75 being the approximate age of the peak incidence rate, as of 2018.<ref name=":05"/> However, nearly one half of all cases are diagnosed before the age of 65.<ref name=":05"/> In both male and female children, renal tumors represent 2% to 6% of kidney cancer, with Wilms' tumor<ref name=":14"/> being the most common.
Sex
The incidence of kidney cancer is two times greater in men than in women, and this is thought to be due to biological differences. Mortality rates typically decrease more rapidly in women compared to men.<ref name=":05"/>
International variations
Incidence rates of kidney cancer can vary throughout the world. As of 2018, Czech Republic and Lithuania have the highest incidence rate of kidney cancer worldwide, with an age-standardized rate of 21.9/100,000 in males (Czech Republic) and 18.7/100,000 in males (Lithuania.) China, Thailand, and African countries (low-risk countries) have an incidence rate that is less than 2 in 100,000.<ref name=":05"/>
Since the early 2000s, Austria and Poland have been the only countries to report a decrease in kidney cancer rates.<ref name=":05"/>
Diagnosis access bias plays a large role in the epidemiology of kidney cancer. Differences in kidney cancer diagnosis across regions are likely due to differences in healthcare access, rather than a population's biological factors. Discrepancies in kidney cancer diagnosis has most likely led to the underrepresentation of mortality and incidence in low income countries.
Race
Race and ethnicity may be a factor in the distribution of kidney cancer around the United States. There are higher incidence rates in Black men and Hispanics, an average rate for American Indians, and low rates in Asians in the United States. Black people with kidney cancer have lower mortality rates than Caucasians in the United States.<ref name=":05"/>
Screening
Accessibility for cancer screening is not very common due to high expenses. Improving cancer registries can improve care to those who have kidney cancer as well as decreasing the incidence and death rates. Safe and dependable treatment is key with the screening and treatment, which is not always the case in developing nations.<ref>Template:Cite journal</ref>
United States
The United States' NIH estimates for 2013 around 64,770 new cases of kidney cancer and 13,570 deaths from the disease.<ref>Template:Cite web</ref>
The incidence of kidney cancer is also increasing in the United States. This is thought to be a real increase, not only due to changes in the way the disease is diagnosed.<ref>Template:Cite book</ref>
Europe
The most recent estimates of incidence of kidney cancer suggest that there are 63,300 new cases annually in the EU25. In Europe, kidney cancer accounts for nearly 3% of all cancer cases.<ref>Template:Cite journal</ref> Kidney cancer is the eighth most common cancer in the UK (around 10,100 people were diagnosed with the disease in 2011), and it is the fourteenth most common cause of cancer death (around 4,300 people died in 2012).<ref>Template:Cite web</ref>