What is Renal Clear Cell Cancer?
Renal cell carcinoma (RCC), commonly known as kidney cancer, is one of the predominant types of kidney tumours. Clear cell carcinoma, making up 80 to 90 percent of all kidney cancer cases, is the most regularly occurring type. When we look at kidney cancer under the microscope, we can group them into three main types: clear cell, papillary, and chromophobe.
Clear cell and papillary types of cancer start from the cells in the initial part of our kidney tubes, whereas chromophobe types start from what we call ‘intercalated cells’. The likelihood of these types of cancer spreading to other parts of the body is different; clear cell carcinoma has a 15 percent chance, while it’s 3 percent for papillary and 4 percent for chromophobe types.
If we talk about cancer-specific 10-year survival, it’s 71 percent for clear cell cancer, 91 percent for papillary cancer, 88 percent for chromophobe cancer, and 33 percent for collecting duct cancers. As you might expect, catching the cancer at an early stage can significantly increase the chances of being cured. When it comes to dealing with advanced kidney cancer, the main goal is to improve the person’s quality of life.
It’s important to note that clear cell tumors typically spread through our body’s blood vessels, including the major ones like the renal veins and the inferior vena cava, affecting organs like lungs, bones, brain, liver, lymph nodes, liver, and adrenal glands. Sometimes, you may find that the cancer has caused lytic bony metastases, which can become hardened with treatment. Furthermore, irrespective of its size, clear cell carcinoma is known to potentially spread to other parts of the body.
What Causes Renal Clear Cell Cancer?
Obesity, high blood pressure, and smoking are the top changeable risk factors that can lead to kidney cancer. Also, a rise in Body Mass Index (BMI), central body fat, and an increase in body weight between the ages of 18 and 35 years have been found to increase the likelihood of developing kidney cancer in different groups of people.
Furthermore, chronic kidney disease, kidney transplants, dialysis, a type of kidney disease where cysts form in the kidney, having had kidney cancer before, and having diabetes have all been identified as possible risk factors that can increase the chances of kidney cancer.
The effects of moderate alcohol consumption, exercise, and the impact of individual’s financial standing on the likelihood of developing kidney cancer have received mixed results, with a general consensus that more research should be done on them.
Most kidney cancers are random, but a small percentage (2 to 3%) of cases are linked to changes in specific genes. These include the von Hippel Lindau gene, genes that help control how the cell’s machinery works (Polybromo 1, BRCA1, and SET D1), and genes that interfere with specific signaling paths within the cell (the PI3K/Akt/mTOR pathway). It is important to note that a deficiency in a gene called PTEN is often linked to a more aggressive type of kidney cancer.
While kidney tumors called angiomyolipomas (AML) are most commonly seen in people with a genetic disorder called tuberous sclerosis, clear cell tumors may occasionally occur. Clear cell tumors can also be found in a small group of individuals with Birt Hogg Dube syndrome, who generally develop hybrid-chromophobe tumors and oncocytomas.
Risk Factors and Frequency for Renal Clear Cell Cancer
Every year, about 295,000 cases of renal cell carcinoma (RCC) are diagnosed globally, with 134,000 fatalities recorded. In 2018, the United States had about 65,340 new cases and 14,970 deaths. The disease affects males twice as often as females. RCC is the twentieth leading cause of cancer-related death, based on the number of years of life lost. In contrast, it was in the nineteenth place in 2007.
The average age at which people are diagnosed is 64. If someone is diagnosed at a younger age, doctors may want to check if there’s a genetic syndrome that could be causing the disease. The incidence or number of new cases of RCC has been increasing due in part to rising obesity rates. However, the death rate has been declining, which could be due to improvements in treatment options.
Among European countries, the Czech Republic has the highest rate of RCC. RCC is responsible for 2.6% of all cancer-related deaths in men and 2.1% in women. According to the SEER data from 2012, the five-year survival rate for localized disease (when the cancer has not spread beyond the kidneys) is 91.7%. But if the cancer has spread to nearby regions or distant parts of the body, the five-year survival rates are 64.2% and 12.3% respectively.
Signs and Symptoms of Renal Clear Cell Cancer
Renal cell carcinoma, a type of kidney cancer, is often characterized by three key symptoms: flank pain, an abdominal mass, and blood in the urine (haematuria). However, due to advancements in medical technologies, many cases are now discovered incidentally, and only about 30% of cases are diagnosed based on these symptoms alone. Some people may experience other symptoms which can be caused by hormones or substances produced by the tumor.
People with renal cell carcinoma often feel acute or chronic flank pain. This is due to either a blockage in the urinary system, an invasion of nearby organs, or the presence of a mass in the rear of the body above the waist (retroperitoneum). While less common, visible blood in the urine due to the urinary tract and a palpable abdominal mass are also observed.
In some rare instances, there may be an isolated enlargement of veins in the scrotum (varicocele) due to blockage or clotting in the veins. Health issues that often occur together with kidney cancer include high blood pressure, anemia, and severe weight loss and muscle wasting (cachexia) associated with cancer.
Substances causing inflammation and fever (cytokines) may lead to harmful health effects such as anemia and muscle wasting. In rare cases, excessive proteins in the blood can cause a type of liver dysfunction called Stauffer syndrome, though this usually resolves after the kidney tumor is removed. High calcium levels in the blood may also occur due to effects on the bones and other parts of the body.
Production of erythropoietin, a hormone that promotes the formation of red blood cells, may increase in response to low oxygen levels (hypoxia), leading to too many red blood cells (polycythemia). In rare cases, kidney cancer can cause a range of other symptoms including low blood sugar, nerve issues (neuropathy), muscle issues (myopathy), blood clots, Cushing syndrome, digestive issues due to protein absorption, male breast enlargement (gynecomastia), decreased sexual desire, excessive hair growth (hirsutism), missed menstrual periods (amenorrhoea), muscle disease causing muscle inflammation and damage (necrotizing myopathy), and a type of bleeding disorder (immune thrombocytopenic purpura).
Even though physical check-ups play a limited role in diagnosing this condition, the presence of an abdominal mass, swelling in the lower extremities, and a newly developed varicocele should lead to further investigation for a mass in the area at the back of the abdomen.
Testing for Renal Clear Cell Cancer
If you’re experiencing symptoms of a kidney or retroperitoneal (behind the abdomen) mass, your doctor may use different ways to find out more about your condition, such as blood tests, imaging scans, and even a biopsy to determine the exact stage of the disease.
Firstly, blood tests would be conducted to measure various components of your blood, including creatinine (a waste product removed by kidneys), hemoglobin (protein that carries oxygen), different types of white blood cells, and platelets, among other things.
Imaging tests, such as ultrasonography, can help your doctor form an initial diagnosis of a kidney mass. These tests can determine the size and character of the mass, its impact on surrounding tissues, and if the tumor has spread. They can also check whether the large blood vessels in the area are affected, and whether there are any signs of the mass spreading in the back of your abdomen, all crucial if surgery is being considered.
Clear cell renal cell carcinoma (RCC), a common type of kidney cancer, typically shows certain distinct features in imaging scans, such as a tendency to grow outwards, variations within the tumor, and changes when a contrast dye is used.
Other imaging tests like computed tomography (CT scans) of the chest, abdomen, and pelvis, MRI of the brain, and bone scans may be needed to fully investigate whether the cancer has spread to other parts of the body. However, CT scans of the brain or bone scans are not routinely needed. In some cases, especially those who are allergic to the contrast dye used for CT scans, or who have kidney problems, a CT scan without contrast, along with an MRI of the abdomen, may be preferred.
The role of MRI techniques is also being explored for further characterization of the tumor. Clear cell tumors often show higher uptake of radioactive glucose in PET (Positron emission tomography) scans, but this use is limited due to normal excretion by the kidneys leading to inaccurate results. However, this technology has shown promise in situations where the disease has come back and in advanced disease staging.
A biopsy, where a small sample of the tumor is removed and examined under a microscope, is also useful. It’s especially helpful for tumors where radiology cannot give a clear diagnosis, in instances where the tumor is being closely monitored, and to determine which targeted therapy may be best for tumors that have spread. However, it can sometimes lead to complications such as infection, bleeding, or formation of abnormal connections between arteries and veins (arteriovenous fistula), and hence is performed judiciously.
Doctors are also researching “liquid biopsies,” where they analyze circulating tumor cells and DNA in the blood. Granular studies of tumor cells, proteins, and genetic material can help measure the tumor’s burden noninvasively and fairly accurately. This evolving technique may also help predict the response to certain therapies. Clear cell cancer is being studied for its unique features at the single-cell level through these methods.
Your healthcare team will decide the most effective combination of these tests based on your specific case to achieve an accurate diagnosis.
Treatment Options for Renal Clear Cell Cancer
sorry, Error during response generation.
What else can Renal Clear Cell Cancer be?
When doctors find a mass in a patient’s kidney, there are several conditions that it could potentially be. Here are some possibilities:
- Abscess (a confined pocket of pus)
- Metastasis from a cancer elsewhere in the body
- Metastatic melanoma (a type of skin cancer that has spread)
- Renal cyst (a fluid-filled sac in the kidney)
- Renal infarction (a type of stroke in the kidney)
- Sarcoma (a type of cancer)
- Renal AML (a benign kidney tumor)
- Renal oncocytoma (another benign kidney tumor)
- Lymphoma (a type of blood cancer)
- Other types of renal cell carcinoma (kidney cancer)
Mentioned here are three examples of possible diagnoses:
Renal Angiomyolipoma: This is the most common non-cancerous kidney tumor. It can be associated with certain diseases or it can develop on its own. It’s more common in middle-aged women. Most of the time, this tumor doesn’t cause any symptoms, but large tumors can cause bleeding. These tumors usually have fatty tissue inside them which is a clear indication of this condition. Some may not have this feature though, making diagnosis challenging.
Renal Oncocytoma: This is the second most common non-cancerous kidney tumor. It’s difficult to tell this tumor apart from kidney cancer just based on pictures from an imaging test, but there are certain features that could help doctors identify it.
Renal Lymphomas: These are unusual and can often look like kidney cancer. Certain features, such as a cystic component, vascular extension, or calcification, may suggest that the mass is kidney cancer rather than a lymphoma.
What to expect with Renal Clear Cell Cancer
There’s growing evidence that inflammation plays a key role in kidney cancer prognosis. Both local immune responses and body-wide inflammation seem to be heavily involved in the start and progression of cancer. Immune cells like neutrophils, lymphocytes, and monocytes have been found to aid in the entry of cancer cells into blood vessels. This aids angiogenesis (the formation of new blood vessels) and promotes spread of the cancer to other parts of the body, leading to poorer outcomes. Doctors can measure systemic inflammation through levels of C-reactive protein and ratios of different blood components like the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and other measurements like the prognostic nutritional index (PNI), systemic immune inflammation index (SIII) and systemic inflammation response index (SIRI). Studies point to poor outcomes if the NLR is equal to or more than 4.
Various blood and bodily measures may be used to identify the response to targeted therapy, including blood hemoglobin levels, absolute neutrophil count, platelet count, serum corrected calcium level and a person’s functional ability (Karnofsky performance status). The size and stage of the tumor and the extent of vascular invasion also factor into predicting survival. Certain substances in the body, such as proteins in the plasma, and specific mutations can guide personalized treatment strategies. Other factors indicating poorer prognosis might include failure to respond to radiotherapy, presence of cancer at multiple sites, thrombocytosis (high platelet count), and elevated alkaline phosphatase (an enzyme found in several tissues throughout the body). High serum interleukin 6 levels above 35 pg/ml and unfavorable scores on the modified Glasgow prognostic score also indicate poor survival chances.
Certain calculators or nomograms are used by doctors to decide the specific treatment plan. These include the UCLA Integrated Staging System and Stage, Size, Grade, Necrosis (SSGN) score. The Memorial Sloane-Kettering Cancer Center Score, takes into account factors like the patient’s performance status, history of kidney removal surgery, lactate dehydrogenase levels, hemoglobin level and serum calcium levels to predict survival in those with advanced disease who have underwent immunotherapy or chemotherapy.
In metastatic kidney cancer, the Motzer score system is used for prognostic evaluation. It considers laboratory parameters such as hemoglobin, total white blood cells, platelet counts, lactate dehydrogenase level, and corrected calcium levels. Survival times are estimated at about 43.2 months for persons with a favorable risk profile, whereas those with intermediate and unfavorable risk have a survival duration of about 22.5 and 7.8 months, respectively.
People with high blood pressure undergoing targeted therapy with multi-target tyrosine kinase inhibitors seem to have improved survival rates. As for the histopathological features, several characteristics like the type of tumor, presence of necrosis, presence of microscopic vascular invasion, the staging, and the status of non-cancerous kidney tissue are taken into account. Tumors with large size, presence of intralesional necrosis, renal vein thrombosis, retroperitoneal collateral vessels, and interruption of the tumor capsule tend to be of high grade and are usually associated with poor outcomes.
CT scans may also help by identifying the tumor’s microvascular density – a higher density is associated with better outcomes. There’s also been a shift towards studying genetic markers which may impact treatment in a more advanced stage of kidney cancer. Trials have shown that mutations in the BAP1 gene can impact progression-free survival.
The presence and density of lymphocytes in the tumor environment, as determined by PD-L1 expression, can also provide important prognostic information and might be used to assess responses to immune checkpoint inhibitor therapy. However, the expression of this marker may vary between the primary tumor and metastatic sites, which could limit its usefulness.
Possible Complications When Diagnosed with Renal Clear Cell Cancer
Complications after a Radical Nephrectomy
Frequent complications reported after performing radical nephrectomy can include extensive bleeding, infections in the wound, fluid-filled sac under the skin (seroma), opening of the wound, air in the chest cavity (pneumothorax), unfortunate spread of an infection (sepsis), delayed gastric emptying (ileus), heart failure, kidney issues, inflammation of the lining of the abdominal wall (peritonitis), and fluid collection near the liver.
- Severe bleeding
- Infections in the wound
- Fluid-filled sac under the skin
- Wound disruption
- Air in the chest cavity
- Spread of infection
- Delayed gastric emptying
- Heart failure
- Kidney complications
- Inflammation of the abdominal wall
- Fluid collection near the liver
Complications related to the Location of Metastasis
When cancer spreads to the bones, it can lead to bone-related issues such as easy fractures, high levels of calcium in the blood, or spinal cord compression. If the metastasis happens in the brain, it can cause changes in the functioning of the brain, signs of increased brain pressure like headaches, blurry vision, nausea and vomiting in the morning. A physical examination might show swelling of the optic disk (papilledema).
Distinct Side Effects of VEGF Targeted Therapy
In a study of over a thousand patients treated with drugs that block certain proteins (receptor tyrosine kinase inhibitors), the average time it took for high blood pressure to develop was 29 days from the start of therapy. Having preexisting high blood pressure, being overweight, and being over 60 years old were recognized as possible risk factors for developing hypertension.
Kidney Disease with RTK Therapy
Protein in the urine was found in about 18.7 percent of patients, while severe proteinuria was found in about 2.4 percent of patients, according to an analysis of 33 trials of patients with solid tumors treated with tyrosine kinase inhibitors (TKIs). Studying biopsy samples showed diseases of the glomeruli – tiny structures in the kidneys – such as minimal change disease and focal segmental glomerulosclerosis. The mechanism of these kidney diseases could be the uncontrolled activation of certain proteins, known as nephrin in the glomeruli.
Preventing Renal Clear Cell Cancer
If you notice any blood in your urine, feel a lump in your stomach, or experience pain on the side of your lower back, it’s important to talk to a doctor who specializes in the urinary system (a urologist). The healthcare team will ensure that you have all the necessary information about kidney cancer. You might also be directed to educational websites to help you better understand this type of cancer, its expected progress, and treatment options. Learning about kidney cancer can help in making choices that might reduce the chance of developing it. This is often taught by nurses who are specially trained in this area. For example, they might recommend that you quit smoking, as kidney cancer is known to be linked with tobacco use.
