What is Renal Cancer? Symptoms, Cause, Diagnosis, and Treatments

 

Kidney cancer is the abnormal growth of kidney tissues. It results when healthy kidney cells grow in excess, forming a lump known as a tumour. Kidney cancer is a malignant tumour that can spread to other organs and cause complications. 

There are many types of renal cancer but renal cell cancer (RCC) is the most common type of cancer in adults. Other types include transitional cell cancer (TCC), Chromophobe renal cell carcinoma, papillary renal cell cancer (PRCC) and Wilms tumour.

Kidneys are bean-paired organs, each with the size of a fist. They are located in the abdomen on each side of the spine.  Nephrons are the structural unit of kidneys. The renal corpuscles and renal tubules make up the kidneys.

The tubules filter substances from the blood and return needed ones to it, while removing waste in the form of urine.

Like other organs, kidneys are made up of cellular tissues. Sometimes, cells start growing abnormally in the kidney tissues. The abnormal behaviour of cells results in DNA changes and forms tumours.

The formation of tumours also damages other organs of the body, such as bones, lungs, or the brain. Renal cell carcinoma originates in the renal tubule, more commonly in the proximal convoluted tubule.

The growth pattern of tumours may occur in one or both kidneys. It may be benign or malignant. The benign tumours are non-cancerous and do not spread to other parts of the body. Malignant tumours are cancerous and cause problems in other organs.

Renal cell carcinoma is a malignant type of cancer. The doctor recommends removing it immediately.

Renal cancer is more common in older people aged 65 to 74 years. Males are twice as likely to develop kidney cancer as compared to females, and most common in the Native American and Black populations.

The NIH reports that doctors diagnose about 500-600 children with Wilm’s tumour annually, a rare type of kidney cancer that is uncommon in children.

2. Types of Kidney Cancer

Here are some types of kidney cancer.

2.1 Renal Cell Carcinoma (RCC)

Renal cell carcinoma forms in the tiny tubes of the kidney and is the most common type of cancer. According to the American Cancer Society, about 9 out of 10 renal cancers are types of renal cell carcinoma (RCC).

It mostly forms a single tumour in a kidney, but a person may also have more than one tumour in one or both kidneys at a time. RCC has further subtypes, including.

2.1.1 Clear cell renal cell carcinoma (ccRCC): 

ccRCC is the most common subtype and makes up 80% (7 out of 10) of RCC cases. The tumor of ccRCC looks very pale or clear when viewed under a microscope. The cells of ccRCC rapidly multiplies to form more than one tumour. It mostly affects one kidney but can affect both kidneys too.

It affects twice as many males as compared to females of age 50-70 years. Children and young adults account for ccRCC in less than 6% of total cases.

2.1.2 Xp11 translocation 

Xp11 translocation is a type of renal cell carcinoma (RCC) that characterizes the chromosomal translocation of the TFE3 transcription gene factor. This subtype of RCC was first diagnosed in children. Xp11 translocation accounts for approximately 40% of RCC, with a range from 20% to 75% of paediatric RCC cases and 1-1.6% in adult cases of RCC.

2.1.3 Cystic-solid

This rare type of renal cell carcinoma mostly affects individuals with acquired cystic kidney disease who are undergoing dialysis. Doctors often detect it during routine imaging scans or screenings for kidney issues. Doctors recommend kidney biopsy to confirm the diagnosis of cystic-solid renal cell carcinoma.

2.1.4 Papillary RCC

Papillary RCC is a sub-type of renal cell carcinoma that accounts for 10-15% of all renal cancers. It forms finger-like projections (also known as papillae) of tumours formed usually in the kidney tubes.

Papillary RCC is further divided into two types, type 1 and type 2. Type 1 PRCC is more common and usually grows slowly, but type 2 PRCC is aggressive and grows more quickly. 

2.1.5 Chromophobe renal cell carcinoma: 

Chromophobe renal cell carcinoma is a rare and third most common type of cancer that is pale in colour, like clear cells. ChRCC is darker and contains other features that differentiate it from clear cell RCC.

Chromophobe RCC is associated with Birt-Hogg-Dubé syndrome (a rare genetic condition) and may also linked with other genetic diseases such as multiple endocrine neoplasia type 1 (MEN1). It accounts for a total of 5% (5 cases in 100) of renal cancer cases.

2.1.6 Unclassified RCC: 

Some types of renal cancer do not fit into any category. Because more than one type of cancer is present, doctors label it as unclassified renal cancer carcinoma (RCC).

The NIH reports that unclassified RCC associates with poor clinical outcomes and exhibits unique, extremely aggressive biological behavior. Unclassified RCC is rare and involves only 5% of total cases of renal cell carcinoma. 

2.2 Non-clear cell renal cell carcinomas: 

These comprise all subtypes of RCCs that are not clear cells. Non-clear cell renal cell carcinoma is a group of tumours that includes various histological subtypes, each with unique characteristics including genetic mutation, clinical behaviour, prognosis, and responsiveness to treatment. The subtypes of renal cell carcinoma includes:

• Collecting duct RCC: It is a rare and aggresive type of kidney cancer also known as Bellini duct carcinoma. Thid type of kidney cancer occurs in the collecting duct of the kidney.
• Multilocular cystic RCC: It is a rare, low-grade, and curable type of kidney cancer with  non-specific symptoms. It accounts for total 1–5% of renal cases. 

• Medullary carcinoma (renal medullary carcinoma): Medullary carcinoma is also a rare and most common disease associated with sickle cell trait. It causes blood in the urine and is commonly seen in young people.

• Mucinous tubular and spindle cell carcinoma: It is a rare subtype of renal cancer  that occurs in people who do not carry any sickle hemoglobinopathies. It is twice more common in males as compared to women.

• Neuroblastoma-associated RCC: It is a rare subtype of renal cancer that is linked with renal neoplasia.

2.3 Other Types of Kidney Cancers

Some other types of cancer include transitional cell carcinoma, Wilms tumour, and renal sarcomas. 

Transitional Cell Carcinoma: 

Transitional cell carcinomas (TCCs), also known as urothelial carcinomas, affect only 5 to 10 renal cases (6-7%) out of the total 100. Urothelial carcinoma accounts for 90% of bladder cancer and 7% of all kidney cancers.

Transitional cell carcinoma begins in the lining of the renal pelvis, where the ureters and kidneys meet.

The cells that line the bladder and ureters are known as transitional cells, which make up this lining. When examined closely, cancers that arise from these cells resemble other urothelial carcinomas, including bladder cancer.

Like bladder cancer, cigarette smoking and cancer-causing chemicals such as carcinogens mostly link these diseases.

The symptoms of TCC are similar to those of renal cell cancer, like blood in the urine and back pain.

Doctors use urinalysis, urine cytology, intravenous pyelogram, ureteroscopy, ultrasound, and CT scans to confirm the presence of transitional cell carcinoma.

According to NIH, transitional cell carcinoma shows an improved prognosis. If these tumours are superficial and limited to the ureter or renal pelvis, almost 90% of patients can be cured.

The prognosis for patients with deep malignant tumours that are limited to the ureter or renal pelvis is 10% to 15%. 

Wilms Tumour (Nephroblastoma):

Wilms tumour also known as nephroblastoma, is a rare kidney cancer but mostly affects children of age 3 to 4 (represents only 5%). It is less common after the age of 5 and in adults. 

The cause of Wilms tumour is not clear, but cancer starts during cell changes in DNA. In rare cases, it increases the risk when the affected DNA passes from parent to child.

Black children in North America, Europe, and people with family history of Wilms tumour are more at risk of developing this disease. 

The common symptoms on paediatric include mass in the stomach area, swelling and pain in the stomach, fever, blood in the urine, aneamia and high blood pressure.

Doctors diagnose a Wilms tumour through a physical exam, blood and urine tests, and imaging tests. They treat Wilms tumours using surgical procedures, chemotherapy, and radiation therapy.

Renal Sarcoma:

Renal sarcoma is also a rare type of cancer that starts from blood vessels or connective tissue of the kidneys. It accounts for only 1% of all kidney cancers. Abnormal growth of cells in the connective tissues or blood vessels of the kidneys causes it.

This type of sarcomatous cancer mostly affects people in the older age groups of 50 to 70. The risk factors that increase the chance of developing renal sarcoma include obesity, smoking, acquired kidney disease, hepatitis C, and overuse of painkillers.

The symptoms of renal sarcoma include blood in the urine, pain in the back, general fatigue, low RBC, increased blood pressure, and weight loss.

Doctors usually use X-ray, ultrasound, CT scan, MRI, and positron emission tomography (PET) scan to confirm the diagnosis of renal sarcoma cancer. The treatment for renal sarcoma includes surgery or chemotherapy.

The 5-year survival rate in some patients after conservative surgery of transitional cell carcinoma is 70-90%.

3. Benign (Non-Cancerous) Kidney Tumourss

3.1 Angiomyolipoma

Angiomyolipomas are benign tumours (non-cancerous) that are made up of blood vessels, fat cells  and muscle cells. They are non-cancerous and affect only 0.2-0.6% of people, mostly women. 

If angiomyolipoma increases in size, it causes rupture and bleeding. The cause of angiomyolipoma is sporadic and hereditary. 

Sporadic is the most frequent and usually appears as a single tumour without linking to genetic actors. 

Hereditary causes include gene involvement with genetic predisposition. This  type of tumour can be multiple and grow in both kidneys and results in complications.

Angiomyolipomas are of three types based on the size, location, and type of cell and tissue. It includes

• Classic (triphasic) AMLs: In the classic type of angiomyolipoma, it contains all three types of tissues, including smooth muscle tissue, blood vessel and fat.
• Monophasic AMLs: In monophasic AMLs, it contains only one type of tissue, like smooth muscle or fat.
• Epitheloid Angiomyolipomas: It contains only epitheloid type of cells that line the kidneys blood vessels that are likely to become cancerous. 

Aneamia (due to bleeding), fever, kidney pain, increased blood pressure, nausea and vomiting are common symptoms of agiomyolipomas. Doctors performs CT scan, MRI and ultrasound to diagnose it. Kidney biopsies are also used to confirm the diagnosis of angiomyolipomas. 

According to the NIH, it accounts for only 0.3 to 3% of all renal neoplasms. Angiomyolipomas are frequently observed in middle-aged women with roughly 4:1. It is more common in 80% of adults with tuberous sclerosis complex (TSC). 

3.2 Papillary Renal Adenoma

Papillary renal adenomas are finger-like projections, which differentiates them from other types of renal cancers. Pappilary renal adenomas are benign tumours that are non-cancerous and usually grow slowly. It is a rare, but most common non-cancerous type of kidney tumour that does not show any symptoms.

There are two types of papillary renal adenoma.

• Type 1 Papillary adenoma: Type 1 is more common type of papillary RCC in which the cancer cells are small, uniform and usually grows slowly.
• Type 2 Papillary adenoma: In type 2 papillary adenoma, it includes larger cells that are linked with complex growth patterns while benign in nature. 

They are less than 15 mm in diameter and mostly located in the superficial cortex of the kidneys. Due to their size and benign in nature, they are usually asymptomatic. 

Doctors usually diagnose papillary adenoma incidentally during nephrectomy for another disease. They can also assess it through imaging techniques such as CT scans, MRIs, or ultrasounds.

The prognosis of papillary adenoma depends on the stage of diagnosis with better survival rate. 

Reccurence of papillar adenoma is rare after surgery. The NIH highlighted the 5-year survival rate of papillary renal adenoma after diagnosis. It is better than 80% in stage 1 and the rate drops to 8% in stage 4.

Papillary renal adenomas, like other malignant renal tumors, do not spread to other parts due to their benign nature and do not affect renal function.

3.3 Oncocytoma

Oncocytomas are common benign (non-cancerous) cancers that derives from the renal tubules (intercalated kidney cells).  It accounts for 3 to 7 percent of renal neoplasms. The word oncocytoma is a medical term used for tumours made of oncocytes (epithelial cells with excessive mitochondria). It can occur in one or both kidneys and is commonly asymptomatic. 

Renal oncocytomas can affect people of all ages, races and genders. It is more common in people assigned male at birth (AMAB) and age over 60 years. It can also occur in people with genetic condition such as Birt-Hogg-Dubé syndrome. 

The type of oncocytoma depends on the number of chromosome rearrangements.

• Type 1 Oncocytoma: Type 1 oncocytoma has no gross chromosomal loss and CCND1 rearrangement.
• Type 2 Oncocytoma: Type 2 has chromosome 1 loss, and may also have sex chromosome loss 

Oncocytomas usually range from 3 to 7 cm in size but may vary. The exact cause of renal oncocytomas is not known. People with inherited gene change or mutation are at higher risk of developing this type of cancer in one or both kidneys. 

It mostly occurs in the renal cortex or medulla region. The symptoms may include blood in the urine, flank pain, or a feeling of lump in the affected kidney. It is diagnosed through imaging tests (CT and MRI scans) and kidney biopsy. 

The renal oncocyotma that does not grow or cause problems requires no treatment. If it causes symptoms and complications, doctors would recommend surgery to remove the mass of the tumour (partial nephrectomy) or complete kidney (radical nephrectomy).

The National Organization for Rare Disorders (NORD), share that renal oncocytomas are rare renal cancer that make up roughly 3-7% of all kidney tumours, with an estimated 0.5-1.5 cases per million annually.

Imagining characteristics helps to distinguish oncocytoma from RCC. This table highlights the difference between renal cell carcinoma (RCC) and oncocytoma upon imagining.

Imaging Test	Oncocytoma	Renal Cell Carcinoma (RCC)
CT Scan	Tumours seen as well-circumscribed and round mass -Homogeneous texture -No significant calcification	Seen as irregular borders or heterogeneous texture due to necrosis or hemorrhage Heterogeneous with larger lesions Central scar less common (can appear in chromophobe RCC) May show calcifications in rare cases
			MRI	Low signal intensity on T2-weighted images Uniform enhancement after contrast	High signal intensity on T2-weighted images Irregular enhancement after contrast
						PET Scan	Lower metabolic activity	Higher metabolic activity due to increased glucose uptake
			Prevalence of Central Scar	Present in ~33% of cases	Rare (can appear in chromophobe RCC)
Calcifications	Rarely present	Calcifications more commonly seen

Table: 01: Difference between oncocytoma and RCC

4.1 Signs and Symptoms of Renal Cancer

Common Symptoms: 

At initial stages, the renal cancers do not show early sign and symptoms. Large tumours can cause more severe symptoms and their size and stage are frequently correlated with the degree of symptoms. As the severity of renal cancer increases, it shows the following late signs.

• Loss of appetite: It results from a tumour that may affect metabolism and decrease appetite.
• Fatigue and Tiredness: Due to lower production of red blood cells, which decreases the oxygen to muscles, this results in fatigue and tiredness.

• Bone Pain: When renal cancer spreads to bones, it causes destruction and results in severe bone pain and may result in fractures.

• Low-grade fever: Some types of cancers can cause inflammation that results in low-grade fever.
• High Calcium: Sometimes, renal cancer releases a hormone that disrupts the calcium levels in the blood and causes hypercalcaemia.
• Increased blood pressure: As kidneys are responsible for controlling blood pressure, some renal cancer may disrupt its normal functioning and cause hypertension. 
• Palpable lump: Feeling of lump or mass in the abdomen or lower back.

Specific Symptoms:

These are some specific alarming symptoms of renal failure that requires immediate consultation with a doctor.

Hematuria (Blood in the urine): It is due to the increased size of the tumor, which results in bleeding. The urine appears red, pink, or cola-coloured due to the mixing of blood.

Flank Pain: Flank pain is another symptom of renal cancer caused by a tumour in the kidney. When the size of the tumour increases, it pushes on the other organs of the body, resulting in severe flank pain.

Unusual weight loss: The lack of appetite and cancer impact on overall health and results in unexplained weight loss. It is an alarming symptom that needs to be addressed immediately. 

The American Cancer Society states that doctors find about 40 to 50% of kidney cancers incidentally during routine exams or scans. Larger tumours cause more severe symptoms, further compromising the quality of life, as tumour size and cancer stages link to the degree of symptoms.

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4.2 How Serious is a Tumor on the Kidney?

The seriousness of kidney tumour depends on various factors such as benign or malignant, size of tumour, and stage of diagnosis. The benign tumour are non-cancerous, generally smaller and doesn’t spread to other parts of the body. 

The size of the tumour helps to assess and determine the severity of renal cancer. A smaller tumour remains in the kidney, while a larger tumour affects other organs and causes inflammation.

Better management of cancer is achieved through early diagnosis of tumors, compared to dealing with complications that come with later diagnoses.

The malignant tumours are more serious, spreadable and causes complications to other organs such as the lungs, liver, and bones. It declines kidney functioning and leads to chronic conditions such as renal failure in severe cases.

The American Urological Association (AUA) stated that doctors frequently treat tumors under 4 cm with strict observation, especially in elderly individuals, as they are less aggressive. Tumours greater than 7 cm have a higher chance of being malignant, impairing kidney function, and spreading to other organs.

According to the American Cancer Society, the early diagnosis of renal cancer has a favorable diagnosis. The 5-year survival rate at stage 1 is 90%, stage 3 is 75%, and at stage 4 the rate decreases up to 15%.C

5. Causes and Risk Factors

As there is no exact cause of cancer, but still there are many risk factors that increases the chance of renal cancer. The primary cause of kidney cancer risk factors includes: 

Lifestyle Factors

Smoking: 

Smoking is a significant risk factor for developing renal cancer. Tobacco introduces carcinogens that are filtered by the kidneys. The excessive use of tobacco intake damages kidney cells that lead to mutations in the DNA and causes cancer.

According to Centers for Disease Control and Prevention (CDC), about 36% current smokers are at higher risk of developing renal cell carcinoma (RCC) as compared to non-smokers. 

Obesity: 

Obesity is directly linked with cancer. The increase in BMI values disrupts the hormonal balances especially insulin and insulin growth hormone. It results in cancerous mutations and contributes as a risk factor for developing kidney cancer. 

High Blood Pressure (Hypertension): 

The consistent high blood pressure puts strain on the kidneys that damages kidney cells and causes cancer. The NIH highlighted that HTN people with controlled blood pressure had a 60% increase in renal cancer risk.

Genetic and Hereditary Factors:

Family History: 

People with a family history of renal cancer are more prone to developing kidney cancer due to inherited gene mutations passed from parents to children. So, family history is also a risk factor for causing renal cancer.

According to the NIH, about 5–8% of kidney cancers are caused by hereditary.

Specific Genetic Syndromes:

The other risk factors of renal cancer also includes

Von Hippel-Lindau disease (VHL): 

It is a hereditary disorder that increases the risk of forming non-cancerous tumors in blood vessels, especially in the eyes and brain. VHL is directly involved in the formation of cysts and tumours in the kidneys. 

Several studies showed the direct relationship of developing cancer among smokers. A meta-analysis published in Cancer Epidemiology, Biomarkers & Prevention (2018) highlighted that smokers are 1.5 to 2 times more likely to develop renal cell carcinoma (RCC) than non-smokers.

The risk of cancer increases with the number of cigarettes smoked and the time frame of smoking.

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC): It is a hereditary disease that includes the formation of benign tumors with smooth muscle tissue (leiomyomas) in the skin and the uterus of females, causing renal cancer. According to Medline Plus, about 10-16% get renal cancer due to HLRCC. 

Birt-Hogg-Dubé (BHD) Syndrome: It is a disease linked with the development of renal cell carcinoma (RCC), caused by mutation of germline in the folliculin gene. This syndrome is directly involved in skin lesions and lung cysts and increases the risk of kidney tumors.

According to the NIH, about 25–35% of people with Birt-Hogg-Dubé (BHD) syndrome are at higher risk of developing renal tumours.

Cowden Syndrome: Cowden syndrome is a rare inherited condition in which the benign tumour grows in different parts of the body and increases the risk of certain cancers, such as renal cancer. The American Cancer Society reported that the risk of developing kidney cancer with Cowden syndrome is 2%–5%.

Tuber sclerosis complex: It is a genetic disorder that causes seizures, intellectual disabilities, and the formation of benign tumors in various organs of the body, such as the kidneys, lungs, brain, skin, and heart, due to mutations in the TSC1 or TSC2 genes.

BAP1 Tumor Predisposition Syndrome: It is also a rare inherited disease that is caused by the mutation of BAP1 gene. This mutation increases the risk of developing other types of cancer, such as skin, eye, mesothelium, and kidney cancer. According to NIH, the percentage of people developing RCC with BAP1 tumour predisposition syndrome is only 1-1.5%.

Hereditary Paraganglioma-Pheochromocytoma Syndromes: It is an inherited disease that is linked with the growth of tumors in paraganglia structures (ganglia). It increases the risk of developing clear cell carcinoma and tumour formation in blood vessels. The NIH reported only 3% of cases cause renal cancer in adults due to paraganglioma-pheochromocytoma syndromes.

Environmental and Occupational Exposures:

Radiation therapy: Previous radiation exposure also increases the risk of renal cancer. Women who was treated with radiation for reproductive organs are at inclreased risk of having renal cancer.

Chemical Exposures: The exposure to certain chemicals such as trichloroethylene, benzene, heavy metals (cadmium, lead), creosote, or asphalt increases the risk of kidney cancer due to carcinogens. 

People who work in industries and handle hazardous chemicals are at increased risk of developing renal cancer. According to NIH, occupational chemical exposures account for 2–8% of developing renal cancer.

Chronic Kidney Conditions:

Long-Term Dialysis Treatment:

People on long term dialysis are at increased risk of developing kidney cysts and renal cancer. As dialysis cannot work as normal kidney function, it increases the stress on the kidneys.

Chronic inflammation and the increased risk of renal cancer result from the long-term dialysis causing cellular changes and oxidative stress. 

According to the NIH, people on long term dialysis are 3–10 fold higher at risk of developing renal cancer as compared to the normal population.

Chronic Kidney Disease: 

Persistent decline in kidney function is another risk contributing to renal cancer. The reduced functioning of kidneys compromises blood filtration, which results in the accumulation of toxins such as carcinogens.

CKD weakens the immune system against toxic substances that increase the risk of renal cancer. In adults and older people, chronic kidney diseases cause 14.5% percent of renal cancers, according to the United States Renal Data System (USRDS).

This rate increases with age and affects about 23.9% of people over 85 years and older. ​

Immunosuppressant Medications: 

Immunosuppressant medicines are commonly prescribed after kidney transplant to prevent organ rejection. It suppresses the immune system and weakens the ability to fight abnormal cell growth, which results in an increased risk of the development of renal cancer.

Some immunosppresants, such as calcineurin inhibitors and corticosteroids, are known to have a higher risk of developing renal cell carcinomas.

Surgical Intervention: 

The surgical removal of a kidney in renal cancer, known as nephrectomy, also increases the risk of developing cancer in the remaining kidney. It is known as compensatory renal growth that causes instability of genes and causes renal cancer in the remaining one. 

After nephrectomy, the remaining kidney has to work harder to make up for the loss. It led to cellular changes due to stress on the kidneys. Over time, this stress on the remaining kidney may increase the risk of cancer development, especially in those who have already suffered from kidney cancer.

Preventive Measures: 

Managing chronic kidney disease (CKD) and ensuring kidney health is necessary to lower the risk of kidney cancer. Effective management involves controlling underlying conditions such as hypertension and diabetes, which are major risk factors for both kidney disease and cancer. 

Furthermore, preserving kidney function through lifestyle modifications like dietary changes, staying well-hydrated, and avoiding harmful substances can minimise the chances of kidney damage and the potential development of renal cancer.

Genetic Mutations and Hemoglobinopathies:

Gene Changes (Mutations):

Genes contain all functional information, and changes in certain types of genes can cause renal cancer. Genetic changes in specific genes also contribute to the development of renal cancer. The mutations disrupt the normal functioning of cells and lead to abnormal growth, forming a tumour in the kidney. 

For example: Mutation in gene VHL disrupts the functioning of degraded hypoxia-inducible factor (HIF) that results in tumour formation. The other mutations in the FH, FLCN, SDHA-D, and BAP1 genes also result in abnormalities that promote tumour growth. 

According to NIDDK, these mutations contribute to genetic instability, which results in the progression of kidney cancer by disrupting normal cellular processes​.

Sickle Cell Trait and Disease:

Sickle cell trait is a haemoglobinopathy (genetic condition) that increases the risk of kidney complications, including hematuria, reduced urine output, and a rare form of kidney cancer known as renal medullary carcinoma.

The researches of USRDS has shown that people with sickle cell trait or disease have an increased risk of renal failure, and those with sickle cell trait specifically are at increased risk of developing kidney cancer due to chronic medullary stress and damage.

6. Diagnosis and Renal Cancer Stages

6.1 How is Kidney Cancer Diagnosed?

The diagnosis of renal cancer usually starts with a physical examination and medical history. These tests and procedures are used to confirm the diagnosis of renal cancer. 

Blood and Urine Tests: 

In blood tests, doctors observe the number of red blood cells in the body. High values of creatinine, blood urea nitrogen (BUN), and calcium show impaired functioning of the kidneys. In a urine sample, blood, bacteria, and cancer cells indicate kidney cancer. Haematuria (blood in the urine) is linked with renal cell carcinoma. 

Imaging Tests: 

When kidney cancer is suspected, imaging tests such as CT scans and MRIs are performed to confirm it. Ultrasound identifies any irregularity in the kidney. A CT scan provides detailed images to assess the size of the tumour. When CT scans do not provide a clear result, an MRI is performed to evaluate the mass in the tumour.

Biopsy: 

In a kidney biopsy, doctors remove a piece of kidney tissue for testing purposes in a lab. They insert a thin needle into the kidneys or other parts of the body, such as lymph nodes.

Doctors remove a sample of tissue with the help of a needle. Kidney biopsies are usually not the first line of diagnosis for renal cell carcinoma. Doctors perform kidney biopsies when imaging tests do not provide clear results and the required information.

Nephrectomy: 

Nephrectomy is the surgical removal of the kidney. It plays an essential role in diagnosing kidney tumours when imaging and biopsy results are insufficient. During nephrectomy, the surgeon examines a tissue from the removed kidney pathologically to determine if the mass of the tumour is cancerous or not. It also helps to identify the type and to assess the stage of cancer.

Diagnostic Criteria: 

The lab interprets the results of the diagnosis from biopsy samples. When they observe cancer cells in a kidney biopsy, they perform further biochemical tests, such as immunohistochemistry (IHC) and genetic and molecular testing, to detect the type and characteristics of renal cancer.

6.2 What are the Kidney Cancer Stages?

Kidney cancer stages depend on the location and size of the tumour, the extent of affected lymph nodes, and the degree to which the cancer spreads (TNM). Lymph nodes are small filters that prevent germs and cancer cells. CT scans, MRIs, and biopsies are used to determine the stage of renal cancer. 

Many staging methods exist for cancer, and the TNM system is the most widely used and practical approach for most cancer types.

In the TNM system, doctors assign a number or letter to describe the tumor (T), node (N), and categories of metastasis (M) to identify the overall stage of the cancer.

• T refers to primary tumour (T)
• N refers to the cancer spreading to the nearby lymph nodes (N)
• M tells whether the cancer has spread (metastasized) to other parts of the body (M)

These are the stages of renal cancer depending on the tumour size, location, and involvement of lymph nodes (TNM) and other tissues:

Stage	Tumor Size	Lymph Node/Other Tissue Involvement	Location
Stage I	7 centimeters (cm) or smaller	No spread to lymph nodes or other tissues	Limited to the kidney
Stage II	Larger than 7 cm	No spread to lymph nodes or other tissues	Limited to the kidney
Stage III	Any size	May involve nearby lymph nodes, but no distant metastasis	Metastatic, spread to major blood vessels (renal vein or inferior vena cava) or tissue surrounding the kidney
Stage IV	Any size	Involves distant lymph nodes, adrenal gland, or other organs (lungs, bones)	Metastatic, spread outside the kidney (adrenal gland, distant organs)

The pathologists grade the tumours, assigning a number to indicate the appearance of the tumour's abnormal cells and signifying the expected growth rate of the tumour. High-grade tumours are those whose cells divide quickly and don't resemble normal cells.

Compared to low-grade tumours, high-grade tumours typically develop and spread more quickly. 

Clinical staging gives an idea about the prognosis of renal cancer because the survival rate depends on the stage of kidney cancer at the time of diagnosis.

6.3 Detailed Breakdown of Kidney Cancer Stages

In stage 1 renal cancer, the size of the tumour is usually 7 cm (2.8 inches) or smaller in diameter. These tumours are localised and confined to the kidney without disrupting surrounding kidney tissues, lymph nodes, or other organs. 

The small size tumour does not show any visible symptoms. Stage 1 kidney cancer is easily diagnosed through ultrasounds, CT scans, and MRIs. This stage has a high survival rate and prognosis due to its early diagnosis. 

In stage 1, the doctor treats the condition with a partial nephrectomy, removing the tumour or a smaller portion of the surrounding kidney tissue.

For older patients or patients with other health complications, doctors use active surveillance to monitor tumours through regular imaging tests.

According to Cancer Research UK, the 5-year survival rate of stage 1 is 90%. It is treatable due to its fixed location, early diagnosis, and smaller size. 

6.3.2 Stage II: Larger Tumours Still Localized

In stage 2 kidney cancer, the size of tumours is greater than 7 cm (2.8 inches). They are also limited to the kidneys and do not spread to other parts of the body. If not treated, the increased size of the tumour is at higher risk of invasion into nearby tissues. 

Stage 2 shows symptoms due to its larger size, such as blood in the urine, a feeling of palpable mass in the abdomen, or flank pain. If symptoms become visible, it is diagnosed through imaging tests. 

Stage 2 renal cancer is treated with radical nephrectomy, in which the kidney is removed to treat the cancer. 

The Cancer Research UK highlighted the 5-year survival rate of stage 2 renal cancer is 75%, depending on factors such as the health of the patient and early treatment.

6.3.3 Stage III: Spread to Nearby Tissues or Lymph Nodes

In stage ||| of renal cancer, the tumour size can be any, and it spreads from lymph nodes to blood vessels. The cancer may also spread near the kidney (renal vein or vena cava) to the fat around the kidney structure.

In stage 3 of renal cancer, the symptoms become more noticeable and severe. The symptoms of stage 3 cancer include flank pain, blood in the urine, and weight. The other symptoms also involve fatigue and swelling due to the involvement of major blood vessels in renal cancer. 

The prognosis of stage 3 is moderate due to its severity. The survival rate depends on the size of the tumour, the involvement of lymph nodes, and the overall health of the patient. According to Cancer Research UK, the 5-year survival rate for stage 3 cancer is 75%.

The affected kidney and surrounding tissues are removed in a radial nephrectomy to treat stage 3 renal cancer. It also involves dissection of lymph nodes to address any cancer spread in nearby nodes. Patients with stage 3 renal cancer may use targeted therapy and immunotherapy to prevent recurrence and improve overall health.

The results from clinical trials have concluded that about 38–70% of patients with early stages of renal cancer are curable with surgery. However, the chances of recurrence are higher due to the spread of cancer outside the kidneys. 

6.3.4 Stage IV: Metastasis to Distant Organs

Stage 4 of renal cancer is severe and complicated. In stage 4, the cancer has spread outside the kidney and lymph nodes to other organs. The organs that can be affected with stage 4 renal cancer are the lungs, bones, liver, and brain. 

Stage 4 renal cancer shows more severe symptoms. It includes persistent pain, extreme fatigue, shortness of breath, or neurological issues if the brain is affected. 

The prognosis of stage 4 is generally poor, with lower survival rates as compared to other stages. According to Cancer Research UK, the survival rate for stage 4 renal cancer is reduced to only 15%.

For the treatment of stage 4, multiple therapies such as targeted therapies, immunotherapies, and palliative care are used. The treatment of these therapies focuses on managing the disease, slowing the progression of cancer, and improving overall quality of life. 

The management of stage 4 renal cancer focuses on prolonging life and improving quality of life. Besides therapies, proper counselling sessions, regular monitoring, and adjustment to the treatment plan help in the better management of the symptoms. 

The National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) suggest that combination therapies, such as immunotherapy combined with targeted therapy, provide the most favourable outcomes for patients with Stage IV cancer.

Current clinical trials are investigating new drug combinations to assess their effectiveness in prolonging survival and enhancing quality of life.

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6.4 Implications of Staging: Treatment Options and Prognosis

The treatment of renal cancer depends on the stage of kidney cancer, the grade of the tumour, the patient’s age, and overall health. 

 

Based on stage-specific treatment, each stage is treated with a different method due to its localisation and severity of the disease. 

 

• Stage 1 and 2: In stages 1 and 2, the patient is treated with radical or partial nephrectomy. As the tumour of stages 1 and 2 is localised within the kidneys, it is curable with the surgery. 

• Stage 3: In stage 3, the tumour is not localised and metastasised in lymph nodes; it is treated with radical nephretomy and lymph node dissection, often followed by adjuvant therapies (immunotherapy).

• Stage 4: It is the advanced stage of cancer that is treated with systemic therapies, including targeted therapies and immunotherapy. With a multimodal approach, palliative surgery is frequently used for managing symptoms and promoting slower disease progression.

The survival rate is the percentage of patients who survive for at least five years after the diagnosis of renal cell carcinoma. The stage of the cancer at the time of diagnosis affects the survival rate. 

 

According to NIH, the 5-year survival rate of renal cell carcinoma is 

 

• Stage 1: 90% 5-year survival rate
• Stage 2: 50% 5-year survival rate
• Stage 3: 30% 5-year survival rate
• Stage 4: 5% 5-year survival rate

 

The effectiveness of treatments depends on the stage of cancer. In cases of localised kidney cancer (Stages I and II), surgery options are effective and offer a complete cure.

In more advanced stages (III and IV), doctors consider systemic therapies effective and use them in combination (such as immunotherapy and targeted therapy). The overall success rates are lower due to the complexities associated with the renal cancer.

The staging information guides clinical decisions to choose treatment goals, select an appropriate treatment plan, and highlight the potential risk and benefits to achieve better results and prolong quality of life.

 

According to the NIH, the early diagnosis, i.e., stages 1 and 2, has a better treatment option with an improved outcome as compared to stage 4, with a poor prognosis and a lower survival rate. 

7. Management and Treatment

Kidney cancer is treated with the following methods, depending on the stage and severity of the disease. The treatment options for renal cancer include

Surgery: 

The surgical method is the most common and effective treatment option for kidney cancer. Partial nephrectomy and radial nephrectomy are two ways to treat tumours of the kidney.

Surgical Approaches: 

There are many surgical approaches to treat renal cancer. It includes open surgery, laparoscopic surgery and robotic-assisted surgery. 

Nonsurgical Options: 

Non-surgical options include ablation (radiofrequency ablation (RFA) or cryoablation), radiation therapies, or drug therapies. 

Combination Therapies: Combination therapies are also used to treat advanced stages of renal cancer, such as systemic therapies (targeted therapy or immunotherapy) in combination with surgery or radiation. The multimodal approach is also helpful in managing symptoms, tumour growth, and increasing survival rate. 

Personalised Treatment Plans: 

Personalised treatment plans are effective and boast engagement in the treatment process. It helps build trust and satisfies patients in their health journey. Each renal patient requires a personalised treatment plan because every patient suffers from different sizes of tumours, fatiqgue, and other complications depending on the age and health condition.

According to the NIH, robotic-assisted surgery offers quicker recovery times and less blood loss compared to open surgery, while maintaining similar outcomes of cancer control. 

7.2 Surgery

Radical Nephrectomy:

In radical nephrectomy, the surgeon removes the entire affected kidney along with the fatty tissue, Gerota’s fascia, and nearby lymph nodes. If the cancer is spreading rapidly, the surgeon also removes the adrenal gland located above the kidneys.

While radical nephrectomy is effective in removing the cancerous part of kidney and reduces the risk of recurrence, it leaves the patient with only one functioning kidney.

Partial Nephrectomy:

In a partial nephrectomy, surgeons remove only the cancerous part of the kidney. Studies have shown that partial nephrectomy has long-term effects because surgeons remove the whole kidney. This approach is beneficial in the early stages of cancer as it keeps the remaining kidneys working. 

Indications for Each Type: 

Radical nephrectomy is suitable if the tumour is bigger in size and there is a higher chance of spreading cancer to other parts of the body.

Partial nephrectomy is appropriate if the kidney tumour is smaller than 10 cm and the person has reduced kidney function, such as whether they are at risk for chronic renal disease, have tumours in both kidneys, only have one functioning kidney, or have a genetic disorder that increases the chances of developing additional kidney tumours in the future.

Recovery and Risks: 

In radical nephrectomy, the patient is fully recovered in 4-6 weeks. During a partial nephrectomy, the hospital stay is shorter, about 1-3 days, and recovery takes about 3-5 weeks. The associated risk of radial nephrectomy includes bleeding, infection, and long-term loss of kidney function.

The potential complications of partial nephrectomy may involve incomplete tumour removal, infection, or injury to surrounding tissues. 

Long-Term Effects: 

The primary long-term effect of radical nephrectomy is a decrease in kidney function because the patient will depend solely on the remaining kidney.

However, many individuals can live a normal life with one kidney, there is an increased risk of developing chronic kidney disease (CKD) or other renal complications.

In partial nephrectomy, it reduces the chances of CKD. However, there is a little chance of cancer recurrence if any malignant tissue is not completely removed.

According to the NIH, both radical and partial nephrectomy have a higher success rate and long-term survival rates to treat early-stage kidney cancer.

7.3 Surgical Approaches

Open Surgery:

Open surgery is a traditional method to remove a tumour of the kidney. Surgeons make a large incision of about 10-20 cm in the abdomen to remove a large tumor from the kidney.

It takes 6-8 weeks for the patient to recover, but the procedure is linked with post-operative pain and a higher risk of infection or bleeding.

Laproscopic Surgery:

In laparoscopic surgery, the doctor uses instruments to insert a camera (laparoscope) and surgical tools in the abdomen through several small incisions of about 1-2 cm in size.

This minimally invasive approach leads to less scarring, quicker recovery time, and less postoperative pain. The patient usually recovers within 3-4 weeks. It is not suitable for treating large tumours in complex cases.

Robotic Surgery: 

In robotic-assisted surgery, a surgeon uses a robotic system equipped with precise instruments to perform the procedure, which is a more advanced form of laparoscopic surgery.

The surgeon removes a small portion of the normal kidney along with the tumour. The remaining healthy kidney tissue is spared and surgically repaired to allow normal blood and urine flow.

It is beneficial for partial nephrectomy and complex cases to remove the tumour and lower the damage to surrounding tissues. This treatment method is costly and not affordable to all hospitals.

Choosing the Right Approach

These are some factors that help you choose the right surgical approach.

• Size of tumour and its location: Large tumours require open surgery, while laparoscopic or robotic surgery is ideal for small localised tumours. 
• Patients' overall health: For older patients, minimally invasive surgeries are usually preferred due to compromised health conditions and reduce the surgical risk.
• Surgeon expertise and equipment availability: The availability of robotic systems and expert surgeons also play a major role in choosing the right approach.

7.4 Nonsurgical Options

Ablation Techniques: 

Ablation is a non-surgical method in which extreme cold or radio waves are used to destroy kidney cancerous cells. It includes cryoablation and radiofrequency ablation. 

Radiation Therapy: 

Radiation therapy is a powerful method to treat cancer. External beam radiation therapy and internal radiation therapy is the most common type of radiation therapy. The radiation therapy depends on the type of cancer.

It is a reliable and effective cancer treatment that shirnks the tumour before the cancer surgery. It also destroys remaining cancer cells after surgery. 

Althought, this treatment is effective but it increases the risk of developing different cancer in the future. 

Targeted Drug Therapy: 

It is a drug therapy that blocks certain types of cancer cells to thrive. It targets the genetic mutations which turn healthy cells into cancer cells.

Targeted drug therapy is used as a front-line or initial treatment that can be combined with other treatments to get the required outcome.

Angiogenesis inhibitors, proteasome inhibitors and signal transduction inhibitors are some examples of targeted drug therapy. 

Immunotherapy:

In immunotherapy, certain medicines are prescribed to boost the immune system. These help recognise cancerous cells and destroy them more effectively.

They are prescribed as standalone treatments or along with surgery. 

Chemotherapy: 

Chemotherapy is a standard treatment for kidney cancer. In chemotherapy, doctors use certain drugs to destroy cancer cells and prevent tumour growth.

They also combine it with other treatments, such as radiation therapy or surgery. This treatment is effective and usually administered intravenously, but it causes many side effects.

7.4.1 Ablation

 

7.4.1.1 Cryoablation

Methodology: 

Cryoablation is a treatment process that uses extremely cold gas to freeze and destroy abnormal cells. It can be performed topically, percutaneously, or surgically. 

Procedure Details:

Topical cryoablation can be performed during a regular visit. It is not painful, and the patient is not asked to change clothes or take painkillers.

During cryotherapy, a surgeon uses a needle-like hollow applicator called a cryoprobe. It contains extremely cold gases, such as

• Nitrogen in liquid form.
• Nitrous oxide in liquid form.
• Compressed argon in gas form

During the procedure, the doctor uses imaging technology to locate the exact area of treatment. The specialist applies the cryoprobe to the diseased or abnormal tissue for a short time, ranging from a few seconds to a few minutes.

The extreme cold at the tip of the cryoprobe freezes and eliminates the unhealthy cancerous tissue. The doctor applies the cryoprobe to the affected area multiple times to achieve the required outcome.

Once the doctor completes the cryoablation procedure, they remove the cryoprobe and close the incision. The entire procedure can take from a few minutes for small skin issues to several hours for open cryosurgery.

Effectiveness: 

As compared to open surgery, cryosurgery is usually preferable due to the following reasons:

• Fewer side effects and less scarring as compared to open surgery
• Easiest recovery
• More affordable
• More safer and lower chances of infection

Surgical cryoablation generally ensures safety, but it has some limitations.

• Bleeding
• Damage to surrounding organs
• Fluid accumulation in nearby organs, such as the lungs
• Nerve damage leading to numbness or weakness
• Infection from any opening in the skin

Compared to other surgical procedures, the overall survival rate of cryoblation rate was 87%, the cancer-specific survival rate was 100%, and the recurrence-free survival rate was 88% in renal patients without residual disease

Recovery Process:

The recovery time of cryotherapy depends on the type of procedure.

• Topical cryotherapy: It ensures the fastest recovery and the patient is able to continue their normal activities right after the surgery.
• Percutaneous cryosurgery: Percutaneous surgery requires 1 to 3 days to recover.
• Surgical cryoablation: In surgical cryoablation, doctors restrict the patient from lifting anything for 72 hours and limit normal activities for 7 to 10 days. 

After surgery, they advise the patient to take bed rest for at least 4 hours. Patients report no immediate complications, and they can eat or drink after one hour.

Doctors recommend painkillers if the patient feels pain in the surgery area. A follow-up is scheduled after one month.

Suitability: 

Before the procedure, the patient undergoes an MRI and CT scan to ensure whether a person is suitable for cryoablation or not. Patients with 1A or 1B kidney cancer are suitable candidates for cryobalation. Doctors also consider these factors before suggesting cryobalation as a treatment option to renal cancer patients. 

• Older age patients or with medical conditions
• People with poor kidney function or having one kidney
• The size of the tumour should be 3 cm or less.
• Tumours located at the back of the kidney are easier to treat as compared to those located at the front of the kidney. 

The Medical News Today highlighted that several studies concluded cryoablation for the treatment of kidney cancer is a safer and more effective treatment option with limited side effects.

7.4.1.2 Radiofrequency Ablation

Methodology:

Radiofrequency ablation uses high-energy radio waves (heat) to destroy cancerous cells in the kidneys. In this procedure, doctors uses radio waves to generate a current, also known as radiofrequency neurotomy.

The heat destroys the area of the nerve and stops it from sending pain stimulation signals to the brain. It treats cancerous cells (tumours) and provides lasting relief from chronic pain.

Procedure Details: 

In radiofrequency ablation, the surgeon administers local anesthesia to numb the area of surgery. The surgeon inserts a thin, needle-like probe into the tumour and uses a CT scan or ultrasound to ensure precise placement.

Once the probe is correctly positioned, an electric current flows through its tip. It generates heat and kills the cancerous cells of the tumour.

Effectiveness: 

Radiofrequency ablation has shown high success rates in treating small kidney tumours. The procedure takes 15 minutes to 2 hours depending on the tumour size, location and number of treatments performed. According to the NIH, the primary success rate of radiofrequency ablation is 95.5% and the overall technical success rate is 98.5%.

Recovery: 

The recovery from radiofrequency ablation is quick and patient can resume their normal routine within a few days. Pain relief in some people is immediate, occurs within 10 days, and may take 3 weeks. Fever, nausea, mild pain or discomfort in the surgery area are some common complications of radiofrequency ablation. 

Suitability: 

Radiofrequency ablation is suitable for the following candidates:

• Having small tumours (less than 4 cm).
• Are not good candidates for surgery due to other health conditions.
• Patients who want less invasive options to avoid more extensive surgery.

According to the NIH, RFA has an outstanding local control rate for renal cell carcinomas, ranging from 91 to 100%. Although tumour recurrence is slightly higher than with surgery, RFA is a good alternative for treating small renal tumours because it is effective and provides long-term results.

7.4.2 Radiation Therapy

Methodology: 

In radiation therapy, a special machine creates and focuses beams of radiation to treat the kidney tumour. It directs high-energy waves that shrink and kill the tumour cells.

Types of Radiation Therapy: 

• External beam radiation (ERBT) and brachytherapy are the types of radiation therapy. In ERBT, health care professionals deliver radiation from outside the body to the patient’s cancer site. Cobalt-60 machines, linear accelerators and neutron beam machines are some systems used for external beam therapy to treat cancer.
• In internal radiation therapy (brachytherapy), the radiation sources in the shape of wires, seeds (or moulds), or rods are positioned as close to the tumour location or directly into the tumours.

Applications: 

Radiation therapy is suitable if 

• There is more than one tumour, or the cancer has spread
• A person is not healthy or unable to have surgery due to other health complications.
• Some radiation therapy is required before ablative procedures.
• To relieve palliative symptoms
• If the other treatments are not effective. 

Effectiveness: 

According to the NIH, the success rate of radiation therapy in treating renal cell carcinoma is 90–98%. Besides success rates, there are some limitations linked with radiation therapy. It includes

• Damage to other surrounding tissues or organs depends on the location of the tumour. 
• Radiation therapy is only used for tumours that are visible on CT scan
• Lower ability to kill all cancerous cells in large tumours
• Less effective in treating tumours with poor blood supply
• Not suitable for patients with specific conditions or who have done radiation in the same location before.

Side Effects: 

The short-term side effects are mild and usually disappear within a few months after treatment. It includes nause, vomiting, redness, irritation, sunburnt skin, hair loss at the site of treatment, and fatigue. 

The long-term side effects may appear after some months or even years after the treatment. It increases the risk of heart disease, persistent fatigue, and developing second cancer.

Radiation therapy is an effective treatment to treat renal cell carcinoma (RCC), with high rates of local control and low toxicity risks. The NIH reported the success rate of radiation therapy for treating renal cancer is 90-98%.

7.4.3 Targeted Drug Therapy

Mechanism of Action: 

Molecular targeted therapy, also known as targeted drug therapy, stops the growth of cancerous cells and limits the harm to normal cells. The drugs target specific molecules to send signals to inform whether to grow or divide. 

Targeted drug therapy is beneficial to

• Control or kill cancerous cells of tumours
• Relive pain or control the symptoms of advanced kidney cancer

Common Targeted Drugs: 

The targeted drugs treat kidney cancer by inhibiting proteins known as tyrosine kinases within cancer cells. These proteins typically promote cell growth or help form new blood vessels that supply the tumour.

Tyrosine kinases are proteins that targeted drugs, such as Sunitinib and Pazopanib, inhibit. These medications are known as tyrosine kinase inhibitors or TKIs.

Effectiveness: 

The NIH states that patients tolerate targeted drugs well, and clinical trials show that these drugs improve the quality of life and extend the survival of patients with renal cancer.

For example, doctors use the Sunitinib drug as a first-line treatment for metastatic renal cancer.

Side Effects:

Each drug of targeted therapy shows potential adverse reactions. These are some common side effects of targeted therapy.

• Diarrhea
• Dryness of skin
• Extreme sensitivity to light
• Increased blood pressure
• Loss of hair colour
• Nail changes
• Increased liver enzymes
• Damage to heart muscles and arrhythmias
• Neurological changes
• Interstitial lung disease
• Delay in wound healing and blood clotting

Combination with Other Treatments: 

When combined with other traditional treatments, targeted drug therapy has a synergistic effect, like chemotherapy, surgery, or radiation therapy. 

For Example:

Clinical trials of targeted drug therapy, such as Sutinib, have shown improved survival rates compared to other treatment methods, such as interferon therapy. 

7.4.4 Immunotherapy

Immunotherapy uses the body’s immune system to boast and destroy cancerous cells. In renal cancer, checkpoint inhibitors like nivolumab block proteins (e.g., PD-1 or PD-L1) that prevent immune cells from attacking cancer. They treat different types of cancer, including kidney cancer. 

Doctors administer immunotherapy intravenously (IV) to renal patients once, weekly, or monthly in a cycle. Immunotherapy depends on the type and stage of cancer and the body’s response to the immune system.

Types of Immunotherapy: 

These are the types of immunotherapy that are responsible for treating different types of cancer. It includes

• Checkpoint inhibitors
• Adoptive cell therapy (T-cell transfer therapy).
• Monoclonal antibodies.
• Cancer vaccines.
• Immune system modulators.

Effectiveness: 

Immunotherapy has been shown to be an effective treatment for renal cancer with improved outcomes. For example, clinical trials of nivolumab with other treatments show better progression-free survival and overall response rates than traditional treatments. 

The response rates for immunotherapy in renal cancer vary between 20% and 40%, depending on the use of the specific drug and the stage of the tumor.

Side Effects: 

The common side effects of immunotherapy includes:

• Fatigue
• Rash and itchiness
• Diarrhoea
• Nausea and vomiting
• Decreased thyroid hormones

Future Directions: 

Emerging immunotherapies include combination therapies that combine checkpoint inhibitors with VEGF inhibitors or tyrosine kinase inhibitors. Researchers are exploring new immune-based therapies like bispecific T-cell engagers (BiTEs) and tumour vaccines, which have shown improved outcomes.

For example, Nivolumab (immunotherapy treatment) in combination with ipilimumab (targeted drug therapy) has shown effective survival rates as compared to sunitinib in advanced stages of renal cancer.

7.4.5 Chemotherapy

Chemotherapy is a common cancer treatment in which chemicals are used to destroy cancerous cells and prevent tumour growth. It uses cytotoxic drugs that kill rapidly dividing cancerous cells by interrupting their life cycle.

Doctors can treat chemotherapy alone or combine it with radiation therapy or surgery to achieve a better outcome. They usually administer chemotherapy medicines intravenously, but patients can also take them orally. It is an effective treatment but has many side effects.

Common Chemotherapy Regimens: 

Chemotherapy is more commonly used in transitional cell carcinoma (a rare type of kidney cancer). Gemcitabine and Cisplatin is a common drug that provides effective treatment against renal cancer.

Effectiveness: 

Success rates for chemotherapy in renal cancer are lower than other cancer treatments, such as targeted therapies or immunotherapies, due to their increased side effects. 

Side Effects: 

Chemotherapy targets all fast-growing cells including healthy and cancerous cells. These are common side effects of chemotherapy.

• Infection.
• Loss of appetite.
• Nausea and vomiting.
• Loss of appetite.
• Nausea and vomiting.
• Hair loss
• Neuropathy
• Anemia.
• Bleeding.

Combination with Other Treatments:

Chemotherapy has shown a positive impact in advanced stages of cancer with other treatments such as surgery, immunotherapy, or targeted therapy.

Studies have shown that chemotherapy alone is not highly effective for kidney cancer. Using it in combination with other treatments is more beneficial.

The NIH reported that chemotherapy regimens like gemcitabine and cisplatin show better results in treating transitional cell carcinoma, with response rates ranging from 40-60%.

7.5 Palliative Care

Palliative care is a supportive treatment method in which the patient with renal cancer is treated in other ways by managing pain and symptoms to improve the quality of life. This treatment method focuses on relieving severe pain, managing complicated symptoms, and addressing emotional and psychological concerns. 

Palliative care is an effective method to treat renal care patients. The common symptoms of renal cancer include pain, fatigue, decreased appetite, depressed mood, and anxiety. Palliative care is a supportive method to treat and manage these symptoms.

In palliative care, healthcare providers manage pain with medicines such as antibiotics, opioids, non-opioid analgesics, and nerve blocks. They also address fatigue through energy conservation techniques, ensure proper nutrition intake, and recommend physical activities.

The emotional and psychological aspects of kidney cancer are also managed through palliative care. It provides counselling services, support groups, and spiritual care to address anxiety, depression, and feelings of isolation in advanced stages of cancer.

The main goal of palliative care is to increase the quality of life for renal patients. The management of symptoms by improving daily living and enhancing nutritional support and physical functions helps to increase quality of life. 

Palliative care is effective with other treatment methods to manage the chronic condition of renal cancer. It is commonly combined with chemotherapy or surgical procedures to manage the side effects and symptoms of renal cancer.

The NIH featured that palliative care improves the quality of life in cancer patients. The kidney cancer patients treated with palliative care reported better management of symptom control with lower emotional distress and improved recovery outcomes.

7.6 Lifestyle and Supportive Measures

Balanced Diet: I

The American Oncology Institute highlighted the consumption of vegetables and fruits to live a healthy life. A balanced diet includes the consumption of fruits and vegetables because they contain vitamins, minerals, antioxidants, and anti-inflammatory properties to fight cancerous cells.

A balanced diet also maintains energy levels, supports the immune system, and promotes the healing process.

Specific Nutrients:

Foods that are high in specific nutrients such as fruits (berries, citrus fruits) and vegetables (green leafy) help manage oxidative stress because they enrich the body with antioxidants such as vitamins C and E.

Protein in the diet is also essential to build muscle growth, especially during treatment of renal cancer. Lean meats, fish, tofu, poultry and legumes contain high amounts of proteins that are recommended during treatment. 

Managing Side Effects: 

There are many side effects of cancer treatment. Nausea, vomiting, loss of appetite, and taste changes are more common. Dietary adjustments help manage these side effects better. Here are some common ways to manage these side effects.

Nausea is treated with small, frequent meals. Some anti-inflammatory foods such as ginger, also help to manage nausea. Avoiding greasy or strong-smelling foods also helps to manage this side effect. Doctors recommend nutrient-dense food to address loss of appetite. Foods rich in calories, like nut butter and protein shakes, can also help patients to maintain their weight.

Hydration: 

Hydration is important in the management of kidney disease. Proper fluid intake supports kidney function to flush out the toxins from the body. In chemotherapy, the patient is more at risk of dehydration due to exposure to chemicals. Adequate fluid intake also helps to relieve constipation and balance electrolytes.

Consultation with Dietitians: 

Every renal cancer patient has different nutritional requirements based on the stage of their cancer, treatment stages, and personal health issues.

Consultation with a registered dietitian helps to make customised nutrition plans according to the patient's specific needs. A dietitian helps develop a diet plan, monitor kidney function, and better manage symptoms. 

The American Cancer Society and the National Kidney Foundation highlighted the dietary guidelines for kidney cancer patient. It focuses on a nutrient-rich diet to boast the immune system and promotes kidney health. Kidney Cancer UK highlighted a balanced diet that comprises 

• One third fruits and vegetables
• About one third of carbohydrates
• One third combination of milk, dairy, meat, eggs, fish and small portions of foods high in sugar or fat.

7.6.2 Physical Activity

Exercise helps relieve cancer-related fatigue and depression and prevent muscle loss. It also helps people feel and sleep better, control weight, improve mental, heart, and brain health, and lower the risk of early death. 

The CDC advises that patients with chronic kidney disease should engage in at least 150 minutes of moderate-intensity aerobic exercise each week such as walking and yoga. Some muscle-strengthening activities, like weight training, should be recommended at least twice a week.

The safe exercise guidelines for renal patients include

• Start by walking at a slow or steady pace for 10 minutes at least 5 days a week
• After maintaining consistency, increase the exercise up to 20 minutes every other day in a brisk space. 
• Increase the time up to 30 minutes every other day after one month, 
• After 2 months, walk at least 30 minutes 5 times a week.

Safety Considerations for Renal Patients

These are some tips for renal patients  to ensure safer activity levels

• The rest days are essential for renal patients. The NKF recommended that renal patients should aim for three non-consecutive days a week.
• Don't exercise after eating or before going to bed. Also, avoid exercising if it's too humid and in hot weather conditions. 
• Before starting any activity, consult your nephrologist.
• Make sure to warm up before performing any activity to prevent injuries.
• If the renal patient is diabetic, monitor blood glucose levels on a routine basis.
• Avoid lifting heavy objects during exercise to prevent complications
• If the person has placed a catheter in the abdomen, avoid swimming. 
• After eating, wait for at least one hour to perform any exercise. 
• Stop exercising if the patient feels tired, nauseous, chest pain or irregular heartbeat.

For example

Studies have shown the positive effect of exercise in improving kidney health. According to research published in The Lancet Oncology, physical activity during cancer treatment shows a 37% reduction in cancer recurrence. Overall, exercise improves physical function and enhances long-term survival rates in renal patients.

7.6.3 Alternative Medicine

Alternative medicines play an important role in supporting overall kidney health. They help reduce symptoms to manage chronic renal failure. These medicines are used as complementary practices and should not be substituted for medically prescribed treatments.

Mind-body therapy (MBT) is an effective way to treat chronic kidney disease. It helps in the management of symptoms and improves overall well-being. It includes yoga, meditation, imagery and music therapies. 

Tai Chi involves gentle movement with great concentration and focus on breathing. It is known to improve circulation and reduce fatigue. The imagery technique involves imaging favourite scenes, pictures, or positive experiences to heal the body for faster recovery.

Yoga reduces stress, and anxiety and improves blood pressure and sugar levels. Some spiritual therapies are also involved in reducing depressive symptoms. 

The NIH also highlighted the role of Tai Chi training in improving renal and cardiac functions by reducing symptoms of anxiety and depression.

Biologically Based Practices: 

Some types of herbal supplements, vitamins, and dietary changes also help to improve kidney functions. Herbs like dandelion root are natural diuretics, and marshmallow root supports bladder health. Certain herbs, such as ginseng, interfere with kidney function, so it is advised to consult a doctor before using any herbs to prevent their adverse effects on kidney health. 

Manipulative and Body-Based Practices: 

The manipulative and body-based practices work on one or more parts to relieve pain, improve blood circulation and promote relaxation. It includes

• Massage therapies reduce stress and help better manage symptoms such as fatigue and discomfort during dialysis. 
• Secondary symptoms of renal failure, such as lower back pain and joint pain, can be addressed through chiropractic care due to the kidneys' proximity to the lower back region.
• Reflexology involves pressure points in the hands or feet to relieve pain from other parts of the body.

Biofield Therapy: 

Biofield therapy, often referred to as energy medicine, is based on the idea that the body possesses energy fields for the purpose of healing and promoting wellness. Doctors apply pressure on the body by positioning their hands within or around these fields. Some examples include:

Reiki: Reiki is the practice of balancing energy, either remotely or by touching or being close to the patient.

Therapeutic touch: Hands moving over the body's energy fields is known as therapeutic touch.

Whole Medical Systems: Traditional Chinese Medicine, Ayurveda.

Whole medical systems are beliefs and methods of healing that have developed over time in various cultures and regions of the world. Here are a few examples:

Ayurvedic medicine: An Indian technique that aims to cleanse the body and restore balance to the body, mind, and spirit. 

Traditional Chinese medicine: It is based on the belief that two forces in the body, must be balanced for one to stay healthy. Chinese medicine commonly uses acupuncture, which stimulates specific sites on the body to improve health, reduce symptoms of illness, and lower the side effects of medicines.

Homoeopathy: It requires a small amount of dose to trigger to automatically heal the body.

Naturopathic medicine: It involves herbal treatment that includes various methods to heal itself naturally. 

For example:

Several researches have shown that mind-body practices like yoga and meditation can enhance the quality of life for kidney patients by relieving anxiety, depression, and chronic pain. A study published in The Journal of Nephrology concluded that meditation reduces blood pressure in patients with chronic kidney disease (CKD).

 

8. Prevention

Kidney cancer is not always preventable but these are some ways which reduces the risk for developing kidney cancer. 

General Prevention Tips: 

These are some general prevention tips for renal cancer. 

• Quit smoking
• Maintaining a healthy body weight
• Control blood sugar and blood pressure levels.
• Avoid excessive use of NSAIDs such as ibuprofen and naproxen.
• Avoid exposure to certain toxins such as cadmium, asbestos, and trichloroethylene.
• Maintain a healthy lifestyle and eat a diet rich in fruits and vegetables.
• Be aware of certain risk factors that can’t be changed but can be followed up such as family history of kidney cancer and people born with von Hippel-Lindau disease.

Take Care of Your Kidneys: 

Maintaining kidney health through hydration and avoiding toxins.

The kidney's health is very important. You can follow these tips to take care of kidney health.

• Limit alcohol intake, as they can affect the kidneys and increase the risk of kidney cancer.
• Limit sodium and phosphorus intake in your diet as renal failure can increase the phosphorus levels in the blood.
• Ensure proper hydration and take 8 glasses of water daily.
• Limit protein-rich foods such as meat, eggs, fish and milk.

Awareness of Risk Factors:

These are some risk factors that increase the risk of renal cancer. 

• Smoking increases the risk of renal cell carcinoma
• Excess body weight
• High blood pressure
• Family history of renal cancer
• Workplace exposure to certain chemicals such as trichloroethylene or cadmium.
• Race and ethnicity, such as American Indian and Alaska Native people, are more at higher risk.
• Long-term use of painkillers such as acetaminophen
• People with advanced kidney disease such as dialysis
• Genetic and hereditary risk factors in people with diseases such as von Hippel-Lindau disease, hereditary papillary renal carcinoma, hereditary leiomyomatosis and renal cell cancer are more at higher risk.

Regular Check-ups: 

People who are at higher risk of renal cancer are recommended to undergo regular screening for early detection, which is linked with improved survival outcomes. CT scan, MRI scan and ultrasound scan can identify any changes in kidney cancer that help in early detection of disease and treatment. 

Genetic Counseling: 

Those who are at higher risk of developing renal cancer, such as family history or hereditary syndromes, require genetic counselling and testing. Genetic tests help to identify any gene mutations that cause inherited conditions.

Genetic tests involve predictive genetic testing that helps to identify the gene transferred from a parent that affects the risk of cancer.

The inherited gene diagnoses conditions like von Hippel-Lindau disease, hereditary leiomyomatosis, or Birt-Hogg-Dubé syndrome that are linked with an increased risk of developing renal cancer. 

For example: 

The American Cancer Society recommends maintaining a healthy weight, staying physically active, and avoiding smoking to reduce the risk of kidney cancer.

The NIH highlighted that quitting smoking alone reduces the risk of kidney cancer by 20-30% as compared to non-former smokers. 

9. Outlook / Prognosis

The prognosis of kidney cancer depends on the type and stage of kidney cancer. These steps are expected to help in the diagnosis of renal cancer.

Treatment Journey

The treatment depends on the health of the individual and the stage of renal cancer. Early-stage diagnosis has improved prognosis as compared to later stages. The majority of people with renal cancer are treated with surgery to remove tumours in the affected kidney. But it is not the only option.

It can also be treated with targeted therapy, immunotherapy, or radiation. Each stage requires consultation with a specialist to choose the best possible treatment method for better outcomes and improved quality of life. 

Recovery Process:

Post-recovery depends on the type of treatment the patient receives. A patient can expect a hospital stay after surgery followed by several weeks.

The side effects of each treatment are also required to be addressed accordingly.

Potential Complications:

The common side effects of each treatment includes fatigue, pain, or GIT issues. Immunotherapy and targeted treatments can also cause side effects such as skin rashes and high blood pressure.

Patients must strictly follow up to manage these symptoms and prevent recurrence.

Support Systems:

The support system includes family, friends and therapists that help to motivate the patient for better recovery.

They play an essential role in providing emotional support along with medical treatment and medicines. Palliative care is also helpful in managing these conditions. 

Long-term Outlook:

After surgery, renal patients are required to follow up with regular check-ups to monitor for any signs of recurrence. Survival rates can differ based on the stage of cancer at the time of diagnosis.

For example, early-stage kidney cancer (localised) boasts a 5-year survival rate of approximately 93%, whereas advanced cases have lower rates.

For Example:

According to the American Cancer Society, the 5-year survival rate are given as SEER (surveillance, epidemiology, and end results) stages.

SEER stages	5-year survival rate of renal cancer
Localized	93%
Regional	74%
Distant	17%
All combined SEER stages	78%

9.2 Is Kidney Cancer Curable?

The curability of kidney cancer depends on the stage of diagnosis and treatment methods.

 Early-Stage Curability: 

Kidney-stage treatment at early diagnosis is curable and has a higher success rate. Various treatment methods, including partial or radical nephrectomy, help treat renal cancer.

About 93% of cases show positive outcomes of renal cell carcinoma diagnosed at early stages in renal patients.

Advanced Stages: 

It is difficult to treat renal cancer in its advanced stages when cancer has spread to other parts of the body.

It is difficult to treat complex cases, but several treatment methods such as targeted therapy, immunotherapy, and innovative drug combinations, have shown positive results in increasing patient’s lives and managing symptoms and complications.

Factors Influencing Cure: 

These are some factors that depend on the curability of kidney disease.

• Stage at diagnosis: The early stage diagnosis of renal cancer show high durability as compared to later stage diagnosis
• Patient health: The patient's overall health is important to determine the curability of kidney cancer.
• Treatment efficacy: the response to treatment also depends on the curability of renal cancer.

Research and Advances: 

Many ongoing researchers are striving to improve the outcome of patients with kidney cancer. Advancements in various treatment methods, such as immunotherapy, targeted therapies and personalised medicines, ensure better treatment outcomes even in the later stages of kidney cancer.

Clinical trials also showed new strategies to increase the survival rate and improve the quality of life in renal patient. 

Patient Prognosis: 

The prognosis of each patient depends on the cancer stage, tumour size, response to treatment, and general health. A personalized treatment plan, along with meal plans, helps patients recover faster.

For example: 

According to the American Cancer Society, the 5-year survival rate for localised (stage 1) kidney cancer is 93%, while it's 14% for stage 4 kidney cancer. 

10. Living With Kidney Cancer

10.1 When Should I See My Healthcare Provider?

Living with kidney cancer requires careful monitoring, medical consultation and follow-up. These are some symptoms that require immediate medical attention to prevent further complications.

• Blood in the urine
• Feeling a lump near the kidney area
• Persistent fever and pain in the back
• Extreme weight loss

People who are at higher risk of developing kidney cancer require regular follow-up. Routine imaging tests such as ultrasounds, CT scans, and MRIs can identify any abnormalities of kidney structure and its functioning.

Healthcare providers usually recommend annual screening for patients who are at higher risk of renal cancer. 

The frequency of tests and screening depends on the symptoms and their complications. Renal patients, after treatment, are required to have follow-up appointments after 3 to 6 months.

After treatment of renal cancer, there are more chances of recurrence. If the patient observes these symptoms, they show reoccurrence, and the patient is required to seek immediate help from the doctor. 

• Fatigue and weight loss.
• Severe pain in the kidney area.
• Shortness of breath or other respiratory symptoms.

Emergency Situations

These are some emergency situations in which patients requires immediate medical intervention.

• Severe or sudden pain in kidney region (lower back or side).
• Unusual pain while urinating or complete urinary blockage.
• Severe blood in the urine or large clots.

The  NIH highlighted that patients with early diagnosis of renal cancer show a 90% improvement in 5-year survival rate.

10.2 What Questions Should I Ask My Healthcare Provider?

It is important to understand everything about a kidney cancer diagnosis to empower you and assist you in making informed choices regarding your treatment. Here are some questions to consider asking your healthcare provider:

1. What type and stage of kidney cancer do I have?
2. What are my treatment options, and what do you recommend?
3. How will treatment affect my daily life and activities?
4. What are the potential side effects of each treatment?
5. What is the expected prognosis with each treatment option?
6. Are there any clinical trials available for my condition?
7. How can I manage the side effects of treatment?
8. What lifestyle changes should I make during and after treatment?
9. What support services are available to me and my family?
10. How often will I need follow-up appointments and tests?