Kidney Cancer (Renal Cell Carcinoma)

What is Kidney Cancer?

Kidney cancer develops when cells in the kidney grow abnormally and form a tumor. The kidneys are two bean-shaped organs located on either side of the spine, just below the rib cage. They filter waste from blood, produce urine, regulate blood pressure, and maintain electrolyte balance.

Renal Cell Carcinoma (RCC)

About 90% of kidney cancers are renal cell carcinoma, which originates in the lining of the kidney's tubules (the tiny tubes that filter blood and create urine). RCC is the most common kidney cancer in adults.

Incidental Discovery

About 50-60% of kidney cancers are now discovered incidentally on CT scans or ultrasounds performed for unrelated reasons. This has led to earlier detection and improved outcomes, but also raises questions about which small tumors need immediate treatment.

Types of Kidney Cancer

Renal Cell Carcinoma (RCC) - 90%

RCC has several subtypes based on how cells appear under a microscope:

Clear Cell RCC (70-75%)

• Most common type of kidney cancer
• Appearance: Cells look clear or pale under microscope due to lipid and glycogen content
• VHL gene: Often associated with mutations in the VHL (Von Hippel-Lindau) gene
• Growth pattern: Can be slow-growing or aggressive
• Treatment response: Best response to targeted therapies (VEGF inhibitors, mTOR inhibitors) and immunotherapy

Papillary RCC (10-15%)

• Second most common
• Types: Type 1 (better prognosis) and Type 2 (more aggressive)
• Appearance: Finger-like projections when viewed microscopically
• Characteristics: More common in people with hereditary papillary RCC or with multiple tumors
• Treatment: Surgery primary; less responsive to standard targeted therapies than clear cell

Chromophobe RCC (5%)

• Arises from different kidney cell type
• Prognosis: Generally better than clear cell; less likely to spread
• Association: Can occur in Birt-Hogg-Dubé syndrome
• Treatment: Surgery is primary treatment

Rare RCC Subtypes

• Collecting duct carcinoma (<1%): Aggressive, poor prognosis
• Medullary carcinoma (<1%): Very aggressive, associated with sickle cell trait
• Translocation RCC: More common in children and young adults
• Unclassified RCC (4-5%): Doesn't fit other categories

Other Kidney Cancers (10%)

Transitional Cell Carcinoma (5-10%)

• Also called urothelial carcinoma
• Begins in the renal pelvis (where urine collects before going to bladder)
• Similar to bladder cancer in cells and treatment
• Associated with smoking

Wilms Tumor (Nephroblastoma)

• Most common kidney cancer in children
• Peak age: 3-4 years old
• Very responsive to treatment; cure rate >90%
• Treated with surgery, chemotherapy, sometimes radiation

Renal Sarcoma (<1%)

• Rare tumors of connective tissue, blood vessels, or smooth muscle
• Aggressive behavior
• Treatment similar to soft tissue sarcomas

Symptoms and Warning Signs

Early kidney cancer often causes no symptoms. When symptoms occur, the cancer may be advanced.

Classic Triad (Only 10% of Patients)

• Hematuria (blood in urine): Urine appears pink, red, or cola-colored
• Flank pain: Persistent pain in the side or back, below the ribs
• Palpable abdominal mass: Lump or swelling in the abdomen or side

When all three symptoms occur together, the cancer is usually advanced.

Common Symptoms

• Hematuria (40-50%): May be intermittent; sometimes visible only under microscope
• Flank or back pain (40%): Usually dull, persistent ache
• Unexplained weight loss (30%): Without trying
• Fatigue (20-30%): Persistent tiredness
• Fever (20%): Not due to infection, comes and goes
• Night sweats: Drenching sweats
• Loss of appetite
• Anemia: Low red blood cells causing weakness and pallor

Paraneoplastic Syndromes (20-30%)

Kidney cancer can cause symptoms unrelated to the tumor itself by producing hormones or proteins:

• High blood pressure: From excess renin production
• High calcium (hypercalcemia): Causes fatigue, confusion, constipation, bone pain
• Polycythemia (high red blood cells): From excess erythropoietin
• Liver dysfunction (Stauffer syndrome): Abnormal liver tests without liver metastases

Symptoms of Metastatic Disease

If kidney cancer has spread:

• Bone pain: If spread to bones (30-40% of metastatic cases)
• Cough, shortness of breath, coughing blood: If spread to lungs (most common site, 50-60%)
• Headaches, seizures, neurological symptoms: If spread to brain (5-10%)
• Jaundice, abdominal swelling: If spread to liver

Causes and Risk Factors

The exact cause of most kidney cancers is unknown, but several risk factors have been identified:

Lifestyle Risk Factors

Smoking (Strongest Modifiable Risk Factor)

• Increases risk by 50-100%
• Risk proportional to amount smoked and duration
• Risk decreases after quitting but takes 10-15 years to return to baseline
• Accounts for about 30% of kidney cancers in men, 25% in women

Obesity

• Increases risk by 20-30% for every 5-unit increase in BMI
• Mechanism: Hormonal changes, inflammation
• Stronger association in women than men
• Weight loss may reduce risk

High Blood Pressure (Hypertension)

• Increases risk by 20-60%
• Unclear if hypertension itself or medications cause increased risk
• May be related to kidney damage from chronic high blood pressure

Medical Conditions

Chronic Kidney Disease

• Patients on long-term dialysis have increased risk
• Acquired cystic kidney disease develops in 80-90% of dialysis patients after 10 years
• Annual screening recommended for dialysis patients

Von Hippel-Lindau (VHL) Disease

• Hereditary syndrome with high kidney cancer risk (40-70% lifetime risk)
• Caused by mutation in VHL tumor suppressor gene
• Multiple, bilateral kidney tumors common
• Regular screening recommended starting age 15-16
• Also causes brain/spinal tumors, eye tumors, pheochromocytomas

Other Hereditary Syndromes

• Hereditary papillary RCC: Multiple papillary type 1 tumors
• Birt-Hogg-Dubé syndrome: Chromophobe and hybrid tumors
• Hereditary leiomyomatosis RCC: Aggressive papillary type 2 tumors
• Tuberous sclerosis: Benign angiomyolipomas and occasionally RCC

Demographic Factors

• Age: Risk increases with age; peak incidence 60-70 years
• Gender: Men 2× more likely than women
• Race: Higher incidence in African Americans and American Indians

Occupational and Environmental

• Trichloroethylene (TCE): Industrial solvent; possible link
• Asbestos exposure
• Cadmium exposure
• Organic solvents

Medications

• Phenacetin-containing analgesics: Now banned in most countries
• Some blood pressure medications: Conflicting evidence; may be confounded by hypertension itself

Protective Factors

• Moderate alcohol consumption: May slightly reduce risk (unclear mechanism)
• Physical activity: Some evidence for protective effect

Diagnosis and Screening

Screening

No routine screening recommended for average-risk individuals. However, high-risk groups may benefit:

Who Should Consider Screening?

• Von Hippel-Lindau disease: Annual MRI or CT starting age 15-16
• Other hereditary syndromes: Per syndrome-specific guidelines
• Long-term dialysis patients: Annual ultrasound or CT
• Strong family history: Discuss with doctor

Diagnostic Tests

Imaging Studies

CT Scan with Contrast (Gold Standard)

• Most accurate test for detecting and characterizing kidney masses
• Triple-phase protocol: Images before contrast, during arterial phase, and delayed phase
• Can determine: Size, location, enhancement pattern, involvement of nearby structures
• Also evaluates: Renal vein, inferior vena cava, lymph nodes, adrenal glands
• Limitation: Contrast may not be safe if kidney function is poor

MRI

• Alternative to CT when CT contrast contraindicated
• Excellent for: Evaluating tumor thrombus in renal vein/IVC
• No radiation exposure
• Good for characterizing cystic lesions

Ultrasound

• Often first test if kidney mass suspected
• Can differentiate: Solid masses from simple cysts
• Limitations: Less detailed than CT/MRI; operator-dependent
• Used for screening in high-risk populations

Chest Imaging

• Chest X-ray or CT: To check for lung metastases
• Routine for all kidney cancer diagnoses

Bone Scan or Brain MRI

• Not routine
• Ordered if: Symptoms suggest metastases, elevated alkaline phosphatase, or high-risk features

Laboratory Tests

• Urinalysis: Check for blood (microscopic or visible)
• Complete blood count (CBC): Anemia or polycythemia
• Comprehensive metabolic panel: Kidney function (creatinine), liver function, calcium
• Lactate dehydrogenase (LDH): Prognostic marker

Biopsy

Usually NOT needed before surgery if imaging clearly shows kidney cancer. However, biopsy may be considered for:

• Small tumors under active surveillance: To confirm cancer vs. benign
• Metastatic disease: Before starting systemic therapy
• Uncertain diagnosis: If imaging unclear (infection, lymphoma, metastasis from other cancer)
• Planning ablation: For patients who aren't surgical candidates

Biopsy limitations: 10-20% non-diagnostic rate, small risk of bleeding or seeding tumor along needle tract.

Bosniak Classification (For Cystic Lesions)

CT/MRI findings of kidney cysts are classified to guide management:

• Bosniak I: Simple benign cyst - no follow-up needed
• Bosniak II: Minimally complex cyst - benign, no follow-up needed
• Bosniak IIF: Complex cyst requiring follow-up - 5% cancer risk
• Bosniak III: Indeterminate cystic mass - 50% cancer risk, surgery often recommended
• Bosniak IV: Clearly malignant cystic mass - 90% cancer risk, requires treatment

Staging

Kidney cancer is staged using the TNM system (Tumor, Node, Metastasis):

Tumor (T) Classification

• T1a: ≤4 cm, limited to kidney
• T1b: >4 cm but ≤7 cm, limited to kidney
• T2a: >7 cm but ≤10 cm, limited to kidney
• T2b: >10 cm, limited to kidney
• T3a: Extends into renal vein, perirenal fat, or renal sinus fat
• T3b: Extends into vena cava below diaphragm
• T3c: Extends into vena cava above diaphragm or invades vena cava wall
• T4: Invades beyond Gerota's fascia (including adrenal gland on same side)

Lymph Nodes (N)

• N0: No lymph node involvement
• N1: Metastases in regional lymph nodes

Metastasis (M)

• M0: No distant metastases
• M1: Distant metastases present

Nuclear Grade (Fuhrman or WHO/ISUP)

Describes how abnormal cells look under microscope:

• Grade 1: Well-differentiated (best prognosis)
• Grade 2: Moderately differentiated
• Grade 3: Poorly differentiated
• Grade 4: Undifferentiated (worst prognosis)

Treatment Options

Treatment depends on stage, tumor size, patient health, and kidney function.

Surgery (Primary Treatment for Localized Disease)

Partial Nephrectomy (Nephron-Sparing Surgery)

Preferred for T1 tumors (≤7 cm) when technically feasible:

• Procedure: Remove tumor with margin of healthy tissue, preserve rest of kidney
• Advantages: Preserves kidney function, lower risk of chronic kidney disease, same cancer control as radical nephrectomy for T1 tumors
• Approaches: Open surgery, laparoscopic, or robotic-assisted
• Ideal for: Single kidney, bilateral tumors, poor kidney function, hereditary syndromes
• Cancer control: Equivalent to radical nephrectomy for appropriately selected tumors

Radical Nephrectomy

Removal of entire kidney, adrenal gland, and surrounding fatty tissue:

• Indications: T2 tumors (>7 cm), centrally located tumors not amenable to partial nephrectomy, T3/T4 tumors
• Approaches: Open (most common for large/complex tumors), laparoscopic, robotic
• Recovery: Hospital stay 2-7 days depending on approach
• Prognosis: Most patients function well with one kidney (50% function is adequate)

Lymph Node Dissection

• Not routine if lymph nodes appear normal on imaging
• Performed if: Enlarged nodes suspicious for metastases
• Therapeutic benefit unclear but provides staging information

Cytoreductive Nephrectomy (Metastatic Disease)

• Removing primary tumor even when metastases present
• Previously routine before immunotherapy (interferon era)
• Current approach: More selective; consider if:
  • Good performance status
  • Limited metastatic burden
  • Symptoms from primary tumor
  • After initial systemic therapy response
• Deferred in: Poor performance status, extensive metastases, sarcomatoid histology

Metastasectomy

• Surgical removal of metastases in select patients
• Consider if: Limited number of metastases (oligometastatic), disease-free interval >1 year, complete resection possible
• Sites: Lung (most common), brain, bone, adrenal
• Can improve survival in carefully selected patients

Active Surveillance

Monitoring small kidney tumors without immediate treatment:

• Candidates: Small tumors (≤4 cm, especially <2 cm), elderly patients, significant comorbidities, limited life expectancy
• Rationale: Many small renal masses grow slowly; 20-30% are benign; risks of treatment may outweigh benefits in select patients
• Protocol: Initial imaging every 3-6 months, then annually if stable
• Intervention if: Rapid growth (>0.5 cm/year), development of symptoms, patient preference changes
• Outcomes: Cancer-specific survival >95% with delayed intervention if needed

Ablative Therapies

For patients who are poor surgical candidates or prefer less invasive options:

Cryoablation

• Freeze tumor using argon gas probes inserted through skin (percutaneous) or during laparoscopy
• Best for: Posterior or lateral tumors <3-4 cm
• Outpatient or short hospital stay
• Efficacy: 90-95% for tumors <3 cm

Radiofrequency Ablation (RFA)

• Heat tumor using radio waves
• Similar indications to cryoablation
• Slightly lower efficacy than cryoablation for kidney tumors

Limitations of Ablation

• Higher local recurrence rates than surgery (5-10% vs <5%)
• No pathology specimen obtained
• Best for small (<3 cm), exophytic (growing outward) tumors
• Requires lifelong imaging surveillance

Systemic Therapy (Metastatic Disease)

Major advances in the last 15 years have transformed treatment of metastatic RCC.

Immunotherapy

Checkpoint inhibitors help immune system recognize and attack cancer:

First-Line Combinations (Current Standard)

• Nivolumab (Opdivo) + Ipilimumab (Yervoy):
  • Dual checkpoint inhibition (PD-1 + CTLA-4)
  • Superior overall survival vs. sunitinib
  • Best for intermediate/poor risk patients
  • Response rates: 40%
• Pembrolizumab (Keytruda) + Axitinib (Inlyta):
  • Checkpoint inhibitor + VEGF inhibitor
  • Improved progression-free and overall survival vs. sunitinib
  • For all risk groups
• Nivolumab + Cabozantinib:
  • Checkpoint inhibitor + tyrosine kinase inhibitor
  • Superior progression-free survival

Side Effects of Immunotherapy

• Immune-related adverse events (irAEs): Immune system attacks normal tissues
• Common: Rash, diarrhea/colitis, thyroid dysfunction, liver inflammation
• Serious but rare: Pneumonitis, myocarditis, neurological effects
• Management: Corticosteroids for moderate-severe irAEs

Targeted Therapy

VEGF Inhibitors (Tyrosine Kinase Inhibitors)

Block blood vessel growth that feeds tumors:

• Sunitinib (Sutent): Previous standard first-line; 4 weeks on, 2 weeks off
• Pazopanib (Votrient): Continuous daily dosing; similar efficacy to sunitinib
• Cabozantinib (Cabometyx): Now used in combination or second-line
• Axitinib (Inlyta): Used in combination with immunotherapy
• Lenvatinib (Lenvima) + Everolimus: Second-line option

Common Side Effects of TKIs

• Fatigue
• Diarrhea
• Hypertension (high blood pressure)
• Hand-foot syndrome (palmar-plantar erythrodysesthesia)
• Hypothyroidism
• Loss of appetite, nausea

mTOR Inhibitors

• Everolimus (Afinitor): Second-line after VEGF inhibitor failure
• Temsirolimus (Torisel): First-line for poor-risk patients (less commonly used now)

Bevacizumab (Avastin) + Interferon

• Older regimen, rarely used now
• Monoclonal antibody against VEGF

Treatment Selection

Risk stratification using IMDC (International Metastatic RCC Database Consortium) criteria helps guide therapy:

IMDC Risk Factors (Unfavorable)

• KPS <80% (performance status)
• Time from diagnosis to treatment <1 year
• Hemoglobin < lower limit of normal
• Calcium > upper limit of normal
• Neutrophils > upper limit of normal
• Platelets > upper limit of normal

Risk Groups

• Favorable (0 factors): Median survival 43 months
• Intermediate (1-2 factors): Median survival 23 months
• Poor (3-6 factors): Median survival 8 months

Radiation Therapy

• Not used for primary kidney cancer (RCC is radioresistant)
• Palliative treatment for:
  • Bone metastases (pain control, prevent fractures)
  • Brain metastases
  • Spinal cord compression
• Stereotactic radiosurgery (SRS): Focused radiation for brain or spine metastases

Chemotherapy

• Generally ineffective for RCC
• RCC is chemoresistant due to multi-drug resistance genes
• Exceptions: Collecting duct and medullary carcinomas may respond to platinum-based chemotherapy

Prognosis and Survival

Survival by Stage

• Localized (Stage I-II): 93% and 83% 5-year survival respectively
• Regional (Stage III): 70% 5-year survival
• Distant metastases (Stage IV): 15% 5-year survival
• Overall (all stages): 77% 5-year survival

Prognostic Factors

Favorable Factors

• Early stage (I-II)
• Small tumor size
• Low nuclear grade (1-2)
• Clear cell histology (paradoxically better for metastatic disease due to treatment response)
• No sarcomatoid features
• Good performance status
• Normal calcium, hemoglobin

Unfavorable Factors

• Advanced stage (III-IV)
• High nuclear grade (3-4)
• Sarcomatoid or rhabdoid features (20-30% worse survival)
• Tumor necrosis
• Microvascular invasion
• Collecting duct or medullary histology
• Poor performance status
• Hypercalcemia, anemia, thrombocytosis, elevated LDH

Recurrence Risk

• Overall recurrence after surgery: 20-30%
• Higher risk: Stage III (30-50%), high grade, tumor size >7 cm
• Lower risk: Stage I (<10%), low grade, tumor size <4 cm
• Timing: Most recurrences within 2-3 years, but can occur 10+ years later
• Common sites: Lungs (most common), bones, lymph nodes, liver, brain, contralateral kidney

Surveillance After Surgery

Regular imaging to detect recurrence early:

Low Risk (Stage I, low grade)

• CT or MRI abdomen/pelvis at 6 months, then annually for 5 years
• Chest imaging (X-ray or low-dose CT) annually

Intermediate/High Risk (Stage II-III, high grade)

• CT chest/abdomen/pelvis every 3-6 months for 3 years, then annually to year 5
• May continue beyond 5 years given late recurrence potential

Prevention

While kidney cancer cannot be completely prevented, you can reduce your risk:

Modifiable Risk Factors

1. Don't Smoke (Most Important)

• If you smoke, quit - risk decreases over time after quitting
• Avoid secondhand smoke exposure
• Smoking cessation programs, nicotine replacement, medications (varenicline, bupropion) can help

2. Maintain Healthy Weight

• Achieve and maintain BMI in healthy range (18.5-24.9)
• Weight loss if overweight/obese
• Even modest weight loss can reduce risk

3. Control Blood Pressure

• Regular blood pressure monitoring
• Lifestyle modifications: diet, exercise, limit sodium, limit alcohol
• Medications as prescribed by doctor
• Target: <130/80 mmHg for most people

4. Stay Physically Active

• Regular exercise may reduce risk
• Aim for 150+ minutes moderate aerobic activity per week
• Also helps with weight management and blood pressure control

5. Limit Occupational Exposures

• Follow workplace safety guidelines for chemical exposures
• Use protective equipment
• Industries to be aware of: metalworking, petroleum products, printing

For High-Risk Individuals

Hereditary Syndromes

• Genetic counseling and testing if strong family history
• Regular screening: MRI or CT starting in teens/early 20s for VHL disease and other syndromes
• Prophylactic surgery: Generally not recommended; surveillance preferred

Dialysis Patients

• Annual screening with ultrasound or CT
• Discuss with nephrologist

Diet

• No specific foods proven to prevent kidney cancer
• Overall healthy diet: Fruits, vegetables, whole grains, lean protein
• Limit processed and red meat
• Stay hydrated
• Moderate alcohol: May have slight protective effect but balance with other health risks

Living with Kidney Cancer

After Surgery

Living with One Kidney

• Most people function normally with one kidney (50% function is adequate)
• Protect remaining kidney:
  • Stay hydrated (8-10 cups water daily)
  • Control blood pressure and diabetes
  • Avoid nephrotoxic medications (NSAIDs, certain antibiotics) when possible
  • Regular kidney function monitoring (creatinine, GFR)
• Exercise: Safe and encouraged; use common sense to protect kidney (avoid contact sports with high injury risk)
• Diet: No major restrictions unless kidney function declines

Chronic Kidney Disease

• Some patients develop reduced kidney function after surgery
• More common after radical nephrectomy than partial
• Regular monitoring and management by nephrologist if needed

Managing Treatment Side Effects

• Immunotherapy side effects: Report any new symptoms promptly; irAEs often manageable if caught early
• Targeted therapy: See fatigue and diarrhea management pages
• Hand-foot syndrome: Moisturizing creams, avoid pressure/friction, dose reduction if severe
• Hypertension: Blood pressure medications, monitoring

Emotional Support

• Anxiety and depression common with cancer diagnosis
• Support groups (in-person or online)
• Counseling or therapy
• Communicate openly with family and healthcare team

Support Resources

• Kidney Cancer Association: kidneycancer.org
• American Cancer Society: cancer.org
• CancerCare: cancercare.org
• National Cancer Institute: cancer.gov

Frequently Asked Questions