Renal Cell Carcinoma
Disease Details
Family Health Simplified
- Description
- Renal cell carcinoma is a type of kidney cancer that originates in the lining of the small tubes within the kidney.
- Type
- Renal cell carcinoma is a type of kidney cancer. It does not typically follow a straightforward pattern of genetic transmission, but certain hereditary conditions like von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell carcinoma (HLRCC), and hereditary papillary renal cell carcinoma (HPRCC) can increase the risk of developing this cancer. These hereditary conditions are usually inherited in an autosomal dominant fashion.
- Signs And Symptoms
- Historically, medical practitioners expected a person to present with three findings. This classic triad is 1: haematuria, which is when there is blood present in the urine, 2: flank pain, which is pain on the side of the body between the hip and ribs, and 3: an abdominal mass, similar to bloating but larger. It is now known that this classic triad of symptoms only occurs in 10–15% of cases, and is usually indicative that the renal cell carcinoma (RCC) is in an advanced stage. Today, RCC is often asymptomatic (meaning few to no symptoms) and is generally detected incidentally when a person is being examined for other ailments.Other signs and symptom may include haematuria; loin pain; abdominal mass; malaise, which is a general feeling of unwellness; weight loss and/or loss of appetite; anaemia resulting from depression of erythropoietin; erythrocytosis (increased production of red blood cells) due to increased erythropoietin secretion; varicocele, which is seen in males as an enlargement of the pampiniform plexus of veins draining the testis (more often the left testis) hypertension (high blood pressure) resulting from secretion of renin by the tumour; hypercalcemia, which is elevation of calcium levels in the blood; sleep disturbance or night sweats; recurrent fevers; and chronic fatigue.
- Prognosis
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The prognosis is influenced by several factors, including tumour size, degree of invasion and metastasis, histologic type, and nuclear grade. Staging is the most important factor in the outcome of renal cell cancer. The following numbers are based on patients first diagnosed in 2001 and 2002 by the National Cancer Data Base:
A Korean study estimated a disease-specific overall five-year survival rate of 85%. Taken as a whole, if the disease is limited to the kidney, only 20–30% develop metastatic disease after nephrectomy. More specific subsets show a five-year survival rate of around 90–95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80–85%. For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%. Factors as general health and fitness or the severity of their symptoms impact the survival rates. For instance, younger people (among 20–40 years old) have a better outcome despite having more symptoms at presentation, possibly due to lower rates spread of cancer to the lymph nodes (stage III).
Histological grade is related to the aggressiveness of the cancer, and it is classified in 4 grades, with 1 having the best prognosis (five-year survival over 89%), and 4 with the worst prognosis (46% of five-year survival).
Some people have the renal cell cancer detected before they have symptoms (incidentally) because of the CT scan (Computed Tomography Imaging) or ultrasound. Incidentally diagnosed renal cell cancer (no symptoms) differs in outlook from those diagnosed after presenting symptoms of renal cell carcinoma or metastasis. The five-year survival rate was higher for incidental than for symptomatic tumours: 85.3% versus 62.5%. Incidental lesions were significantly lower stage than those that cause symptoms, since 62.1% patients with incidental renal cell carcinoma were observed with Stage I lesions, against 23% were found with symptomatic renal cell carcinoma.If it has metastasized to the lymph nodes, the five-year survival is around 5% to 15%. For metastatic renal cell carcinoma, factors which may present a poor prognosis include a low Karnofsky performance-status score (a standard way of measuring functional impairment in patients with cancer), a low haemoglobin level, a high level of serum lactate dehydrogenase, and a high corrected level of serum calcium. For non-metastatic cases, the Leibovich scoring algorithm may be used to predict post-operative disease progression.Renal cell carcinoma is one of the cancers most strongly associated with paraneoplastic syndromes, most often due to ectopic hormone production by the tumour. The treatment for these complications of RCC is generally limited beyond treating the underlying cancer. - Onset
- The onset of renal cell carcinoma often occurs in individuals between the ages of 50 and 70. It typically lacks clear early symptoms, making it challenging to detect in its initial stages.
- Prevalence
- Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for approximately 85% of all kidney cancer cases. It is estimated that RCC affects about 1-2% of the population at some point in their lifetime. The incidence varies globally, with higher rates observed in North America and Europe. RCC is more common in men than in women, with a male-to-female ratio of around 2:1.
- Epidemiology
- The incidence of the disease varies according to geographic, demographic and, to a lesser extent, hereditary factors. There are some known risk factors, however the significance of other potential risk factors remains more controversial. The incidence of the cancer has been increasing in frequency worldwide at a rate of approximately 2–3% per decade until the last few years where the number of new cases has stabilised.The incidence of RCC varies between sexes, ages, races and geographic location around the world. Men have a higher incidence than women (approximately 1.6:1) and the vast majority are diagnosed after 65 years of age. Asians reportedly have a significantly lower incidence of RCC than whites and while African countries have the lowest reported incidences, African Americans have the highest incidence of the population in the United States. Developed countries have a higher incidence than developing countries, with the highest rates found in North America, Europe and Australia / New Zealand.
- Intractability
- Renal cell carcinoma (RCC) can be challenging to treat, especially in advanced stages. While early-stage RCC may be managed effectively with surgery, advanced or metastatic RCC often requires systemic therapies such as targeted therapy, immunotherapy, or combination treatments. These treatments aim to control the disease and improve survival, but a complete cure is uncommon for advanced cases, rendering it relatively intractable. However, ongoing research and new therapeutic approaches continue to improve outcomes for many patients.
- Disease Severity
- Renal cell carcinoma (RCC) severity can vary significantly based on the stage at diagnosis. Early-stage RCC (localized to the kidney) often has a better prognosis and may be effectively treated with surgery. Advanced stages (spread beyond the kidney) typically have a poorer prognosis and may require additional treatments like targeted therapy, immunotherapy, or chemotherapy. Early detection is crucial for improving outcomes.
- Healthcare Professionals
- Disease Ontology ID - DOID:4450
- Pathophysiology
- The tumour arises from the cells of the proximal renal tubular epithelium. It is considered an adenocarcinoma. There are two subtypes: sporadic (that is, non-hereditary) and hereditary. Both such subtypes are associated with mutations in the short-arm of chromosome 3, with the implicated genes being either tumour suppressor genes (VHL and TSC) or oncogenes (like c-Met).
- Carrier Status
- Renal cell carcinoma (RCC) primarily arises sporadically with no clear carrier status. However, certain hereditary conditions, such as von Hippel-Lindau (VHL) syndrome, can increase the risk of developing RCC. In such cases, individuals may carry mutations in the VHL gene.
- Mechanism
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Renal cell carcinoma (RCC) is a type of kidney cancer that originates in the lining of the proximal convoluted tubule. The mechanisms behind RCC involve several molecular pathways:
**Mechanism:**
1. **Genetic Mutations:** Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene are a hallmark of clear cell RCC, the most common subtype of RCC.
2. **Dysregulation of Hypoxia-Inducible Factors (HIFs):** Loss of VHL function leads to the stabilization of HIFs, which are normally degraded under normal oxygen conditions. Stabilized HIFs can activate a variety of genes that promote angiogenesis, cell growth, and survival.
3. **Angiogenesis:** The activation of HIFs leads to increased expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which promote the formation of blood vessels to supply the growing tumor.
4. **Cell Proliferation and Survival:** HIFs also enhance the expression of genes involved in cell cycle regulation, glucose metabolism, and apoptosis inhibition, promoting neoplastic cell growth and survival under hypoxic conditions.
**Molecular Mechanisms:**
1. **VHL-HIF Pathway:** Inactivation of the VHL gene results in the accumulation of HIF transcription factors, particularly HIF-1α and HIF-2α. These factors drive the expression of genes that support tumor growth through enhanced angiogenesis and metabolic adaptation.
2. **PI3K/AKT/mTOR Pathway:** This signaling pathway is often overactive in RCC due to mutations or dysregulation, leading to increased cell growth and survival.
3. **Epigenetic Changes:** Alterations in DNA methylation and histone modification can silence tumor suppressor genes or activate oncogenes, contributing to RCC progression.
4. **Chromatin Remodeling Complexes:** Mutations in genes encoding components of chromatin remodeling complexes, such as PBRM1, SETD2, and BAP1, are frequently observed in RCC and can influence gene expression and tumor behavior.
5. **MET and c-Met Pathway:** Alterations in the MET gene, which encodes the hepatocyte growth factor receptor (HGFR), can lead to increased cell proliferation and metastasis.
These molecular mechanisms collectively contribute to the pathogenesis and progression of renal cell carcinoma, guiding current therapeutic approaches and ongoing research into targeted treatments. - Treatment
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Renal cell carcinoma (RCC) treatment options typically include:
1. **Surgery**:
- Partial nephrectomy (removal of the tumor and a small margin of healthy tissue)
- Radical nephrectomy (removal of the entire kidney, sometimes along with surrounding tissue and lymph nodes)
2. **Ablation**:
- Cryoablation (freezing cancer cells)
- Radiofrequency ablation (heating cancer cells)
3. **Targeted Therapy**:
- Medications that target specific pathways or genes involved in cancer growth (e.g., tyrosine kinase inhibitors like sunitinib and pazopanib)
4. **Immunotherapy**:
- Immune checkpoint inhibitors (e.g., nivolumab, ipilimumab)
5. **Radiation Therapy**:
- Generally used for palliation in metastatic cases rather than as a primary treatment for localized tumors
6. **Active Surveillance**:
- Monitoring small or slow-growing RCC with regular imaging and check-ups
7. **Clinical Trials**:
- Participation in studies of new treatments
Treatment plans are personalized based on the stage of cancer, location, patient health, and other factors. - Compassionate Use Treatment
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For renal cell carcinoma (RCC), compassionate use treatment, off-label, or experimental treatments can include several options:
1. **Checkpoint Inhibitors**: Drugs like nivolumab (Opdivo) are FDA approved for RCC but may be used compassionately in various stages or specific patient populations not covered by the standard indications.
2. **Targeted Therapies**: Examples like cabozantinib (Cabometyx) or lenvatinib (Lenvima) can be considered for off-label use depending on the patient's tumor profile and previous treatments.
3. **Combination Therapies**: Experimental protocols combining nivolumab with ipilimumab (Yervoy) or combining immunotherapies with targeted agents are under investigation.
4. **Clinical Trials**: Participation in clinical trials can offer access to cutting-edge therapies, including new immunotherapies, targeted agents, and combination approaches.
5. **Adoptive Cell Therapy**: Techniques such as CAR-T cell therapy, though primarily experimental and more commonly associated with hematologic cancers, are being explored for RCC.
Compassionate use is typically considered when standard treatments are no longer effective, and the patient is not eligible for clinical trials. Always consult with a medical professional to evaluate the best course of action based on the individual health condition and treatment history. - Lifestyle Recommendations
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Lifestyle recommendations for renal cell carcinoma include:
1. **Healthy Diet**: Focus on a diet rich in fruits, vegetables, whole grains, and lean proteins. Reducing the intake of processed foods and saturated fats can also be beneficial.
2. **Regular Exercise**: Engage in regular physical activity to maintain a healthy weight and improve overall wellbeing. Aim for at least 150 minutes of moderate exercise per week.
3. **Avoid Tobacco**: Stopping smoking is crucial, as tobacco use is a significant risk factor for kidney cancer.
4. **Limit Alcohol**: Moderation is key; excessive alcohol intake can contribute to an increased risk of various cancers.
5. **Stay Hydrated**: Drink adequate amounts of water daily to maintain kidney health.
6. **Monitor Blood Pressure**: High blood pressure is a risk factor; manage it through lifestyle changes and medications if needed.
7. **Regular Check-ups**: Attend regular medical check-ups to monitor kidney function and overall health, especially if you have a family history of kidney cancer.
8. **Avoid Exposure to Toxins**: Limit exposure to harmful chemicals and toxins that can increase cancer risk, such as certain herbicides and industrial solvents.
Implementing these lifestyle changes can help improve overall health and potentially reduce the risk of disease progression or recurrence. - Medication
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Renal cell carcinoma (RCC) is a type of kidney cancer. Treatment options include surgery as a primary approach, but various medications are also used. Here are some categories and examples of medications for RCC:
1. **Targeted Therapy:**
- **Sunitinib** (Sutent)
- **Sorafenib** (Nexavar)
- **Pazopanib** (Votrient)
- **Axitinib** (Inlyta)
- **Cabozantinib** (Cabometyx)
- **Lenvatinib** (Lenvima)
2. **Immunotherapy:**
- **Nivolumab** (Opdivo)
- **Pembrolizumab** (Keytruda)
- **Atezolizumab** (Tecentriq)
- **Ipilimumab** (Yervoy)
3. **mTOR Inhibitors:**
- **Temsirolimus** (Torisel)
- **Everolimus** (Afinitor)
4. **Cytokines:**
- **Interleukin-2 (IL-2)**
These treatments can be used alone or in combination, depending on the specific case and patient health factors. - Repurposable Drugs
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Repurposable drugs for renal cell carcinoma (RCC) include:
1. Metformin: Commonly used for type 2 diabetes, metformin has shown potential anti-cancer properties.
2. Thalidomide: Originally developed as a sedative, it has anti-angiogenic properties that may inhibit the growth of RCC.
3. Statins: Typically used to lower cholesterol, they may have anti-cancer effects by inhibiting cell proliferation and inducing apoptosis.
4. Aspirin: Known for its anti-inflammatory properties, it may reduce cancer progression through COX-2 inhibition.
This list is based on emerging research, and clinical trials are necessary to confirm efficacy and safety in RCC treatment. Always consult healthcare providers for medical advice regarding treatment options. - Metabolites
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For renal cell carcinoma (RCC), key metabolites include:
1. **Sarcosine**: Increased levels have been associated with RCC.
2. **Lactate**: Elevated in cancer cells due to the Warburg effect.
3. **Glutamine**: Altered glutamine metabolism is observed in RCC.
4. **Fumarate and Succinate**: Accumulation due to mutations in fumarate hydratase (FH) and succinate dehydrogenase (SDH) respectively.
5. **Glucose**: Altered glucose metabolism is a hallmark of many cancers, including RCC.
6. **Lipid Metabolites**: Changes in fatty acid metabolism are often seen in RCC.
These metabolites can play roles in cancer growth, progression, and serve as potential biomarkers for RCC diagnosis and prognosis. - Nutraceuticals
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In the context of renal cell carcinoma, nutraceuticals refer to food-derived products that have potential therapeutic benefits. Research into the effectiveness of nutraceuticals for renal cell carcinoma is ongoing, but some commonly studied compounds include curcumin, green tea extract (EGCG), resveratrol, and omega-3 fatty acids. These compounds are thought to have anti-inflammatory and antioxidant properties that may support conventional cancer treatments, though robust clinical evidence is still needed to confirm their efficacy.
No notable interactions (nan) or contraindications are specifically highlighted in the provided context; however, it is always advisable to consult with a healthcare provider before starting any new supplement regimen. - Peptides
- Regarding renal cell carcinoma (RCC), peptides are being investigated for their potential in diagnosis and treatment. Peptide-based vaccines and targeted therapies utilizing peptides that bind specifically to tumor-associated antigens are areas of active research. These exploratory treatments aim to enhance the immune response against cancer cells and improve patient outcomes.