Renal Cell Carcinoma

Overview

Renal cell carcinoma (RCC) is a malignancy arising from the proximal convoluted tubules of the kidney. The most common histological subtype is clear cell carcinoma, which is named based on its appearance.

RCC most commonly metastasises to the lungs, but can also spread to the liver, bone, adrenal glands, spleen, pancreas, colon, and regional lymph nodes.

Wilms’ tumour (nephroblastoma) is a type of renal cancer seen in children <5 years old.

Most RCCs are sporadic, however, they are associated with some genetic syndromes such as von Hippel-Lindau syndrome.

Epidemiology

• Over 10,000 new renal cancers are diagnosed yearly in the UK
• It is seen in both sexes, but 60% of new diagnoses are in men
• Incidence is highest in people aged 55-75 years old
• Renal cancer is the 7^th most common cancer in the UK

Risk Factors

• Smoking – one of the most well-established risk factors for RCC
• Male sex
• >55 years old
• Obesity
• Hypertension
• Family history
• Hereditary syndromes – such as von Hippel-Lindau syndrome
• Polycystic kidney disease – the risk is thought to be slightly increased

Presentation

Overview

More than 50% of RCCs are asymptomatic and diagnosed incidentally during imaging for other issues. Features of RCC may include:

• A classic triad of symptoms:
  • The whole triad is rare and only seen in <10% of people, but each feature may still present on its own:
    • Haematuria
    • Flank pain
    • Abdominal mass
• Constitutional symptoms – fever, unexplained weight loss, night sweats (up to 20%):
  • May suggest metastatic disease
• Non-reducing or isolated right-sided varicocele:
  • Due to the tumour compressing the testicular veins
  • Isolated right-sided varicoceles are rare due to differences in testicular venous drainage between the right and left sides, therefore, their presence can suggest malignancy
• Bilateral lower limb oedema:
  • Due to compression of the inferior vena cava
• Paraneoplastic features (up to 30%):
  • Endocrine:
    • Erythropoietin secretion leading to polycythaemia
    • Parathyroid hormone-related protein secretion leading to hypercalcaemia
    • Adrenocorticotrophic hormone secretion leading to Cushing’s syndrome
  • Liver dysfunction:
    • Due to liver metastases
    • Stauffer syndrome – cholestatic liver function tests with or without hepatosplenomegaly in the absence of metastases:
      • Its pathogenesis is not entirely understood but is thought to be due to the release of interleukin 6 (IL-6) from cancerous cells
  • Myopathy

Referral and Investigations

Referral

Urgently refer people via a suspected cancer pathway (for an appointment within 2 weeks) if the patient is ≥45 years old and any of the following apply:

• Unexplained visible haematuria without a urinary tract infection (UTI)
• Visible haematuria that persists/recurs after successful treatment of a UTI

Investigations

Key investigations include:

• Contrast-enhanced CT or MRI abdomen and pelvis:
  • Diagnostic for RCC and used in staging
  • MRI may be used if contrast media is contraindicated (e.g. allergy or poor renal function)
• Renal biopsy may be considered:
  • This is not routinely done if there is a malignant renal mass with no metastases as this would not significantly change management. These patients are usually offered surgical resection and histological confirmation is done on the removed tissue.
  • However, some indications are if RCC is indeterminate, metastatic, medical management may be implemented, or alternate diagnoses are being considered

Some other investigations may include:

• Full blood count (FBC):
  • May show anaemia of chronic disease or polycythaemia due to paraneoplastic erythropoietin secretion
• Urea and electrolytes (U&Es) and calcium:
  • May show renal dysfunction
  • May show hypercalcaemia due to paraneoplastic parathyroid hormone-related protein secretion
• Urinalysis:
  • Shows haematuria and/or proteinuria, but these findings are non-specific
• Liver function tests (LFTs):
  • May show elevated transaminases due to hepatic metastases
  • May show cholestatic liver function tests due to Stauffer syndrome
• Abdominal ultrasound:
  • May identify suspicious masses, but not useful for diagnosis or further assessment

Staging

The tumour, node, metastasis (TNM) staging system is used for renal cell cancer. TNM stage grouping is used in renal cell cancer which helps guide management. It uses features of the TNM staging system to group renal cell cancer into stages I-IV with IV having the worst prognosis.

Management

Overview

Management is coordinated by a multidisciplinary team. In summary: 

• If confined disease: partial or total nephrectomy depending on tumour size
• Immunotherapy may be used in metastatic disease (e.g. interferon-α or interleukin 2)
• Renal cell cancer is generally resistant to standard chemotherapy
• Radiotherapy may be used

Prognosis

• People with stage I RCC have 5-year survival rates >85%, but this decreases to >75% with stage II, and >10% with stage IV