Background Information

Histology

There are 3 main types of renal cancer:

• Clear cell renal cell carcinoma – most common (~70%)
• Papillary renal cell carcinoma (~13-20%)
• Chromophobe renal cell carcinoma

Aetiology

Most renal cancers are sporadic. Key risk factors include:

• Smoking (~50% of renal cancer patients are current or former smokers)
• Family history
• Obesity
• Hypertension
• Metabolic syndrome

 

5-8% of renal cancers are hereditary, key important associations:

• Von Hippel-Lindau syndrome (autosomal dominant) (30-40% lifetime renal cancer risk)
• Hereditary papillary renal cell carcinoma (autosomal dominant) (100% lifetime risk)
• Tuberous sclerosis (autosomal dominant) (<5% lifetime risk)

Clinical Features

Many renal masses remain asymptomatic until late stages. The majority of renal cancers are detected incidentally during imaging for unrelated symptoms or abdominal diseases.

Local Features

Classic triad (rare, seen in 0.6%):

• Flank pain
• Visible haematuria
• Palpable abdominal mass (flank / loin mass – typically unilateral)

 

Local tumour spread can cause:

• Left renal vein invasion → left-sided varicocele (classically associated with left-sided renal cancer)
• IVC invasion → bilateral lower limb oedema +/- lower abdominal wall oedema
• Hepatic vein obstruction (tumour thrombus reaching the hepatic vein–IVC junction) → Budd-Chiari syndrome (triad of RUQ pain + hepatomegaly + ascites)

Metastatic Features

Pulmonary metastasis (most common)	Presents as cough, dyspnoea, haemoptysis   Chest X-ray classically shows cannonball metastases
Bone metastasis (2nd most common)	Presents as: Bone pain (often spine, pelvis, femur) Pathological fractures Spinal cord compression Hypercalcaemia (may be from bone mets or paraneoplastic)

Paraneoplastic Syndromes

Paraneoplastic syndromes associated with renal cancer: ^[Ref]

• Hypercalcaemia of malignancy (PTHrP related)
• Haematological
  • Anaemia of chronic disease (most common)
  • Thrombocytosis (reactive thrombocytosis)
  • Secondary polycythaemia (from ectopic EPO secretion – rare but classic)
• Hypertension (from renin secretion)
• Stauffer syndrome (non-metastatic hepatic dysfunction with deranged LFTs)

Diagnosis

The majority of renal cancers are detected incidentally during imaging for unrelated symptoms or abdominal diseases.

Red Flags and Referral

Refer via the suspected renal cancer pathway if ≥45 y/o and:

• Unexplained visible haematuria without UTI, or
• Visible haematuria that persists or recurs after successful treatment of UTI

Investigation and Diagnosis

Diagnostic Work-Up

Imaging modality of choice: CT abdomen with IV contrast

• Most renal masses are diagnosed accurately by imaging alone
• Typically a solid renal mass with  heterogeneous enhancement (due to necrosis / haemorrhage / calcification)
• The most important CT criterion for differentiating malignant lesions is the presence of enhancement post-contrast administration

Other Investigations

Standard blood tests may show:

FBC	Anaemia of chronic disease (normocytic anaemia) (most common) Thrombocytosis (reactive thrombocytosis) Secondary polycythaemia (from ectopic EPO secretion – rare but classic)
U&E	Kidney function is often normal (as the contralateral kidney compensates) Hypercalcaemia (from paraneoplastic PTHrP release or bone metastasis)
LFTs	Deranged LFTs are seen in Stauffer syndrome (a paraneoplastic syndrome, NOT due to liver metastasis): Cholestatic LFTs (↑ ALP ↑ GGT ↑ bilirubin) ↑ PT / INR

Urinalysis:

• Haematuria (due to the tumour invading the collecting system → bleeding into urine)
• Mild proteinuria (due to tumour compression/ invasion of renal parenchyma)
• Sterile pyuria

Management

Renal Cancer Staging

Simplified renal cancer staging:

T Stage	Definition
T1	Tumour ≤7 cm, limited to the kidney
T2	Tumour >7 cm, limited to the kidney
T3	Tumour extends into major veins (e.g. renal vein, IVC) or perinephric tissues, but not beyond Gerota’s fascia
T4	Tumour invades beyond Gerota’s fascia (the renal fascia) Although the adrenal gland lies within Gerota’s fascia, any tumours that invade the adrenal gland are automatically T4 In contrast, invasion into other adjacent organs (e.g., psoas muscle, spleen, pancreas, liver, intestines, diaphragm) is considered extension beyond Gerota’s

N Stage	Definition
N0	No regional lymph node metastasis
N1	Metastasis in regional lymph node(s)

M Stage	Definition
M0	No distant metastasis
M1	Distant metastasis present

Management Based on Stage

Localised Renal Cancer

Surgery is the mainstay of management.

 

Summarised recommendations:

Disease stage	Management approach
T1 renal tumour (≤7 cm, confined to the kidney)	Partial nephrectomy (to preserve renal function)
T2 and onwards	Radical nephrectomy is generally necessary For T3-T4 tumours, surgical removal of venous tumour thrombus is recommended Lymph node dissection is recommended for clinically enlarged lymph nodes

Metastatic Renal Cancer

Systemic therapy is the mainstay of management

• 1st line: combination therapy with immune checkpoint inhibitors and tyrosine kinase inhibitors
• Immune checkpoint inhibitors examples: pembrolizumab, nivolumab
• Tyrosine kinase inhibitor examples: axitinib, lenvatinib, cabozantinib

References