Key Facts

RCC is the most common solid renal tumour. The incidental detection rate has increased due to widespread cross-sectional imaging, improving stage at diagnosis.

Epidemiology

• ~13,000 new cases/year in the UK (7th most common cancer)
• Peak age 60-70 years; M:F 2:1
• Incidence increasing (partly due to incidental detection)
• 5th most common cancer in males in the UK

Aetiology

• Risk factors: smoking (30% increased risk), obesity, hypertension, chronic dialysis (acquired cystic disease)
• Genetic syndromes: VHL syndrome (clear cell), hereditary papillary RCC (MET mutations), BHD syndrome
• VHL gene (chromosome 3p): tumour suppressor; loss of function → HIF accumulation → VEGF overexpression

Pathophysiology

• Arises from renal tubular epithelium
• Clear cell (70-80%): VHL inactivation → HIF-driven angiogenesis; highly vascular tumour
• Papillary (10-15%): type 1 (MET) and type 2
• Chromophobe (5%): arises from intercalated cells; better prognosis
• Collecting duct (<1%): aggressive
• RCC has tropism for venous invasion (renal vein → IVC → right atrium in 5-10%)

Local Symptoms

• Haematuria: painless, macroscopic (most common presenting symptom)
• Loin/flank pain: dull aching
• Palpable mass: in advanced disease
• Classic triad present in <10% of cases

Systemic/Paraneoplastic

• Pyrexia of unknown origin (20%)
• Weight loss, fatigue, anorexia
• Polycythaemia: ectopic EPO (3-5%)
• Hypercalcaemia: PTHrP secretion
• Hypertension: renin secretion
• Stauffer syndrome: non-metastatic hepatic dysfunction (raised ALP, hepatosplenomegaly)
• Left varicocele: left renal vein obstruction (pathognomonic for left RCC)
• Amyloidosis: AA type (rare)

Metastatic Disease (25% present with metastases)

• Lung (75%), bone (20%), liver (18%), brain (8%)
• Cannonball metastases on CXR (classic)

Red Flags

• Painless haematuria in adults → urgent investigation (2-week wait referral)
• New left varicocele → left renal mass
• Unexplained PUO + raised ESR → consider RCC

Bedside

• Urinalysis: haematuria
• BP: hypertension

Bloods

• FBC: polycythaemia (EPO) or anaemia (chronic disease)
• U&Es: renal function
• Calcium: hypercalcaemia (PTHrP)
• LFTs: Stauffer syndrome (raised ALP)
• ESR/CRP: often elevated
• LDH: prognostic marker

Imaging

• CT abdomen with contrast (triphasic): gold standard; characterises mass, staging, vascular invasion
  • Bosniak classification for cystic lesions (I-IV)
• CT chest: lung metastases
• MRI: if IVC thrombus suspected; superior for vascular detail
• Bone scan: if bone pain or raised ALP
• CT/MRI brain: if neurological symptoms

Special Tests

• Renal biopsy: not routine for surgical candidates; indicated if lymphoma suspected, small renal mass in comorbid patient, or if metastatic disease with unknown primary
• PET-CT: limited role in RCC (variable FDG uptake); more useful for detecting recurrence

Localised Disease (T1-T3)

• Partial nephrectomy: T1a (≤4cm); nephron-sparing; preferred when technically feasible
• Radical nephrectomy: T1b-T3; includes kidney, Gerota's fascia, ± adrenalectomy, ± lymph node dissection
• Active surveillance: small renal masses (≤3cm) in elderly/comorbid patients; growth rate monitoring with serial imaging
• Ablation (radiofrequency/cryoablation): alternative for small tumours in patients unfit for surgery

Locally Advanced (T3-T4 with IVC Thrombus)

• Radical nephrectomy with IVC thrombectomy (may require cardiopulmonary bypass for right atrial extension)

Metastatic RCC

• Cytoreductive nephrectomy: consider in selected patients with good performance status
• First-line systemic therapy (NICE approved):
  • Nivolumab + ipilimumab (CheckMate 214): intermediate/poor risk
  • Pembrolizumab + axitinib (KEYNOTE-426): all risk groups
  • Cabozantinib (METEOR): all risk groups
  • Sunitinib 50mg/day (4 weeks on, 2 weeks off): TKI; historical standard
  • Pazopanib 800mg/day: alternative TKI
• Second-line: nivolumab monotherapy, cabozantinib, lenvatinib + everolimus

Referral Criteria

• Any suspicious renal mass → urology 2-week wait
• Painless macroscopic haematuria → urgent referral
• Metastatic disease → oncology MDT

• Stage I: 5-year survival ~90%
• Stage II: 5-year survival ~75%
• Stage III: 5-year survival ~60%
• Stage IV: 5-year survival 10-15% (improved with immunotherapy)
• Checkpoint inhibitors have improved median OS in metastatic RCC from ~15 months to >45 months
• Late recurrence can occur >10 years after nephrectomy (lifelong surveillance recommended)
• Spontaneous regression of metastases after nephrectomy: extremely rare (<1%) but well-documented

RCC Subtypes

IMDC Prognostic Criteria (Metastatic RCC)

Favourable (0 factors), Intermediate (1-2), Poor (3-6)