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)
- IVCInferior vena cava invasion → bilateral lower limb oedema +/- lower abdominal wall oedema
- Hepatic vein obstruction (tumour thrombus reaching the hepatic vein–IVCInferior vena cava junction) → Budd-Chiari syndrome (triad of RUQ pain + hepatomegaly + ascites)
Renal cancers are highly venotropic (highly propensity for invading veins).
Metastatic Features
| Pulmonary metastasis (most common) | Presents as cough, dyspnoea, haemoptysis
Chest X-ray classically shows cannonball metastases Multiple large, round pulmonary nodules |
| Bone metastasis (2nd most common) | Presents as:
|
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 UTIUrinary tract infection, or
- Visible haematuria that persists or recurs after successful treatment of UTIUrinary tract infection
Investigation and Diagnosis
Imaging
1st line imaging: multiphasic contrast-enhanced CT abdomen
Other:
- MRI abdomen – if CT is unsuitable / inconclusive
- Contrast-enhanced ultrasound – may be considered if CT and MRI are unsuitable / inconclusive
Once possible renal cancer is confirmed → offer CT chest and pelvis for staging
Important imaging features that suggest renal cancer, over a simple renal cyst:
- Enhancement post-contrast administration – most important
- Typically, a solid renal mass with heterogeneous enhancement (often due to necrosis / haemorrhage)
- Simple renal cysts are homogeneous and show no contrast enhancement
- Irregular outline that distorts the cortex (round / oval mass with a sharply defined outline is more likely a cyst)
- Thick, irregular, enhancing wall / septa
- Local invasion (e.g. fat stranding, renal vein, IVC thrombus)
Renal Biopsy
Renal biopsy is not routinely required in all patients with suspected RCCRenal cell carcinoma. It is reserved for cases where histological confirmation would influence management.
Decisions regarding when to offer renal biopsy is often at specialist-level, key recommendations from NICE are presented below for completeness.
| Offer renal biopsy if: |
|
| Consider renal biopsy if: | Lesion >4 cm + has a solid component that is large enough to obtain tissue sample from + ANY of the following:
|
| When NOT to do renal biopsy: |
|
Other Investigations
These findings are non-specific for RCC but are high-yield for exams.
| FBC |
|
| U&E |
|
| LFTs | Deranged LFTs are seen in Stauffer syndrome (a paraneoplastic syndrome, NOT due to liver metastasis):
|
| Urinalysis |
Urinalysis is essential to assess for concurrent UTIUrinary tract infection, which is a common alternative cause of haematuria. |
Management
Disclaimer:
NICE guidance specifically addresses RCCRenal cell carcinoma. For non-specialist learning, this distinction has limited impact on core management principles.
Prior to the recently published NICE NG256 guideline (Mar 2026), most teaching (including this article) was based on EAUEuropean Association of Urology guidelines, which emphasise TNM staging. Traditionally, a 7 cm cut-off was used to guide surgical approach (partial vs radical nephrectomy). Current NICE guidance instead emphasises individualised decision-making based on tumour size, technical feasibility, and patient factors.
Localised Renal Cell Carcinoma (RCC)
Approach:
| Surgical candidate? | Tumour size | Recommended approach |
|---|---|---|
| <2 cm | Consider active surveillance
If patient declines → consider surgery |
|
| Yes | ≥2 cm | Offer surgery
If not suitable for surgery → see below |
| No | 2-4 cm | Consider active surveillance OR thermal ablation
If both unsuitable → consider SABRStereotactic ablative radiotherapy |
| >4 cm | Consider thermal ablation or SABRStereotactic ablative radiotherapy |
Key principles:
- Tumours <2 cm → active surveillance is appropriate
- Tumours ≥2 cm → surgery is preferred if suitable
- If not suitable for surgery → consider active surveillance, thermal ablation, or SABR depending on tumour size and patient factors
Active Surveillance
Surveillance is primarily imaging-based (CT / MRI / ultrasound):
- Year 1: at 3-6 months, then at 12 months
- Years 2-5: at least annually
- Consider discharge after 5 years if stable (after discussing risk and benefits)
Switch to active treatment should be considered if ANY of the following:
- Growth rate >5 mm/ year
- Tumour size like to be >4 cm by the time of the next scan
- Change in clinical circumstances (e.g. pregnancy, comorbidities)
- Stage progression (TNM)
- Patient preference
Surgery
There are 2 main options for surgery:
| Surgical approach | Description |
|---|---|
| Partial nephrectomy | Preferred if:
|
| Radical nephrectomy | Preferred if:
|
Pembrolizumab is recommended as an option for adjuvant treatment post-nephrectomy if patient is at increased risk of recurrence.
Earlier guidelines (e.g. EAUEuropean Association of Urology) used a 7 cm cut-off to guide the choice between partial and radical nephrectomy.
However, latest NICE guidance emphasises individualised decision-making based on technical feasibility and patient factors.
Metastatic Renal Cell Carcinoma
Systemic anti-cancer therapy is the mainstay of management
- 1st line treatment typically involves immune checkpoint inhibitors and/or tyrosine kinase inhibitors (guided by risk stratification)
- Immune checkpoint inhibitors examples: pembrolizumab, nivolumab
- Tyrosine kinase inhibitor examples: tivozanib, pazopanib, sunitinib
Chemotherapy is generally ineffective in renal cancer.
Renal cancer is resistant to chemotherapy because of high drug-efflux pump activity, low tumour proliferative rate, strong anti-apoptotic signalling, and its unique VEGF-driven tumour biology.
Other options (specialist-level):
- Cytoreductive nephrectomy may be considered to treat the primary lesion (assuming surgery is suitable):
- Before systemic anticancer therapy when immediate systemic therapy is not indicated (e.g. due to oligometastatic disease)
- After systemic anticancer therapy in selected responders when most remaining disease is in the primary renal lesion
- Persistent symptoms that could be controlled by surgery (e.g. bleeding or pain) – before or after systemic anticancer therapy
- Consider the following to treat metastases
- External beam radiotherapy
- Metastasectomy
- Thermal ablation
References
NICE guideline Kidney cancer: diagnosis and management