Renal Cell Carcinoma
Written by Esther Yuk Lim Yap
Last Reviewed: September 2019
Review Due: September 2020
Based on the 2016 WHO classification, there are three main histological subtypes:
Clear cell (majority of RCCs, 75-85%)
Papillary (Type 1 and Type 2, 10-15%)
Both clear cell and papillary RCCs originate from the proximal tubules whereas chromophobe RCCs originate from the intercalated cells in the collecting system.
Incidence peaking between 60-70 years old
Male predominance of 1.5:1
Positive family history
Especially in 1st-degree relatives
Lifestyle risk factors
Smoking (best-established risk factor) and obesity (risk increases with an increase in BMI)
2.5 times increased risk of RCC if systolic BP > 160mmHg
e.g., Von Hippel Lindau (VHL) gene mutation in clear cell RCC, MET gene mutation in papillary RCC, and chromosomal loss in chromophobe RCC
SIGNS AND SYMPTOMS2,5
Patients can be asymptomatic with renal masses, however with advances in non-invasive imaging, over half of RCCs present as incidental findings.
Collecting system infiltration can result in clot formation (significant bleeding) with colic
Felt in the abdomen or flank, usually more obvious in thinner individuals
[The classic triad of frank haematuria, flank pain and an abdominal mass is strongly indicative of advanced disease and only occurs in 6-10% of RCCs]
Irreducible scrotal varicoceles
Involvement of the gonadal vein
Bilateral lower limb oedema, ascites and liver function abnormalities
Occurs in 1/3 of patients due to secretion of ectopic hormones, resulting in clinical consequences of hypertension (renin production), polycythaemia (erythropoietin production), and hypercalcaemia (PTHrP production)
Pathogenesis of RCC remains poorly understood but multiple theories exist for different histology patterns.
For clear cell RCCs, the typical abnormality is chromosomal 3p deletion. This segment contains genes such as VHL, BAP-1 and PBRM1 genes. VHL and PBRM1 gene products are tumour suppressors whereas the BAP1 gene plays a role in the ubiquitin-mediated proteolysis pathway. In sporadic clear cell RCC, two-thirds of patients present with VHL gene alterations.
For papillary RCCs, MET genetic mutations and chromosome 7 duplication occurs in the majority of Type 1 subtypes. Fumarate hydratase (FH) genetic mutations occur in Type 2 papillary RCC.
For chromophobe RCCs, a study reveals a combination of chromosomal loss such as 1, 2, 6, 10 etc.
Full blood count
Red blood cell count (RBC), haemoglobin (Hb)
Anaemia of chronic disease (Hb) or erythrocytosis (RBC) - secondary to EPO production
Urea and electrolytes – serum creatinine (Cr)
Increased creatinine - prior to or as a result of RCC
Serum lactate dehydrogenase (LDH)
Elevated in advanced disease
Serum corrected calcium
Elevated in advanced disease
Glomerular filtration rate (GFR)
Baseline kidney function
Screening tool to differentiate between solid and cystic masses
Computed tomography (CT) of abdomen and pelvis
Definitive imaging modality to detect enhancement of malignant lesions post-intravenous contrast administration. Provides information on tumour size, lymph node status and lung metastases for staging.
Magnetic resonance imaging
additional test to further explore the extension of a tumour thrombus in the IVC
Percutaneous biopsy of renal tumour
Biopsy of renal tumour – performed in potential candidates for systemic therapy in the setting of advanced disease. Also reserved for unclassified lesions or small masses in which ablation or active surveillance is considered
Tumour, Node, Metastasis (TNM) staging – advanced staging correlates with worse prognosis
RCC subtype – worst prognosis in clear cell RCC
Fuhrman nuclear grade – independent predictor of poor outcomes
Sarcomatoid changes – associated with aggressive, high-grade RCCs
Presence of tumour necrosis
Microvascular and collecting system invasion
Laboratory parameters (presence of anaemia, neutrophil-lymphocyte ratio, platelet count, CRP and albumin)
The 5-year survival rate after successful resection is around 50%, however, metastases may present many years after nephrectomy.
Features of perinephric and lymphatic invasion are associated with a poor prognosis.
Treatment for patients with RCC are stratified based on TNM staging (T1 and T2 vs. T3, T4 and metastatic disease)
For localised disease (T1-T2), radical nephrectomy (open or laparoscopic) is preferred. Nephron-sparing surgery can be considered if there is a risk of impaired kidney function.
Ablative techniques are usually reserved for non-surgical candidates (e.g., frail elderly patients) or for those with a solitary kidney.
For locally advanced (T3-T4) disease, radical nephrectomy with the objective of total excision is the first-line treatment. Patients suitable for adjuvant treatment with systemic therapy should be referred appropriately to tertiary centres.
For metastatic disease, options include:
For patients with good performance status 4
(IL-2, IFN-α) for those at high risk of relapse post nephrectomy
Such as VEGF inhibitors (sunitinib, pazopanib) for patients unsuitable for surgery
For patients palliative care, palliative nephrectomy and tumour embolisation can be performed for symptomatic relief.
Accounts for 2-3% of all cancers and 85% of primary renal cancers
Highest incidence in developed Western countries such as North America (baseline risk of 1 in 10000) and Europe
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