Kidney cancer is the 7th most common cancer in the UK that accounts for approximately 4% of all cancer cases. There are approximately 13,000 new cases of renal cancer diagnosed in the UK annually.
It is more common in men than in women, with the elderly population more adversely affected (85-89 years has the highest incidence).
Approximately 25% have metastasis at presentation.
Pathophysiology and types
The majority of kidney cancers (or renal cell carcinomas specifically) are sporadic. There are genetic syndromes associated with kidney cancer, such as Von Hippel-Lindau (VHL) syndrome, and Birt-Hogg-Dubé syndrome
Other genes implicated include succinate dehydrogenase (SDHB), MET and BAP1. These are all inherited in an autosomal dominant fashion.
Tobacco exposure also promotes cancerous changes in the kidneys due to oxidative stress and nitrosamine exposure. Hypertension increases tubular assault and increases exposure to carcinogens.
Let’s discuss some of the types of kidney cancers that are seen based on the hisotological subtypes:
- Renal cell carcinoma (RCC) - the most common renal cancer. It is an adenocarcinoma of the renal cortex. It often arises from the proximal convoluted tubules.
Microscopically RCCs are polyhedral clear cells with dark staining nuclei and lipid-rich and glycogen-rich cytoplasm.
Subtypes:
- Clear cell RCC - 70-90% of RCCs. These are seen as golden-yellow on gross pathology.
- Chromophobe RCC - 3-5% of RCCs. These are seen as large, pale cells.
- Papillary RCC - 10-15% of RCCs. Often bilateral or multifocal.
RCCs spread to the surrounding tissues, adrenal glands, renal veins, IVC. Lymphatic spread may metastasise to the para-aortic, retro caval, and hilar nodes. Through haematogenous spread, RCC may go to lungs, liver and bones and brain.
- Urothelial carcinoma (UC)
- Nephroblastoma
- Squamous cell carcinoma
⚠️ Risk factors
⭐️ Smoking is the most significant risk factor for RCC.
Other risk factors include:
- Obesity
- Hypertension
- Industrial carcinogen exposure - such as cadmium, lead or aromatic hydrocarbons.
- Diet - diets low in mineral and vitamins tend to have increased rates of RCC.
- Anatomical abnormalities - such as horseshoe kidneys or polycystic kidneys.
- End-stage renal failure & dialysis
- Renal transplantation
- Genetic disorders:
- Von Hippel-Lindau syndrome - characterised by the presence of visceral cysts and benign tumours that may become malignant.
- Birt-Hogg-Dubé syndrome - associated with the FLCN gene.
- BAP1 mutant disease
- Tuberous sclerosis
🔢 Staging
TNM staging is the most common staging system for RCC. There is also a correlating number staging system from 1-4 which corresponds to certain TNM stages:
- Stage 1 (T1N0M0) - <7cm and confined to the kidney.
- Stage 2 (T2N0M0) - >7cm and confined to the kidney.
- Stage 3 (T3 or N1M0) - local spread to nearby tissues or veins but not beyond Gerota’s fascia (the renal fascia that separates the perítenla fat from the pararenal fat).
- Stage 4 (T4N2 or M1) - spread beyond Gerota’s fascia, including metastasis.
😷 Presentation
RCCs are often asymptomatic, but may present with a classical triad of:
- Haematuria (visible or non-visible)
- Vague loin pain (or loin mass)
- Palpable renal mass
This triad often indicates advanced disease, however.
Other non-specific symptoms of RCCs include:
- Weight loss
- Fatigue
- Anorexia
- Night sweats
- Fever of unknown origin
- Varicocele - majority are left-sided and this is due to compression of the gonadal internal spermatic vein.
There are certain paraneoplastic features that may also be present:
- Polycythaemia - due to excessive erythropoietin production.
- Hypercalcaemia - due to parathyroid hormone-related protein (PTHrP) secretion.
- Hypertension - due to a number of factors, such as: increased renin secretion, polycythaemia, physical compression of the renal arteries.
- Stauffer’s syndrome (paraneoplastic hepatopathy) - this is when there are abnormal LFTs without liver metastasis. It presents with cholestasis or hepatosplenomegaly. It is believed to be due to an increase of IL-6. IL-6 promotes the release of acute phase proteins but its mechanism of inducing hepatocyte injury is not understood.
- Syndrome of inappropriate ADH
✍️ Referral criteria
NICE states that patients who meet the following criteria are elegible for a 2-week wait referral:
- Aged ≥45 with:
- Unexplained visible haematuria (in the absence of UTI) OR
- Visible haematuria that persists after successful treatment of UTI.
- Aged ≥60 with non-visible haematuria AND dysuria/raised white cell count.
NICE also recommends considering a non-urgent referral in people over 60 with recurrent, unexplained UTIs.
🔍 Investigations
- Bloods - such as FBC, U&Es, calcium levels, LFTs, CRP, coagulation profile.
- Urinalysis and urine cytology
- eGFR - this is important to help guide management.
- 🥇 Ultrasound
- 🏆 IV urogram (contrast-enhanced CTAP) with pre and post-IV contrast.
- Flexible cystoscopy - to rule out bladder cancer.
- CXR - may show cannonball metastases.
Unlike most other cancers, a diagnosis of renal cancer can be made without a biopsy if the imaging modalities are suggestive of renal cancer. However, particularly for small renal masses when surveillance or minimally invasive ablative therapies are considered → biopsy may be considered.
🧰 Management
We will discuss the management for localised disease as well as metastatic disease.
🥇 The first-line option for management is surgical removal:
- Partial nephrectomy - indicated for smaller tumours.
- Radical nephrectomy - indicated for larger tumours. This involves removal of the entire kidney, lymph node, surrounding tissue and possible the adrenal gland (the adrenal gland should be spared where possible).
Survival for patients who have undergone nephrectomy is around 70% at 3 years and 60% at 5 years.
🥈 For patients not fit for surgery:
- Percutaneous or laparoscopic cryotherapy - this involves injection of liquid nitrogen to freeze and kill the tumour cells.
- Percutaneous radiofrequency ablation - using a needle in the tumour coupled with an electrical current to kill the tumour cells.
- Arterial embolisation - cutting the blood supply to the affected kidney.
We also need surveillance of slow growing renal masses.
Patients who are otherwise fit and have metastatic disease, management involves nephrectomy + immunotherapy:
- IFN-α - or IL-2 agents. These work by stimulating the immune system to target the cancer cells.
Biological agents:
- Sunitinib - a multikinase inhibitor. A kinase is an enzyme that works by phosphorylating a substrate using ATP. Sunitinib specifically works through inhibition of VEGF, PDGF which both play a role in both tumor angiogenesis and tumor cell proliferation.
- Pazopanib - another multikinase inhibitor with a similar mechanism of action as sunitinib.
- Metastasectomy - this is surgical resection of solitary metastases. It is recommended when the disease is resectable and the patient is otherwise fit and healthy.
- Chemotherapy is considered ineffective (generally) in patients with renal cell carcinoma.
🚨 Complications
- Anaemia
- Tumour thrombus - when the renal tumour invades the renal vein leading to a blockage and stasis which causes thrombus formation. This thrombus can ultimately encroach into the inferior vena cava and ascend in more advanced stages.
- Paraneoplastic syndromes
