Urological Malignancy

Core

Introduction

The term urological cancer is used to describe cancers of the urinary system, for example kidney and bladder cancer. Urological cancers are fairly common in the UK. The main two types of urological cancer are renal cell carcinomas, which are more common in the kidney, and transitional cell carcinomas, which are more common in the bladder. 

One of the main presentations of urological malignancy is haematuria, which can be visible or invisible (found on a urinary dipstickThis is important as patients presenting to the GP with unexplained haematuria may require an urgent two week wait referral to urology, depending on age and associated features.

• Aged 45 and over with:
• Unexplained visible haematuria without urinary tract infection, or
• Visible haematuria that persists or recurs after treatment of urinary tract infection. 
• Aged 60 and over with:
• Unexplained non-visible haematuria and either dysuria or a raised white cell count, or
• Recurrent or persistent unexplained urinary tract infection.

Renal Cell Carcinomas

Renal cell carcinomas (RCCs) are the most common renal cancerIt mostly affects the kidney but can involve other parts of the urinary system; however, for this article we will focus on renal cell carcinoma of the kidney.transitional cell carcinomas, nephroblastomas and squamous cell carcinomas.  

Renal cell carcinomas are adenocarcinomas that arise from the proximal renal tubular epithelium, and they usually appear histologically as clear cell carcinomas, so called because the cells contain abundant glycogen and lipid.papillary, chromophobe and renal medullary carcinoma. 

They can arise anywhere within the renal cortex and may spread by direct invasion into surrounding tissue, followed by lymphatic and haematogenous spread.

Risk Factors

• Smoking
• Male
• Obesity
• Dialysis
• Hypertension 
• Industrial exposure to carcinogens
• Family history - a small number of renal cell carcinomas have a genetic aetiology  

Signs and Symptoms 

• Haematuria - this is one of the main symptoms of renal cell carcinomas. It can either be visible or invisible.
• Flank or loin pain 
• Weight loss
• Lethargy 
• Fever 
• Palpable abdominal mass - if a patient with renal cell carcinoma has a palpable abdominal mass then it typically means the malignancy is quite advanced. 
• Paraneoplastic syndromes - these are a group of syndromes that occur as a result of the malignancy and occur in around 20% of patients. In RCCs the main paraneoplastic syndromes are caused by hormone secretion:
• Renin - increased renin secretion causes hypertension. 
• Parathyroid hormone-related peptide (PTHrP) - increased secretion results in hypercalcaemia.
• Erythropoietin - increased erythropoietin production causes polycythaemia as it increases the production of red blood cells. 
• Adrenocorticotropic hormone - results in Cushing’s syndrome due to a raised cortisol level. 
• Left-sided varicocele - if a renal cell carcinoma impinges on the left testicular vein then it can cause a build up of blood within the testicular venous plexus causing a varicocele. 
• This is classically associated with left sided RCCs, as the left gonadal vein drains into the renal vein and can be compressed by a tumour, whereas the right gonadal vein drains directly into the inferior vena cava.

Investigations 

If a patient is suspected to have a renal cell carcinoma then they will be referred to urologyThe first line investigations for renal cell carcinoma are blood tests, urinalysis and imaging.imaging to identify the site and size of the lesion. 

• The main blood tests to undertake are a full blood count, urea and electrolytes, calcium and liver function tests. 
• Urinalysis will be used to look for haematuria which is a red flag for urological malignancy while the urine cytology will look for malignant cells in the urine.  
• Some renal cell carcinomas can be asymptomatic and are picked up as an incidental finding on imaging. 
• Ultrasound, CT and MRI scans are used in the imaging in renal cell carcinoma as they can identify the lesion and can help in carrying out a biopsy of the lesion. A CT chest-abdo-pelvis scan may be done to look for metastases that may be present. 
• CT and MRI scans are performed with and without contrast to ensure any RCC is not missed. 
• Biopsy of the malignancy is usually only performed if the tumour is not going to be excisedA core needle biopsy is performed in these patients, which can help guide the choice of systemic therapy.
• Those who have surgical excision of the tumour will have it sent to pathology so that the type of renal cell carcinoma can be defined. 

The TNM staging system is used to stage renal cell carcinomas as this gives an idea about the prognosis of the malignancy, with a Stage I RCC having a 90% 5 year survival, while a Stage IV RCC only has a 10% 5 year survival. 

Management

The management of renal cell carcinoma depends on the size of the cancer and on the presence of metastases. Those with local disease typically undergo surgical excision of the malignancy while those with metastatic disease undergo surgical excision with systemic immunotherapy. 

• Surgical excision is the main treatment for local renal cell carcinomas and for those with lymphatic metastases. The two main types of surgical excision are:
• Partial Nephrectomy - this is where only part of the kidney is removed. It is either performed by open, laparoscopic (keyhole) or by robotic surgery. Only small RCCs are removed by partial nephrectomy.
• Radical Nephrectomy - this is where the whole kidney is removed, along with the adrenal gland and the fat surrounding the kidney. This can be either open surgery or laparoscopic and is for RCCs that cannot be excised by partial nephrectomy. 
• Ablative therapies can be used to destroy some small tumours, though these tumours must have had a biopsy first to check they are susceptible to ablation. Ablative therapies include cryoablation, radiofrequency ablation and . 
• Metastatic disease is treated depending on the number of metastases. Those with metastatic disease are categorised as stage IV and so have a very poor prognosis, this means the main aim of treatment is palliative care to slow disease progression and to help the patient remain comfortable. 
• If there is only a solitary metastatic lesion then cytoreductive nephrectomy is undertaken, which involves the removal of as much of the renal tumour as possible. This is coupled with systemic immunotherapy with or without metastatectomy (surgical resection of solitary metastasis).
• If there are multiple metastatic lesions then the main treatment is systemic immunotherapy. Cytoreductive nephrectomy may also be performed in those with a more favourable prognosis. 

Transitional Cell Carcinomas 

The urinary system is lined by transitional cell epithelium, the urothelium, so it is at risk of developing a transitional cell carcinoma (TCC). The majority of TCCs are found in the bladder but they can also be found in the upper urinary system, i.e. in the kidney and ureter. This article will focus on bladder transitional cell carcinomas. 

Bladder Transitional Cell Carcinomas 

Bladder transitional cell carcinomas (TCCs) are the most common urological malignancy in the UK and typically affect men aged 50-80 years. Other bladder cancer types include squamous cell carcinomas and adenocarcinomas, though these are less common in the UK. 

Bladder cancers are classified by how far the cancer invades into the muscle of the bladder wall. There are three main classifications:

• Non-Muscle Invasive - the bladder cancer does not penetrate into the deeper layers of the bladder wall and remains quite superficial. 
• Muscle Invasive - the bladder cancer penetrates into the deeper layers of the bladder wall but not into surrounding structures. 
• Locally Advanced - the bladder cancer penetrates through the entire bladder wall and spreads beyond the bladder, into the surrounding structures. 

Risk Factors

• Smoking - this is the greatest risk factor for transitional cell carcinoma. 
• Occupational exposure - some occupations have an increased risk of bladder cancer because of the carcinogens they are exposed to in the work environment, e.g. rubber/plastic manufacturer, crude oil, smelting, painter, mechanic and hairdresser. 
• Caucasian 
• Male 
• Chronic irritation - e.g. infection, schistosomiasis, bladder stone and long term catheter. These typically increase the risk of bladder squamous cell carcinomas and not transitional cell carcinomas. 
• Cyclophosphamide 

Signs and Symptoms 

• Haematuria - this may be macroscopic (visible) or microscopic (invisible, picked up on a urinary dipstick). Patients typically present with macroscopic haematuria in bladder cancer. 
• Lower urinary tract symptoms - these include nocturia, urgency, frequency, incomplete emptying, terminal dribble, hesitancy, straining and post-micturition dribble.
• Recurrent urinary tract infections  
• Pelvic pain - patients may present with pelvic pain if they have locally advanced disease. 
• Pelvic mass 
• Weight loss
• Loss of appetite
• Urinary retention - patients may present with urinary retention if the tumour obstructs the internal urethral orifice. 
• Systemic symptoms of metastases if late stage. 

Bladder carcinomas may be an incidental finding on imaging that was done to investigate something else. 

Investigations 

Bladder transitional cell carcinomas are investigated by cystoscopy, blood tests, ultrasound scan, MRI and CT scans. Urinalysis is also used to check for blood in the patient's urine as haematuria is an indicator of bladder TCCs. 

Cystoscopy is the main investigation used for transitional cell carcinomas. A flexible cystoscopy is used to visualise the bladder and assess for any suspicious lesions, and is usually the first investigation performed if bladder malignancy is suspected. If a suspicious lesion is found then a rigid cystoscopy is performed to biopsy the lesion if it is large, or remove the lesion if it is small. A transurethral resection of the bladder tumour may be performed during the rigid cystoscopy if the tumour is small. 

An ultrasound scan can be used to look for any lesions prior to cystoscopy, and is also used to check for urinary retention if indicated. A pelvic MRI or CT scan are used to assess the size of the bladder malignancy and see if it has invaded into the muscle wall or surrounding structures. MRI and CT scans can also be used to look for any metastases.  

It is also important to check the patient’s renal function and full blood count (for anaemia and infection). Other blood tests to do include liver function and alkaline phosphatase. A raised alkaline phosphatase may raise suspicion of bone involvement, and further imaging such as a bone scan may be considered in the appropriate clinical context. 

Management

The treatment of bladder transitional cell carcinoma depends on whether the tumour has invaded into the muscle wall or if it has metastasised. Bladder TCCs use the TNM staging system to stage the severity of the bladder malignancy.  

Non-muscle invasive TCCs are treated by transurethral resection of the bladder tumour (TURBT), which involves going in through the urethra and removing the tumour. The tumour can then be sent off to pathology for further analysis. 

• Other treatments for non-muscle invasive TCCs include intravesical cytotoxic chemotherapy and intravesical BCG. Cytotoxic chemotherapy involves injecting chemotherapy directly into the tumour area after surgery to reduce the risk of recurrence. Intravesical BCG is an immunotherapy that can be used to decrease the risk of recurrence. 
• Superficial bladder tumours have a high rate of recurrence so patients will require regular surveillance with cystoscopy and cytologySurveillance is continued according to risk stratification, with low-risk disease followed up for a shorter period and high-risk disease often requiring long-term or lifelong surveillance.

Muscle invasive TCCs are treated with either cystectomy or chemoradiation. Cystectomy is the removal of the bladder along with the prostate in men, and the uterus and ovaries in women. Neoadjuvant chemotherapy is often given before the cystectomy as it increases patient survival rate. After cystectomy, patients require regular follow-up with a CT scan. 

• After a cystectomy, patients require either an ileal conduit formation or bladder reconstruction. In ileal conduit formation, part of the ileum is used to form a urostomy, where the urine then drains from. Bladder reconstruction involves using part of the small bowel to form a new bladder, with urine then being drained by the urethra or the catheter. 
• Chemoradiotherapy is the other treatment for muscle invasive TCCs, where patients are treated with both systemic chemotherapy and targeted radiotherapy. 

Metastatic disease is treated with the intention to control symptoms and prolong survival of the patient as metastatic disease is incurable, so is treated palliatively. The management is decided by a multi-disciplinary team and is split into measures for local disease and for systemic disease. 

• Local treatment includes radical cystectomy and urinary diversion, both for symptomatic relief. Radiotherapy can also be directed at the tumour site either before or instead of surgery. 
• Systemic treatment includes chemotherapy (and, in selected patients, immunotherapy). Radiotherapy is used for local or palliative control of symptomatic metastases rather than as a systemic treatment. 
• Patients will have regular follow-ups and reviews for detection and treatment of progressive disease and to treat any new symptoms that may develop.

Edited by: Dr. Maddie Swannack

Reviewed by: Adrian Judge

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