Bladder cancer

Bladder cancer is a common malignancy, in 2017 it was the 11th most common cancer in the UK.

In the UK, transitional cell carcinoma is by far the most common cause (around 90%). Advancing age and smoking are significant risk factors for its development.

More men than women are affected, though this appears largely due to exposure to relevant risk factors.

It classically presents with painless haematuria. Management depends on staging and can involve trans-urethral resection of bladder tumour (TURBT), immunotherapy, chemotherapy, radiotherapy and cystectomy.

There are approximately 10,300 cases of bladder cancer in the UK each year.

In 2017, bladder cancer was the 11th most common cancer in the UK, accounting for 3% of new cancers. It is responsible for around 5,500 deaths.

It affects more men than women, in 2017 it was the 8th most common cancer in men (7,400 cases) and the 16th most common in women (2,800 cases).

It occurs more frequently in White people when compared to those of Black or Asian heritage. The most common age group affected is those between 85-89.

Fortunately over the past decade rates have been falling and are projected to keep falling (by up to a third from 2014 to 2035).

For more facts and figures check out Cancer Research UK (last accessed Nov 2021).

Transitional cell carcinoma is the most common cause of bladder cancer in the UK.

Transitional cell carcinoma

Transitional cell carcinomas (TCC), also named urothelial carcinoma, arise from the transitional (urothelial) epithelium. This is a specialised epithelium that lines the urinary tract from the collecting ducts of the kidneys down to the proximal urethra. In the Western world, TCCs are responsible for around 90% of cases of bladder cancer.

There are a number of risk factors associated with TCC:

• Smoking (most important risk factor!)
• Age
• Occupation and chemical associated exposures (e.g. arylamines, polycyclic aromatic hydrocarbons)
• Medications (e.g. cyclophosphamide)
• Radiotherapy

Squamous cell carcinoma

Squamous cell carcinomas (SCC) arise from epithelial squamous cells. Its development is strongly linked with exposure to schistosoma haematobium, a parasitic fluke found in fresh water in some tropical (and subtropical) regions. Whilst SCC only accounts for around 3-5% of cases in the Western world, in areas where schistosoma haematobium is endemic it can be the cause in around 75% of cases.

Schistosoma haematobium causes an infection called schistosomiasis (or bilharzia) after the person comes into contact with contaminated water. It can cause an acute illness with chronic disease developing in some individuals. In the urinary system it can cause haemorrhagic cystitis and eventual malignancy.

It is not the only risk factor for bladder SCC, others include chronic cystitis/UTIs and radiotherapy.

Others

The other causes of bladder cancer are all relatively rare. Adenocarcinomas account for around 2-3% of cases. Non-epithelial bladder cancers (e.g. sarcoma) are all very rare.

The classical presentation of bladder cancer is macroscopic (visible) haematuria.

• Haematuria (micro or macroscopic)
• Dysuria
• Urgency
• Urinary frequency

Patients may also develop symptoms of advanced disease. These include pelvic pain, flank pain, bone pain, peripheral oedema, anorexia and weight loss.

All patients with suspected bladder cancer should be referred via an urgent (two-week wait) cancer pathway.

NICE guidance NG12, Suspected cancer: recognition and referral advise urgent referral on the suspected cancer pathway if:

• Age 45 or over and have unexplained visible haematuria without urinary tract infection.
• Age 45 or over and have visible haematuria that persists or recurs after successful treatment of urinary tract infection.
• Aged 60 and over and have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test.

Additionally they advise referral in those aged over 60 with recurrent or persistent unexplained urinary tract infection.

There are other triggers for referral for unexplained symptoms (e.g. weight loss, anorexia), and clinical judgment must be used.

Cystoscopy is the diagnostic modality of choice.

Blood tests

• FBC
• UE
• LFT

Urinary

• Urine dip & MSU
• Urinary cytology

Cystoscopy

The diagnostic standard, cystoscopy allows visualisation of the bladder and for biopsies to be taken. It can be diagnostic and therapeutic allowing TURBT to be completed.

Imaging

• USS
• CT
• MRI

Imaging may be important to evaluate for other causes of presentation (e.g. renal carcinoma) or where advanced disease is suspected. In particular, CT or MRI should be considered prior to TURBT if muscle-invasive disease is suspected.

CT or MRI may be used for staging in patients with muscle-invasive, or high-risk non-muscle-invasive bladder cancer. PET-CT may also form part of the staging work-up.

Bladder cancers are staged using the TNM classification system.

The tumour, node and metastasis (TNM) classification is used for bladder cancer. It assigns a score for each of the primary tumour, nodal spread (if any) and distant metastasis. The full staging is beyond the scope of this note but can be found on this EAU page.

Bladder cancer is frequently divided into non-muscle-invasive bladder cancer and muscle-invasive (i.e. the cancer has invaded the detrusor muscle) bladder cancer as this is key to management (see below). The terms superficial and deep bladder cancer are no longer used.

Management options are generally categorised based on the presence or absence of muscle invasion.

There are a number of treatment options for bladder cancer. This is based upon the stage and grade of disease and patient factors, decisions are guided by specialist MDTs.

As a student it is important to be aware of the general management options:

• Trans-urethral resection of bladder tumour (TURBT): this can be completed during cystoscopy with the tumour (or suspected tumour) resected from the bladder. Detrusor muscle should be obtained with TURBT, if not, repeat must be considered. It gives a histological diagnosis allowing depth of invasion to be gauged and is used as the primary treatment of non-muscle invasive bladder cancer.
• Intravesical Bacillus Calmette-Guérin (BCG): intravesical means within the bladder, BCG is a live attenuated vaccine used in the treatment of TB. It is used as an immunotherapy in the treatment of bladder cancer where it is thought to stimulate the immune system to attack cancer cells.
• Intravesical mitomycin C: mitomycin is an antibiotic that has anti-neoplastic effects. It is given following TURBT to reduce the risk of recurrence.
• Radical cystectomy: involves the removal of the entire bladder, used in muscle-invasive bladder cancer. It requires urinary diversion, this is typically achieved by removing a segment of the ileum which is used as a conduit. The ureters are plugged into the ileal conduit and an end of ileum is brought to the abdominal surface as a urostomy (i.e. urostomy and ileal conduit).
• Radical radiotherapy: involves irradiating the bladder in an attempt to cure the cancer, used in muscle-invasive disease. A radiosensitiser (e.g. mitomycin in combination with fluorouracil) is given alongside the radiotherapy.
• Chemotherapy: may be given neoadjuvant (given before primary treatment) or adjuvant therapy (given after primary treatment) in conjunction with radical cystectomy or radiotherapy. It can also be used as primary therapy in those with locally advanced/metastatic disease. Regimens are often cisplatin-based (other agents may be used in conjunction with it), cisplatin is a platinum-based chemotherapeutic that interferes with normal DNA synthesis.

Non-muscle-invasive bladder cancer

TURBT forms the cornerstone of management in non-muscle-invasive cases. This allows for both histological diagnosis and treatment. A single dose of intravesical mitomycin C is offered in suspected cancer during the first TURBT.

Patients at moderate risk (based on the stage and grade) are offered a course of intravesical mitomycin C. Patients with high-risk disease will typically have a repeat TURBT within 6 weeks. They can be offered intravesical BCG or radical cystectomy. This decision will be taken by the patient in conjunction with their urologist and nurse specialist taking multiple factors into account.

Cisplatin-based neoadjuvant of adjuvant chemotherapy is generally offered before radical cystectomy or radical radiotherapy. All patients will need follow-up (determined by risk) to monitor for resolution and recurrence.

Based on NICE guidance (NG 2): Bladder cancer: diagnosis and management.

Muscle-invasive bladder cancer

Management is complex and dependent on numerous factors. Specialist urology MDTs should review each case to guide management. In suitable patients, neoadjuvant cisplatin chemotherapy can be offered prior to radical cystectomy or radical radiotherapy.

The choice of radical cystectomy or radical radiotherapy (with a radiosensitiser) should be discussed (involving oncologist, urologist and nurse specialists) with the patient. All patients will need follow-up tailored to their disease and management.

Based on NICE guidance (NG 2): Bladder cancer: diagnosis and management.

Locally advanced/metastatic bladder cancer

Generally, cisplatin-based chemotherapy is offered to suitable patients. Input from palliative care specialists is indicated in most cases. Many patients with advanced disease have troublesome symptoms, as such attention must also be paid to symptomatic control. This includes:

• Intractable bleeding: persistent haematuria can be troublesome and require blood transfusions. Treatment options include radiotherapy and embolisation (an interventional radiology procedure where selected feeder vessels are blocked with coils).
• Ureteric obstruction: obstruction of the ureters prevents urine from draining into the bladder. This results in renal failure (due to elevated pressure being transmitted to the kidneys) and elevates the risk of serious urinary tract infections (due to stagnant urine). Treatment options include a percutaneous nephrostomy (a tube is placed in the back through the skin into a renal calyx allowing draining of urine via this tube) or a retrograde stent (stent inserted during a cystoscopy).
• Pelvic pain: troublesome pelvic pain is common and normal analgesia may not be sufficient. Options include radiotherapy, chemotherapy and nerve blocks.
• Bladder symptoms: includes urinary frequency, urgency, nocturia and dysuria that can impact quality of life. Radiotherapy may be given to help reduce these symptoms in those with incurable disease.

Prognosis is strongly linked to the stage of disease at the time of diagnosis.

The below figures are taken from Cancer Research UK (accessed Nov 2021).

• 74.1% survive one year or more after their diagnosis
• 52.6% survive five years or more after their diagnosis

Younger patients have longer survival, almost 75% survive five years or more if aged 15-49 at diagnosis. This is compared to around 40% in those aged 80 or older.