Bladder Cancer

Introduction

Bladder cancer develops from the lining of the bladder and is the most common tumour of the urinary system.

In the UK, it comprises 3% of all cancers cancer types, with the peak age affected being >80yrs and is more common in men than women (ratio 3:1). Fortunately, most diagnosed bladder cancers are superficial (Ta, T1, or CIS) with a good prognosis.

It can be divided into several subtypes, including transitional cell carcinoma (most common, 80-90% cases), squamous cell carcinoma (SCC), adenocarcinoma (rare), and sarcoma (rare).

Bladder cancers can further be classified into:

• Non-muscle-invasive bladder cancer – does not penetrate into the deeper layers of the bladder wall (around 70-80% cases)
• Muscle-invasive bladder cancer – penetrates into the deeper layers of the bladder wall
• Locally advanced or metastatic bladder cancer – spreading beyond the bladder and distally

The Bladder Wall

The bladder wall can be divided into four layers, which are important when classifying bladder malignancies:

• Inner lining of the bladder is called the transitional epithelium (urothelium)
• The second layer is a connective tissue layer called the lamina propria
• The third layer is a muscular layer and is termed the muscularis propria
• The four (outer) layer is the fatty connective tissues

By TeachMeSeries Ltd (2020)

Figure 1 – The internal surface of the bladder, highlighting the trigone

Risk Factors

The most important risk factors for bladder cancer is smoking and increasing age.

Other risk factors include exposure to aromatic hydrocarbons (e.g. industrial dyes or rubbers), Schistosomiasis infection (specifically causing the SCC subtype), and previous radiation to the pelvis.

Clinical Features

The most common presenting features is painless haematuria, either visible or non-visible. Patients may also present with recurrent UTIs or lower urinary tract symptoms (LUTS), such as frequency, urgency, or feeling of incomplete voiding.

Clinical examination, especially in early disease, is typically unremarkable. If the bladder cancer obstructs the ureteric orifice, features of ureteric obstruction may be present.

Those with locally advanced disease may present with localised symptoms, such as pelvic pain, and those with metastatic disease may present with systemic symptoms, such as weight loss or lethargy.

Bladder Cancer Staging

Bladder cancer staging uses the TNM staging (Table 1). A further subtype often included is the Ta stage, defined as non-invasive papillary tumour; T1 can be further divided into T1a and T1b, as can T2 into T2a and T2b, both depending on the depth of the tissue invasion

Table 1 – TNM Staging for Bladder Cancer

Differential Diagnosis

All cases of haematuria require complete work-up, as discussed below, to evaluate for potential bladder cancer. Other common causes of haematuria include urinary tract infections, renal calculi, or prostate or renal cancer.

Investigations

Adapted from Cancer Research UK [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]

Figure 2 – Schematic demonstrating a flexible cystoscopy

All patients with suspected bladder cancer require urgent cystoscopy. This is typically done initially via a flexible cystoscopy under local anaesthetic.

However, if a suspicious lesion is identified from initial cystoscopy, a rigid cystoscopy will be required (typically done under general anaesthetic) for more definitive assessment.

Any tumour identified at rigid cystoscopy will require biopsy and potential resection via transurethral resection of bladder tumour (TURBT), either on initial assessment (if appears superficial) or following biopsy results (if appears invasive).

Imaging is also warranted and any suspected muscle-invasive bladder cancer, prior to any resection is performed at TURBT, requires CT staging to be performed. Patients may have already had initial US or CT imaging as part of haematuria work-up, however ensuring complete staging in all suspected cases is essential.

Urine cytology can also be sent off, in an attempt to identify cancerous cells in the urine*, however this has poor sensitivity and specificity, hence is not routinely done in all centres.

*If cytology shows cancerous cells however cystoscopy shows apparently normal epithelium, random biopsies at cystoscopy should be performed

James Heilman, MD [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]

Figure 3 – CT urogram imaging showing a carcinoma of the bladder

Management

Management of bladder cancer is strongly determined by the classification of the cancer. All cases should be discussed at a specialist multidisciplinary team meeting.

Non-Muscle-Invasive Bladder Cancer

Carcinoma in-situ or T1 tumours can typically be resected via TURBT, the mainstay of management.

Cases with deemed higher risk disease, even in non-invasive, may require adjuvant intravesical therapy, such as Bacille Calmette-Guerin (BCG) or Mitomycin C. These can be done in the outpatient setting.

Radical cystectomy can also be offered to those with high-risk disease or limited response to initial treatments.

Unfortunately, superficial bladder tumours have a high rate of recurrence, with around 70% recurring within 3 years, and these recurrences are more likely to be more invasive. Consequently, these patients require routine follow-up with regular surveillance via cytology and cystoscopy.

Muscle-Invasive Bladder Cancer

For those fit enough to undergo surgical intervention, most cases of muscle-invasive bladder cancer warrant a radical cystectomy, which involves the complete removal of the bladder.

Cancer Research UK [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]

Figure 4 – Schematic showing an ileal conduit with urostomy

Patients will often also be considered for neoadjuvant chemotherapy, typically with a cisplatin combination regimen.

Following radical cystectomy, patients will require urinary diversion; this can be achieved either through:

• Ileal conduit formation with urine draining via a urostomy
• Bladder reconstruction, from a segment of small bowel* (often termed a neobladder) and urine draining urethrally or via catheter

These patients require regular follow-up with CT imaging to monitor for local and distant recurrence.

*Alongside routine bloods, B12 and folate levels should also be checked at least annually due to the resection of part of the ileum during the urinary diversion procedures.

Locally Advanced or Metastatic Bladder Cancer

Patients with locally advanced or metastatic muscle-invasive bladder cancer who are otherwise well should be considered for chemotherapy, typically either a cisplatin‑based regimen or a carboplatin plus gemcitabine-based regime.

Any symptoms of the disease, such as pelvic pain, ongoing bleeding, or urinary frequency, should be also be managed appropriately with specialist advice and input through the MDT. Palliative options should also be discussed with the patient when appropriate.

Prognosis

Patients who have had bladder cancer are at higher risk of developing upper urinary tract tumours and urethral tumours.

Prognosis of the disease is dependent on the disease staging. Patients with superficial disease have a five-year survival between 80-90%, whilst those with muscle-invasive and metastatic disease have rates of 30-60% and 10-15% respectively.