Bladder Cancer

What is Bladder Cancer?

Bladder cancer typically refers to cancer that starts in the urothelial cells that line the bladder. The bladder is a hollow muscular organ in your lower abdomen that stores urine.

It is the most common type of cancer in the urinary tract. The predominant type of bladder cancer is transitional cell carcinoma (TCC). While not as common, TCC can also occur in the kidneys, pelvis, ureters or urethra as these structures are also lined by the same urothelial cells that line the bladder.

There are other types of bladder cancers that are rare:

Squamous cells carcinoma
Adenocarcinoma
Small cell carcinoma
Sarcoma

This article will be focusing on TCC.

Bladder cancer is classified into non-muscle-invasive and muscle-invasive types based on the depth of invasion from the innermost lining towards the outer layers of the bladder. Approximately 70% of newly diagnosed urothelial bladder cancers are classified as non-muscle invasive.

What are the Causes and Risk Factors of Bladder Cancer?

Causes of Bladder Cancer

In many cases, the cause of bladder cancer is not known. It typically occurs when abnormal cells grow and multiply quickly and uncontrollably and invade other tissues.

Risks Factors of Bladder Cancer

Having certain risk factors increases your chances of developing bladder cancer, but it does not mean you will get the disease.

Cigarette smoking
Industrial chemicals used in dyes, paint, textiles, rubber and leather products
Chronic bladder irritation/infection
Herbs containing aristocholic acid
Medication such as cyclophosphamide, phenacetin, pioglitazone
Low fluid intake
Male gender
Increasing age
Personal history of bladder cancer
Genetic predisposition eg: Lynch Syndrome, Cowden disease, retinoblastoma

Reducing Risk of Bladder Cancer

Some measures you can take that can reduce your risk include maintaining a healthy lifestyle by not smoking, increase dietary intake of fruits and vegetables, increase daily fluid intake, and avoiding harmful exposure to toxic chemicals.

What are Signs and Symptoms of Bladder Cancer

Bladder cancer may be found in its early stages as it tends to cause symptoms such as:

Blood in urine
Frequent urination
Painful urination
Urinary urgency
Weak urine stream
Fatigue due to low red cell count

Most of the above symptoms are not specific to bladder cancer and can be more commonly explained by non-cancerous causes such as urinary tract infection, urinary stones or enlarged prostate. Regardless, it remains important for anyone with these symptoms to consult doctors early.

How to Screen for Bladder Cancer?

There is no cost-effective screening test for the detection of bladder cancer for healthy average-risk individuals.

Reducing Risk of Bladder Cancer

If bladder cancer is suspected, these tests may be performed to diagnose the disease.

1. Urine Tests

Urinalysis may detect traces of blood and exclude urinary tract infections. Urine cytology may detect cancerous or pre-cancerous cells. However, the yield of this test is not high.

2. Cystoscopy

A thin, long tube with a light source and camera at the tip is inserted into the bladder by a urologist.

3. Biopsy

Abnormal areas of bladder lining can be identified and biopsied. To accurately classify the local extent of bladder cancer, an adequate transurethral resection of bladder tumour (TURBT) is performed. This involves the sampling of abnormal areas deep into the muscular layer of the bladder wall. Samples removed are tested for the presence and grade of cancer and depth of cancer invasion.

Bladder Cancer Diagnosis: How Do I Confirm Which Stage of Bladder Cancer I Have?

The stage of urothelial bladder cancer is determined by the depth of tumour invasion into the bladder muscle and outer layers, spread into nearby lymph nodes and spread to distant sites.

Non-muscle-invasive Bladder Cancer Tis, Ta and T1 tumours are classified as non-muscle-invasive bladder cancers.

Muscle-invasive Bladder Cancer Bladder cancers that have penetrated into the muscular layer of the bladder wall are termed muscle-invasive bladder cancers (T2, T3, T4).

Once muscle-invasive bladder cancer is diagnosed from cystoscopy, imaging studies are used to further define the extent of local invasion, involvement of adjacent lymph nodes and distant spread.

Computer tomography (CT) is cross-sectional imaging routinely performed to obtain this information. CT urogram captures images of the kidneys, ureters and bladder and CT of the chest will exclude distant spread to lungs and lymph nodes in the chest.

Occasionally, magnetic resonance imaging (MRI) urogram is performed when a more detailed visualisation of the extent of direct growth of cancer into the bladder wall and adjacent structures is desired.

Bone scans may also be considered for the detection of bone spread. PET scan is sensitive for the distant spread of bladder cancer but is not very helpful for assessment of the local extent of bladder cancer as the tracer used for this scan is excreted in the urine.

Bladder Cancer Treatment at The Cancer Centre, Singapore

Our doctors will work closely with you to decide which treatment option is the most suitable for you depending on the stage of bladder cancer, your symptoms and your overall health. There are many treatment options available which you can read more about below.

How Is Bladder Cancer Treated?

There are different treatment options available based on which stage of bladder cancer you are at.

1. Non-muscle invasive bladder tumour

Transurethral resection of bladder tumour (TURBT) followed by a single dose of post-resection instillation of Bacillus Calmette-Guerin (BCG) in the bladder (intravesical BCG) is the main treatment for superficial (non-muscle invasive) bladder cancers. Sometimes, a second, more extensive TURBT is done to better ensure that all cancer has been removed.

For patients with a high risk of recurrence based on stage, grade, number and size of cancers, a longer course of intravesical BCG is recommended after the surgery. Strict adherence to careful surveillance protocol is important as patients remain at risk of recurrence and progression to muscle-invasive bladder cancer.

Those with recurrent non-muscle invasive bladder cancers may need repeated TURBT with intravesical BCG or surgery (radical cystectomy); depending on the stage, grade and duration since the last dose of intravesical BCG.

Anti PD1/PD-L1 immunotherapy is currently being explored as an alternative to radical cystectomy in BCG-unresponsive non-invasive bladder.

2. Muscle invasive TCC

Surgery is the standard of care for BCG-unresponsive non-muscle invasive bladder cancers and muscle invasive bladder cancers. Radical cystectomy is an operation where the whole bladder and adjacent lymph nodes with prostate (men) or uterus, fallopian tubes and ovaries (women) are removed.

After the bladder is removed, reconstructive surgery is done to allow urine to be stored and drained out. Usually, draining ureters from the kidneys are connected to a refashioned short segment of the intestine that acts as a urine pouch. One end of the refashioned urine pouch is connected to the abdomen skin where urine can flow out.

Radical cystectomy is a major surgery and not all patients will want to do it or are medically fit for it. Bladder preservation strategy using a combination of TURBT followed by chemotherapy and radiotherapy is an alternative in a minority of patients.

Most patients with muscle-invasive bladder cancers will be recommended to have neoadjuvant chemotherapy (chemotherapy prior to surgery). Administration of cisplatin-containing combination chemotherapy prior to surgery reduces recurrence and improves survival in muscle invasive bladder cancers. Kidney function needs to be preserved for the safe use of cisplatin. Patients with swollen kidney(s) from bladder cancer compressing on ureter(s) will need to have the obstruction relieved. Following surgery, further adjuvant treatment with Nivolumab (anti PD1 immunotherapy) improves disease-free survival by 30% for patients with high-risk muscle-invasive bladder cancer, based on CHECKMATE 274 study.

3. Metastatic TCC

The first line of treatment for metastatic bladder cancer remains combination chemotherapy containing cisplatin in patients who are suitable to receive cisplatin.

For cisplatin-ineligible patients, anti PD1/PDL1 immunotherapy is an alternative in patients with tumours that are positive for PD-L1 expression. The role of anti PD1/PDL1 immunotherapy has also been defined in maintenance treatment after initial cisplatin-containing chemotherapy and in patients who have progressed after cisplatin-based chemotherapy.

On top of immunotherapy, additional promising progress in the treatment of metastatic bladder cancer has been made in the form of targeted therapies. These treatments work by blocking specific proteins/mutations found in cancer cells. Fibroblast growth factor receptors (FGFR) inhibitor, Erdafitinib, has shown activity in patients who progressed after chemotherapy and have FGFR2 or FGFR3 mutations identified in the tumour. Enfortumab vedotin is an antibody that targets cell adhesion molecule nectin-4 commonly found on the cell surface of bladder cancers. The ideal sequence and combination of drugs for metastatic bladder cancer is actively being explored in clinical trials.

Conclusion

In a nutshell, TCC is the most common type of bladder cancer and is often associated with cigarette smoking. Non-muscle invasive bladder cancer is managed by local resection (TURBT). High-risk cases will benefit from a course of BCG administered into the bladder. For muscle-invasive bladder cancer, management typically involves the administration of cisplatin-based chemotherapy prior to definitive surgery to remove the whole bladder.

In a carefully selected group of patients, a bladder-preserving approach may be appropriate using a combination of TURBT, chemotherapy and radiation therapy. Cisplatin-based combination chemotherapy remains the cornerstone treatment for metastatic TCC. However, new drug discoveries in the form of immunotherapy and targeted therapy have greatly expanded the treatment armamentarium for this disease.