Bladder cancer

 

Bladder cancer is the 2nd most frequent malignancy of the urinary tract after prostate cancer.1 The most common type of bladder cancer, responsible for 90 to 95% of all bladder tumours, is urothelial or transitional cell carcinoma, a cancer that begins in urothelial cells that normally make up the inner lining of the bladder.2

For treatment and prognosis purposes, bladder cancers are classified as:

  • Non-muscle-invasive bladder cancer (NMIBC): Cancer is confined to the bladder mucosa (urothelium, lamina propria) and has not infiltrated the muscular wall. 70% of BC cases are NMIBC at diagnosis. NMIBC includes the subtypes Ta (70%), T1 (20%), CIS (10%)3.
  • Muscle-invasive bladder cancer (MIBC): Cancer has invaded the muscular wall of the bladder and/or spread to nearby organs and/or lymph nodes. 30% of BC cases are MIBC at diagnosis (T2 to T4).

Epidemiology

The bladder cancer is the :
* 4th most frequent cancer in men and 9th most frequent cancer in women in developed countries4
* 5th most common cancer in men and 12th most common cancer in women worldwide.4

The incidence (ASR, age standardized rate) of bladder cancer is estimated as follows:

* 16.7/100,000 (men), 3.2/100,000 (women) in Europe4
* 20.0/100,000 (men), 3.7/100,000 (women) in Northern America4

In most European countries, incidence rates vary between 14 and 21/100,000 in men.

The prevalence of bladder cancer is the highest for all urologic malignancies.5

5-year prevalence in Europe: 116.5/100,000 (men), 29.0/100,000 (women)

Differences in prevalence between countries are caused by differences in registration or reporting of non-invasive versus invasive tumours. This makes the comparison between countries difficult.7

The mortality of non muscle-invasive bladder cancer

is mainly determined by progression rates of high-risk non-muscle-invasive bladder cancer.8,9 Worldwide approximately 145,000 patients die from bladder cancer annually.7

In 2008, bladder cancer was the 8th most common cause of cancer-specific mortality in Europe. 5-year-survival rates for non-invasive cancer is 96% but decreases to 70% once the cancer has spread, and decreases further down to 5.5% in metastatic disease.10

Main risk factors

* The main risk factor is smoking.5
* Professional exposure to carcinogenic substances such as aromatic amines and polycyclic aromatic hydrocarbons (e.g. in dyes, solvents, paints, combustion products, rubber, and textiles)11
* The risk of developing bladder cancer increases with age. The median age at diagnosis is around 70 years12,13

Other risk factors

* Chronic urinary tract infection14
* Schistosomiasis5
* Medications, radiation to pelvic area5

 Symptoms

* The main symptom for NMIBC is painless haematuria.8
* In patients with CIS, haematuria may be accompanied by irritative voiding symptoms like urinary frequency, urgency, dysuria.
* Physical examination does not reveal NMIBC.
* Other symptoms like flank pain (ureteral obstruction), lower extremity oedema, palpable pelvic mass, weight loss and abdominal or bone pain may occur in MIBC or metastatic disease13.

Diagnosis

If bladder cancer is suspected, non-invasive examination methods will be performed initially9:
* Urinary cytology (voided or bladder wash): high specificity in high-grade tumours, moderate sensitivity.15
* Urine biomarkers are being evaluated extensively but to date, there is no consensus regarding their use for the diagnosis of bladder cancer.13
* Voided urine cytology or urinary markers are advocated to predict high-grade tumour before TURB.8
* Imaging examinations:
- Conventional intravenous or computed tomography urography (x-ray examination with contrast agent)
- Ultrasonography (can show tissue changes, tumours, hydronephrosis)

The diagnosis of bladder cancer is made by
* cystoscopic examination of the bladder including (an invasive examination method) biopsies
* histological evaluation of the resected tissue

Treatment

Transurethral resection of bladder tumours (TURB) is the standard surgical procedure for NMIBC. This procedure removes all visible tumours. It has been confirmed that the use of  blue light-guided cystoscopy as an adjunct to white light cystoscopy and TURB is more sensitive than conventional procedures for detection of malignant tumours, particularly for CIS.


Detection of CIS with white light on the left and  blue light cystoscopy on the right
Source: Dr Dirk Zaak, Munich, Germany 

A complete TURB including accurately analysed biopsies allows correct determination of clinically important risk factors for recurrence and progression – it is the initial and crucial step in the management of non-muscle-invasive bladder cancer.9

Additional post-operative treatment of NMIBC includes instillation of chemotherapy or immunotherapy using BCG, combined with frequent monitoring. Radical cystectomy may be proposed.9 The treatment for patients with muscle-invasive bladder cancer includes radical cystectomy.

 


References

1 Pezaro C et al., Urothelial Cancers: using biology to improve outcomes; Expert Review of Anticancer Therapy; 2012; 12(1):87-98.
2 Messing EM, Urothelial tumors of the urinary tract; Campbells Urology 2002; 8:2732-2784.
3 Hendriksen K and Witjes JA, Treatment of Intermediate-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC); European Urology, Supplements 2007; 6:800-808.
4 Ferlay J et al., GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10, available from: http://globocan.iarc.fr, accessed on 09/01/2013.
5 Burger M et al., Epidemiology and Risk Factors of Urothelial Bladder Cancer; European Urology Supplements 2013; 63(2):234-241.
6 Bray F et al., Global estimates of cancer prevalence for 27 sites in the adult population in 2008; International Journal of Cancer 2013; 132(5):1133-1145.
7 Ploeg M et al., The present and future burden of urinary bladder cancer in the world; World Journal of Urology 2009; 27(3):289-293.
8 ICUD 2012.
9EAU Guidelines 2013.
10  http://seer.cancer.gov/statfacts/html/urinb.html, accessed 25/07/2013.
11 Brown T et al., Occupational Cancer in Britain; British Journal of Cancer 2012; 107(S1): S76-S84.
12 Barocas DA et al., Surveillance and Treatment of Non-Muscle-Invasive Bladder Cancer in the USA; Advances in Urology 2012; 2012:421709.
13 IUCD 2004.
14 Kantor AF et al., Urinary tract infection and risk of bladder cancer; American Journal of Epidemiology 1984; 119(4):510-515.
15 Mowatt G et al., Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer; Health Technology Assessment 2010; 14(4):1-331.

Updated on 26 July 2013