Bladder Cancer

Who Should Be Investigated?

Epidemiology

In Europe, 110,500 cases of bladder cancer were diagnosed in 20081 and an estimated 70,530 will be diagnosed in the USA in 2010,2 making it the fourth most common cancer in men and twelfth most common cancer in women. The incidence is around three to four times higher among men than women and two times higher among white than black populations.3 It has been demonstrated that bladder cancer is one of the most expensive cancers in terms of lifetime costs per patient, mainly due to the lifelong need for follow-up and high recurrence rates in nonmuscle-invasive disease requiring multiple treatments.4

Risk Factors

Several risk factors for bladder cancer have been identified. Cigarette smoking is the most important risk factor, resulting in a twoto fourfold increased risk for bladder cancer. Although cessation of smoking reduces the risk, the risk level will always remain higher compared to nonsmoker.5 Occupational exposure to urothelial carcinogens is another important risk factor. Workers in the chemical, dye, and rubber industries (aromatic amines) or aluminum, coal, and roofing industries (polycyclic aromatic hydrocarbons) have an increased risk of developing

bladder cancer, as well as painters and hairdressers.5 Furthermore, exposure to pelvic radiotherapy or antecedent treatment with cyclophosphamide, a drug used in the management of lymphoproliferative and myeloproliferative diseases, increases the risk for bladder cancer.5 This risk is proportional to the duration of exposure or received dose. Consumption of coffee or artificial sweeteners has been suggested as risk factor; however, this has never been confirmed in large series.5 While the aforementioned risk factors may lead to the development of urothelial cell carcinomas (UCC), chronic urinary tract infection (e.g., due to indwelling bladder catheter) and Schistosomiasis infection are both associated with an increased risk of developing squamous cell carcinoma of the bladder.6 Schistosomiasis (also known as bilharziasis) is a parasitic disease which is highly endemic in Egypt, but also to a lesser degree in other parts of Africa, in the Middle East, the Caribbean, South America, and East Asia. The eggs of S. haematobium cause a chronic inflammatory response, resulting in changes in the urothelium that may ultimately lead to a squamous cell carcinoma. The time between onset of schistosomiasis infection and subsequent development of squamous cell carcinoma is around 30 years.7

Of all bladder cancers, UCC is the most common subtype (>90%). Squamous cell carcinoma and adenocarcinoma account for 5% and 1% of bladder cancers, respectively.Very rare subtypes of bladder cancer are small cell carcinoma, sarcoma, and metastases.5

BladdEr cancEr

Figure 37.1. Example of a bladder diagram and documentation of a papillary bladder tumor (ptag2) with indication of the anatomic location.

d

x

R

c L

e

b

a

a= Trigone

b= Posterior wall

c= Dome

d= Anterior wall

e= Right lateral wall f = Left lateral wall

developed to improve the diagnostic accuracy of cystoscopy.Photodynamic diagnosis (PDD),also referred to as fluorescence cystoscopy, is a cystoscopic technique using fluorescence to indicate malignant bladder tissue based on differences in fluorescent capacities between benign and malignant bladder tissue. Prior to cystoscopy, a fluorescent agent is administered intravesically, and when illuminating the bladder wall with light of a specific wavelength (blue light), malignant tissue appears pink/red on a blue background. Several studies have shown that PDD outperforms white light cystoscopy when it comes to sensitivity,especially for CIS.11 However, the relatively low specificity of this technique and the costs remains a problem. Another more recently developed technique is Narrow Band Imaging (NBI). This technique uses light of narrow wavelengths with center wavelengths in the blue and green spectrum of light to enhance contrast of mucosal surface and microvascular structures without the use of dyes. Only two studies in bladder cancer have been published to date.12,13 It has some advantages over PDD (e.g., it is immediately applicable, does not cause any side effects, is not restricted in time by photobleaching, and avoids the extra costs of an intravesical agent), but its clinical applicability has to be established in larger series.

During cystoscopy, no information on histopathological diagnosis is obtained, which makes discrimination of inflammatory lesions and CIS often difficult, since they both can present as

mucosal red spots. Furthermore, estimation of the grade or stage of a bladder tumor at cystoscopy, even by an experienced urologist, is often not accurate. Therefore, new techniques like Raman spectroscopy and Optical Coherence Tomography (OCT) have been developed that aim at providing an objective histopathological diagnosis during cystoscopy in a minimally invasive way. While Raman spectroscopy can estimate the molecular composition of tissue, OCT can produce cross-sectional images with high resolutions comparable to histopathology.14 Both methods show promising preliminary results, but more research still has to be conducted before any of the techniques can be implemented in the management of bladder cancer.

Urine Tests

Urinalysis can detect microscopic hematuria, which is most often defined as more than three erythrocytes per high-power field.Since hematuria can be intermittent, repeat testing increases the chance to find hematuria. No clear correlation is found between the degree of hematuria and the aggressiveness of the disease.

Urinary cytology is based on a pathologist’s interpretation of morphological changes of urothelial cells. It is an important tool for detection and follow-up of bladder cancer and can be performed on freshly voided urine or on a

What Is the Primary Treatment

in Case a Bladder Tumor

Is Detected?

TUR

Transurethral resection (TUR) is the primary treatment for bladder tumors and has both a diagnostic and therapeutic objective: to obtain tissue for histopathological diagnosis and to completely remove all visible tumors.TUR starts

PDD-Assisted TUR

As mentioned in the previous section, small or flat bladder tumors may be missed during white light cystoscopy, leading to early “recurrences.” Using PDD during TUR can be helpful in accomplishing a more complete tumor resection and prevent overlooking tumors. This was investigated in prospective, randomized studies by comparing the residual tumor rate at repeat-TUR 6 weeks after the initial TUR with white light only versus PDD-assisted TUR. All studies showed a statistically significant lower residual tumor rate