Bladder Cancer

Bladder cancer is any of several types of malignancy arising from the epithelial lining (i.e., the urothelium) of the urinary bladder. Rarely the bladder is involved by non-epithelial cancers, such as lymphoma or sarcoma, but these are not ordinarily included in the colloquial term “bladder cancer.” It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer recapitulates the normal histology of the urothelium and is known as transitional cell carcinoma or more properly urothelial cell carcinoma.

Signs and symptoms
Bladder cancer characteristically causes blood in the urine. This blood in the urine may be visible to the naked eye (gross/macroscopichematuria) or detectable only by microscope (microscopic hematuria). Hematuria is the most common symptom in bladder cancer.

Other possible symptoms include pain during urination, frequent urination, or feeling the need to urinate without being able to do so. These signs and symptoms are not specific to bladder cancer, and are also caused by non-cancerous conditions, including prostate infections, over-active bladder and cystitis. There are many other cause of haematuria, such as bladder or ureteric stones, infection, kidney disease, kidney cancers and vascular malformations.

Causes
Tobacco smoking is the main known contributor to urinary bladder cancer; in most populations, smoking is associated with over half of bladder cancer cases in men and one-third of cases among women. There is a linear relationship between smoking and risk, and quitting smoking reduces the risk. Passive smoking has not been proven to be involved.

Diagnosis
Many patients with a history, signs, and symptoms suspicious for bladder cancer are referred to a urologist or other physician trained incystoscopy, a procedure in which a flexible tube bearing a camera and various instruments is introduced into the bladder through theurethra. Suspicious lesions may be biopsied and sent for pathologic analysis.

The gold standard for diagnosing bladder cancer is biopsy obtained during cystoscopy.
A so called cold cup biopsy during an ordinary cystoscopy (rigid or flexible) will not be sufficient for pathological staging either. Hence, a visual detection needs to be followed by transurethral surgery. The procedure is called transurethral resection TUR. Further, bimanual examination should be carried out before and after the TUR to assess whether there is a palpable mass or if the tumor is fixed (“tethered”) to the pelvic wall. The pathological classification obtained by the TUR-procedure, is of fundamental importance for making the appropriate choice of ensuing treatment and/or follow-up routines.

The treatment of bladder cancer depends on how deep the tumor invades into the bladder wall. Superficial tumors (those not entering the muscle layer) can be “shaved off” using an electrocautery device attached to a cystoscope, which in that case is called a resectoscope.

The procedure is called transurethral resection – TUR – and serves primarily for pathological staging. In case of non-muscle invasive bladder cancer the TUR is initself the treatment, but in case of muscle invasive cancer, the procedure is insufficient for final treatment. Immunotherapy in the form of BCG instillation is also used to treat and prevent the recurrence of superficial tumors.

BCG immunotherapy is effective in up to 2/3 of the cases at this stage. Instillations of chemotherapy, such as valrubicin (Valstar) into the bladder can also be used to treat BCG-refractory CIS disease when cystectomy is not an option. Urocidin is phase III trials for this.

Patients whose tumors recurred after treatment with BCG are more difficult to treat. Many physicians recommend Cystectomy for these patients. This recommendation is in accordance with the official guidelines of the European Association of Urologists (EAU) and the American Urological Association (AUA) However, many patients refuse to undergo this life changing operation, and prefer to try novel conservative treatment options before opting to this last radical resort. Device assisted chemotherapy is one such group of novel technologies used to treat superficial bladder cancer. These technologies use different mechanisms to facilitate the absorption and action of a chemotherapy drug instilled directly into the bladder. Another technology uses an electrical current to enhance drug absorption. Another technology, thermotherapy, uses radio-frequency energy to directly heat the bladder wall, which together with chemotherapy shows a synergistic effect, enhancing each other’s capacity to kill tumor cells. This technology was studied by different investigators.

Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (a cystectomy) and the urinary stream is diverted into an isolated bowel loop (called an ileal conduit or Urostomy). In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function, and the site of the disease.

A combination of radiation and chemotherapy can also be used to treat invasive disease. It has not yet been determined how the effectiveness of this form of treatment compares to that of radical ablative surgery.

Photodynamic diagnosis may improve surgical outcome on bladder cancer.

For muscleinvasive urothelial urinary bladder cancer there are a number of treatment options. Gold standard is radical cystectomy as mentioned. In males this usually includes also the removal of the prostate and in females; ovaries, uterus and parts of the vagina. In order to address the problem of micrometastatic disease which initself has implications on longtime survival, new treatment options are dearly needed. Micrometastatic dissemination is often not treatable with only major surgery and the concept of neoadjuvant chemotherapy has evolved. In a number of meta-analyses of randomised prospective trials worldwide, the results have shown survival benefits between 5–8% with this therapy, in a follow up time of 5 years. Thus patients first receive chemotherapy in 3 or 4 cycles, and first after that proceed to major surgery.