Bladder cancer treatment in Germany

In the overwhelming majority of cases, bladder cancer is a transitional cell (urothelial) carcinoma. Patients report haematuria or urinary urgency (increased frequency and/or an urgent need to urinate). As the symptoms progress, further obstruction of the urinary tract may cause pain. Diagnosis is made by cystoscopy and tumour biopsy.

Treatment consists of:

• fulguration;
• transurethral resection;
• intravesical instillations;
• radical surgery;
• chemotherapy or a combination of these methods.

Bladder cancer is the 4th most common cancer in men and is less common in women; the male-to-female ratio is about 3:1. Bladder cancer occurs more often in white people than in African Americans, and its incidence increases with age.

Types of bladder cancer include:

• transitional cell carcinoma (urothelial carcinoma), which accounts for more than 90% of all cases (most tumours are papillary, tend to be superficial, well differentiated and exophytic; flat tumours are more insidious and prone to earlier invasion and metastasis);
• squamous cell carcinoma, which is less common and usually occurs in patients with parasitic infestation of the bladder or chronic irritation of the mucosa;
• adenocarcinoma, which may be a primary tumour or, in rarer cases, a metastasis of bowel cancer; metastatic disease must be ruled out.

In more than 40% of patients, tumours recur at the same or another site of the bladder mucosa, especially if the tumours are large, poorly differentiated or multifocal. Bladder cancer usually metastasises to the lymph nodes, lungs, liver and bones. Expression of mutations of the p53 tumour gene may be associated with tumour progression.

Carcinoma in situ of the bladder is high-grade but non-invasive and usually multifocal, and it is prone to recurrence.

Clinical presentation

In most patients the disease presents with haematuria without any apparent cause. In some patients it begins with anaemia, and the haematuria is found during the work-up. The onset of the disease also typically involves urinary symptoms (dysuria, burning, pollakiuria / increased urinary frequency) and pyuria / pus in the urine. Pelvic pain occurs at the late stages of the cancer, when a pelvic mass can already be clearly palpated.

Diagnosis

• cystoscopy with biopsy;
• urine cytology.

Bladder cancer can usually be suspected clinically with the help of urine cytology, which sometimes reveals malignant cells. Cystoscopy and biopsy of any abnormal areas are performed first, since these examinations are necessary even if urine cytology is negative. Urinary antigen assays are not recommended for routine diagnosis. They are used when cancer is suspected but cytology results are negative.

At the early stages of the disease (stage T1 or more superficial tumours), which account for up to 70–80% of cases, cystoscopy with biopsy is sufficient for staging. However, if the biopsy shows a tumour that is more invasive than a superficial flat lesion, an additional biopsy is indicated, including a biopsy of muscle tissue. If muscle invasion is found (stage T2 and above), CT of the abdomen and pelvis and a chest X-ray are ordered to determine the local extent of the tumour and rule out metastases. Patients with invasive tumours undergo a bimanual examination (digital rectal examination in men, rectovaginal examination in women) under anaesthesia during cystoscopy with biopsy. The standard TNM staging system (tumour, nodes, metastases) is used.

Treatment

• transurethral resection (TUR) of the tumour and intravesical therapy (for superficial cancer);
• cystectomy (for invasive cancer);
• superficial cancer.

Superficial tumours can be completely removed by transurethral resection or coagulation. A course of chemotherapy, for example mitomycin C, can reduce the risk of recurrence. In carcinoma in situ and other poorly differentiated superficial transitional cell tumours, immunotherapy (for example, with intravesical bacillus Calmette-Guérin / BCG) after transurethral resection is usually more effective than instillations of chemotherapy drugs. Instillations may be given at intervals ranging from once a week to once a month for 1−2 years.

Invasive cancer

Tumours that grow into the muscle layer of the bladder wall (i.e. stage T2 and above) usually require radical cystectomy (complete removal of the bladder and the adjacent organs) with subsequent urinary diversion; bladder resection is possible in fewer than 5% of patients. In patients with locally advanced tumours, cystectomy is increasingly performed after neoadjuvant chemotherapy. Extended lymphadenectomy during surgery may improve survival. Urinary diversion usually involves rerouting the urine through an ileal conduit to a urostomy on the surface of the abdomen and collecting it in an external urine bag. Alternative techniques, such as creation of an orthotopic neobladder or urinary diversion with a cutaneous stoma, are becoming more common and are suitable for many patients. In both cases an internal reservoir is created from a segment of small bowel. In the case of an orthotopic neobladder, the reservoir is connected to the urethra. Patients empty the reservoir by relaxing the pelvic muscles and increasing intra-abdominal pressure so that the urine passes through the urethra in the most natural way. Most patients are continent during the day, but some incontinence may occur at night. With continent diversion techniques, the reservoir is connected to a continent stoma on the abdominal wall. Patients empty the reservoir by self-catheterisation at regular intervals during the day.

Protocols that combine chemotherapy and radiotherapy make it possible to preserve the bladder and may be intended for some elderly patients or for those who decline radical surgery. These protocols can provide a 5-year survival rate of 20–40%.

Patients must be re-examined every 3–6 months for progression or recurrence of the disease.

Metastatic or recurrent cancer

Metastatic tumours require chemotherapy, which is often effective but rarely leads to a cure, except when the metastases are confined to the lymph nodes. Combination chemotherapy can prolong the lives of patients with metastatic tumours.

Treatment of recurrent cancer depends on the clinical stage, the site of the recurrence and the previous treatment. Recurrence after transurethral resection of superficial tumours is usually treated by repeat resection or coagulation.