Bladder carcinoma is a malignant disease of the bladder. In most cases the tumour arises from the urothelium, the inner lining of the urinary tract – this specialised tissue is also found in the renal pelvis, the ureters and parts of the urethra, so urothelial carcinomas can in principle occur anywhere in the urinary tract, though the bladder is affected most often. In Switzerland, around 1,400 people develop bladder cancer every year, and around 600 die from it each year. About 70% of those affected are men, and the risk of the disease increases markedly with age – most patients are over 70 years old at the time of diagnosis.
Risk factors: why smoking harms the bladder
The bladder stores the urine produced by the kidneys for several hours. Carcinogenic substances that are absorbed, for example, through the lungs and then excreted via the kidneys can therefore act on the bladder lining for a long time in concentrated form. The most important avoidable risk factor is smoking, which contributes to around half of all bladder carcinomas. Quitting smoking is still worthwhile even after a cancer diagnosis: continued smoking is associated with a higher risk of recurrence, disease progression and tumour-related mortality.
Other possible risk factors include long-term occupational exposure to aromatic amines (for example in certain areas of the dye, rubber, metal or chemical industries), previous radiotherapy or certain chemotherapies in the pelvic area, chronic bladder irritation from long-term indwelling catheters, and — in endemic areas — infection with the parasite Schistosoma haematobium (schistosomiasis). Chronic irritation and schistosomiasis are particularly associated with squamous cell carcinoma of the bladder, which is rare in Europe.
Key warning sign: visible blood in the urine
The most common warning sign is visible blood in the urine, particularly when it is painless and the urine appears pink, red or dark brown. Even if the blood appears only once and then disappears completely, it should be assessed by a urologist promptly: haematuria often has benign causes such as a urinary tract infection, urinary stones or an enlarged prostate, but a tumour of the urinary tract must be reliably ruled out.
Less commonly, symptoms such as frequent or suddenly urgent need to urinate, burning or pain when urinating, recurring apparent urinary tract infections, or unclear pain in the lower abdomen or flank can occur. In particular, a flat carcinoma in situ (CIS) can cause pronounced irritative symptoms without being immediately visible on imaging.
Diagnosis and initial treatment
The most important examination is flexible cystoscopy: a thin, flexible instrument is passed under local anaesthesia through the urethra into the bladder. The examination usually takes only a few minutes and can be carried out on an outpatient basis in our practice. Depending on the individual situation, additional tests such as a urine test and culture, urine cytology, an ultrasound of the kidneys and bladder, CT urography or, for invasive tumours, further cross-sectional imaging to assess lymph nodes and possible metastases may be needed.
If cystoscopy reveals a suspicious finding, a transurethral resection of the bladder (TURBT) is usually performed under general or regional anaesthesia: the tumour is removed via the urethra and then examined histologically. The tissue analysis reveals not only the type of tumour, but also how aggressive the tumour cells appear, how deeply the tumour has invaded the bladder wall, and whether the bladder muscle is affected. In certain findings, a second resection is required after a few weeks to rule out any remaining tumour tissue and more reliably assess the depth of invasion.
Early instillation. For a presumably superficial tumour with a low or selected intermediate risk of recurrence, a drug such as mitomycin can be instilled into the bladder once, immediately after TURBT, to destroy free-floating or remaining tumour cells. This is only done if there are no signs of bladder injury, significant bleeding or other contraindications.
Treatment by tumour stage: non-muscle-invasive or muscle-invasive
Further treatment depends crucially on whether the tumour has reached the muscle layer of the bladder.
Non-muscle-invasive bladder cancer (NMIBC). About three-quarters of bladder carcinomas are diagnosed at this stage, where the tumour is confined to the lining or the underlying connective tissue layer. Further treatment depends on the individual risk of recurrence and progression: for low risk, regular follow-up may be sufficient after complete TURBT and, if applicable, early instillation. For intermediate risk, repeated drug instillations — intravesical chemotherapy or BCG treatment, depending on the individual risk profile — may be appropriate. For aggressive tumours, carcinoma in situ, or high-grade T1 stage, we generally recommend BCG therapy followed by maintenance treatment; for a particularly high risk of progression, early removal of the bladder must also be discussed.
What is BCG therapy? BCG (Bacillus Calmette-Guérin) is a weakened bacterial strain originally developed as a live vaccine against tuberculosis. In bladder cancer, however, it is not given as a vaccination but as a local immunotherapy instilled directly into the bladder via a thin catheter: contact with BCG triggers a targeted immune reaction in the bladder lining against any remaining tumour cells. Treatment usually begins with six weekly instillations, followed by maintenance therapy for one to three years. Temporary symptoms such as frequent urination, burning when urinating, blood in the urine or flu-like symptoms can occur, which is why we closely accompany and monitor the treatment.
Muscle-invasive bladder cancer (MIBC). If the tumour has invaded the muscle layer of the bladder wall, there is a higher risk that the disease will spread beyond the bladder. Treatment is planned individually and requires close cooperation between urology, medical oncology, radiology, radiation oncology and pathology; we present affected patients at the uro-oncology tumour board at Lucerne Cantonal Hospital. For patients suitable for cisplatin-based chemotherapy and immunotherapy, current European guidelines recommend perioperative chemo-immunotherapy: before radical removal of the bladder, a combination of gemcitabine and cisplatin is given together with the immune checkpoint inhibitor durvalumab; after surgery, treatment with durvalumab continues for a limited period. The aim is to shrink the tumour before surgery, tackle non-visible micrometastases early, thereby reducing the risk of later recurrence and improving long-term chances of a cure. Whether this treatment is an option depends, among other things, on kidney function, general health, any coexisting conditions and individual contraindications to immunotherapy.
This treatment concept is based on the international randomised phase III NIAGARA trial in more than 1,000 patients with muscle-invasive bladder cancer: after two years, around 68% of those treated with durvalumab were free of a defined disease event, compared with around 60% under the previous standard treatment; overall survival was also improved, at around 82% versus around 75%.
In radical cystectomy, the bladder and the associated pelvic lymph nodes are removed surgically, after which a new form of urinary diversion must be created. Depending on age, general health, kidney function, previous surgery and personal preferences, options include an ileal conduit (urine is diverted via a short segment of small bowel to an opening on the abdominal skin, collected in a bag), an orthotopic neobladder (a new urine reservoir formed from small bowel and connected to the urethra), or other continent or internal diversion procedures; the advantages and disadvantages of the various methods are discussed in detail and individually before surgery.
In carefully selected patients, trimodal bladder-preserving therapy — consisting of as complete a TURBT as possible, radiotherapy of the bladder, and concurrent chemotherapy to enhance the effect of the radiation — can be a curative alternative to bladder removal. Requirements include a suitable tumour situation, an adequately functioning bladder, and willingness to undergo close, long-term follow-up; if the tumour does not fully respond to treatment or recurs, later removal of the bladder may become necessary.
Follow-up care
Urothelial carcinomas can recur in the bladder or elsewhere in the urinary tract, so structured follow-up care is an essential part of treatment. Depending on tumour stage and risk group, this includes regular flexible cystoscopies, urine cytology, ultrasound and cross-sectional imaging, kidney function checks, examinations of the upper urinary tract if needed, and counselling and support to stop smoking. We adapt the intervals between check-ups individually to the risk of recurrence and progression.
A diagnosis of bladder cancer raises many questions for those affected and their families. We support our patients through every phase of the disease — from the initial assessment through treatment planning to long-term follow-up — and coordinate care at a hospital or specialist centre where needed, to ensure a seamless flow of information between all the disciplines involved.