/The symptoms, diagnosis and treatment of bladder cancer

The symptoms, diagnosis and treatment of bladder cancer

The symptoms, diagnosis and treatment of bladder cancer 2018-02-27T14:18:07+00:00

Summary

Bladder cancer forms in the cells that line the inner wall of the urinary bladder (the organ that stores urine).

CT Scan showing cancer (arrowed) growing from bladder wall

The incidence in the UK is approximately 11,000 new cases per year, most of these being early cases of the disease that is controlled by local therapies performed at cystoscopy (where the doctor looks inside the bladder and treats the cancer under direct vision). In early stages of the disease, this cure is the ‘norm’, but even for more advanced cases the survival rates are improving.

Most bladder cancers are transitional cell carcinomas (cancer that begins in so-called transitional cells that normally make up the inner lining of the bladder). Other types include squamous cell carcinoma (cancer that begins in thin, flat cells that  have changed from the transitional cells that normally line the bladder – perhaps following chronic irritation of the bladder by chemicals or infections such as schistosomiasis) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids).

In the UK, the disease is found predominantly in older men and often with other medical problems. This can be a potential problem for the oncologist should the patient require treatment other than straightforward local cystoscopic therapy.

Causes

Environmental factors are undoubtedly related to the incidence of the disease with smoking causing a two to six fold rise in the risk of the disease.  It is thought that the aromatic amines in the tobacco smoke are the carcinogenic (cancer causing) agents. They are absorbed into the blood after inhalation into the lungs and then excreted in the urine, where the contact with the bladder wall lining (epithelium) proves the trigger for the eventual development of the cancer.

Workers in industries that involve working with aromatic amines also have a higher incidence of the disease, again due the exposure to aromatic amines (particularly the rubber industry and those workers exposed to dye stuffs).

Interestingly, recent data suggest a familial tendency to the disease and it is thought that the genetic expression of genes that metabolise the toxic substances varies between individuals and hence the excretion/concentration of carcinogenic metabolites in the urine.

In countries where the infectious disease, schistosomiasis is common e.g. Egypt, there is an increased incidence of squamous cancer of the bladder (a type which is otherwise infrequent in the UK).

Incidence

Malignant bladder tumour indenting the radioopaque dye at the base = black indentations into the bladder (left panel) and after treatment (right panel)

Cancer of the bladder is a relatively common cancer. It tends to occur in later life with a male preponderance and presents (usually) by blood in the urine (haematuria). The first investigation is cystoscopy (a procedure where the doctor looks into the bladder through the urethra, nowadays with a fibre optic scope) which allows the visualisation of the bladder’s internal lining, from which all bladder cancers arise.

Early bladder cancer may appear as a polyp that can be fully resected (cut out or burnt with diathermy- heat). Early stages of the cancer may require no other therapy other than repeated cystoscopies over time to check that the tumour has not recurred or new ones arisen.

There are 11,000 cases of bladder cancer diagnosed in the UK annually and most are of the early form just described. However, ultimately, the death rate from this disease in the UK is approximately 5,000 per year (and in the USA 11,000 per year) emphasising that this disease is an important health hazard.

Symptoms & diagnosis: bladder cancer

CT scan demonstrating a bladder cancer as a ‘filling defect’ in the bladder (arrowed).

The classic presenting symptom to the doctor is blood in the urine (haematuria) or occasionally symptoms of bladder discomfort. In particular, haematuria is a symptom that is noticed very early by patients and usually brings them soon to the doctor; at this time, the disease is usually in an ‘early stage’.

However, sometimes, the symptoms referable to the bladder may not occur and then the patient may not present to the doctor until he/ she develops obstructed ureters (due to the tumours blocking the junction here the ureters lead into the bladder) or even until the disease has spread to other organs e.g. liver, lungs or bones.

Diagnosis

CT scan demonstrating a bladder cancer as a ‘filling defect’ in the bladder (arrowed).

In the investigation of blood in the urine, the doctor images the whole of the urinary tubes and passages. An intravenous urogram is performed first, as this will show obvious intraluminal disease at one or more sites (and it is not uncommon for there to be more than one site). The critical diagnostic test (and indeed the first therapy as resection (surgically removed) of all visible disease is performed at the same time) is cystoscopy.

Here, the specialist (urologist) looks into the bladder of the patient and resects (surgically removes) any tumour that he can see, sending the specimens that he resects to the pathology laboratory for examination under the microscope.

Stages

Stages of bladder cancer

In the investigation of blood in the urine, the doctor images the whole of the urinary tubes and passages. An intravenous urogram is performed first, as this will show obvious intraluminal disease at one or more sites (and it is not uncommon for there to be more than one site) and abdomino-pelvic scanning.

The critical diagnostic test (and indeed the first therapy as resection of all visible disease is performed at the same time) is cystoscopy.  Here, the specialist (urologist) looks into the bladder of the patient and resects (surgically removes) any tumour that he can see, sending the specimens that he resects to the pathology laboratory for examination under the microscope.

After resection, the urologist bi-manually feels the bladder to see if there is palpable abnormality (which is a feature of locally invasive/muscle invasive cancers) but, more accurately, he ensures that there is muscle in the deeper biopsies that he performs from the bladder wall tumour.  Based on the pathological/ histological findings, the patient is staged according to the system that is shown in the figure. The earliest stage is where the tumour is confined to the bladder lining and does not invade deep (pT1) and the highest stage (pT4) is where there is invasion of the tumour deep and into adjacent tissues.

Treatment and outcomes: Bladder cancer

Conformal radiotherapy portal for a bladder cancer

Early bladder cancer (e.g. pT1 disease) is treated by the urologist by resection or diathermy, aiming to totally destroy/ surgically excise the entire tumour; this is often possible as the tumour is superficial in the bladder and growing out into the bladder lumen.

After this procedure, and when the pathologist has confirmed that there is no ‘deep invasion’ of the bladder wall, (which implies that there will be disease left behind and further therapy is needed) the urologist will repeat serial follow-up cystoscopies to be sure there is no recurrence at increasing intervals over many years.

Where there is a superficial ‘carpet’ of tumour across the lining of the bladder some instillations of toxic chemicals (e.g. the chemotherapeutic agents, doxorubicin or mitomycin C) or BCG, (the attenuated tubercle bacillus species) into the bladder may be very useful in clearing the disease by causing a chemical ‘burn’.

For more advanced disease (where there is involvement of the bladder muscular wall) where there is no evidence of spread beyond the bladder, then there are several curative treatment options:

In the younger and fitter patient, then cystectomy (the removal of the bladder with reconstruction of some substitute conduit for the urine) is the standard and often best treatment.

For the older patient who would not stand this large operation, then radical radiotherapy (an external beam course lasting 5-6 weeks) is chosen.

Radiotherapy (or chem-radiotherapy – see below) is also chosen when the disease is through the bladder wall and therefore not potentially curable by cystectomy e.g pT4 disease.

Linear accelerator

The modern radiation system is with high energy linear accelerators and using conformal technology/ IMRT. The high radiation dose is carefully ‘moulded’ around the bladder (which is treated empty) as the patient lies on his back on the radiotherapy treatment couch. The treatment takes up to 15 minutes (the majority of this being due to the time taken for the patient to be set-up in the correct position) and the patient feels nothing as the body cannot sense the absorption of this x-radiation. He/she returns the next day (Monday to Friday) for the next treatment (‘fraction’ in radiotherapy parlance).

Many clinical trials are currently in progress as to the optimal way to treat bladder cancer that is invasive. In general, it has been shown that a course of daily radiotherapy lasting over 5-6 weeks is the optimal way to receive curative radiotherapy and the current controversy is over the concurrent use of chemotherapy.

There is no doubt that modern chemotherapy, using drugs such as cis-platinum and gemcitabine can cause a good regression in transitional carcinoma of the bladder and for younger and fitter patients many would now employ it in conjunction with local therapy (surgery or radiotherapy), but frequently in a clinical trial context.

Sometimes, the use of chemotherapy might come first, with one to three courses of chemotherapy used before the radiotherapy to shrink the tumour and hence maybe make it more radiocurable. Sometimes, chemotherapy is used during radiotherapy in an attempt to get synergy between the two modalities of therapy to enhance the cure chance. There is data to support both points of view but the optimal chemotherapy regime and timing of administration are still subjects of controversy and trial data.

Outcomes

Overall, the vast majority of patients with early bladder cancer are in remission after first resection but require careful and prolonged follow-up as there is a chance of both local recurrence and of new tumours developing.

Local relapse in the bladder after conservative therapy (i.e. chemotherapy and radiotherapy) is an indication for the doctor to recommend cystectomy with a high chance of cure.

Once the cancer is muscle invasive (pT3+) the overall chance of cure falls substantially, such that only perhaps 50% of patients will be ultimately cured. This is the main reason that so much effort towards improving results (such as the concomitant use of chemotherapy with radiotherapy) is under trial attention at present.

Where the tumour has spread to other organs, and the bones and later the liver and lungs are at particular risk, is an indication for chemotherapy; however, such chemotherapy is not curative and it use will depend on the patient’s condition, i.e. it may not be recommended for those in particularly poor health. Agents such as cis-platinum and gemcitabine are the best of the chemotherapy armamentarium; their use must be by specialist oncologists, not least because they are toxic, for example to the kidneys. Their supervision and audit of their usefulness needs to made critically.

Screening

Cytology of urine may yield malignant cells as shown here (microscope photo)

It is possible to send urine for cytology. This is where a specialist pathologist looks under the microscope for tumour cells in the urine sediment. This screening test does not have a use on a population wide basis but may have a role in perceived higher risk patients.

Books

The Guide to Living With Bladder Cancer

The Guide to Living With Bladder Cancer Publisher – Johns Hopkins University Press. Bladder cancer is one of the most common cancers and one of the least discussed. In this guide the author, along with the faculty and staff of the Johns Hopkins…