Analysis Of Bladder Cancer Biology Essay

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Bladder cancer is the seventh most common cancer in the United Kingdom with 10,091 new cases diagnosed in 2007 it ranks the fourth most common cancer in males and eleventh in females. 90% of bladder cancer is transitional cell cancer. Smoking is responsible for about 50% of bladder cancer and other cancers. According to NHS 21% of adults smokes in England. Occupational exposure, drugs used in chemotherapy are risk factors increase the chances of developing bladder cancer. Dipstick urine test used in some private medical centres as screening for haematuria. There is no screening programme for bladder cancer established in the United Kingdom, because the criteria for national screening committee have not been fulfilled.

1.0 Introduction

Bladder cancer is the seventh most common cancer in the United Kingdom. In 2007, about 10,091 new cases of bladder cancer were diagnosed in the United Kingdom. Bladder cancer ranks the fourth most common cancer in males with 7,284 new cases diagnosed and in females it ranks as the eleventh most common cancer with 2,807 new cases diagnosed in year 2007.*

Bladder is a resvoire for urine and its waste product contents. It can be inferred from this that bladder cancer is associated with cumulative exposure to a variety of potentially etiologic carcinogens.*

Bladder cancer can vary from non- series low grade superficial type ''approximately 70%'' to the invasive, aggressive type that can spread and prove to be fatal ''approximately 30%''.*

1.1 Types

About 5% of bladder cancer is accounted for by squamous cell carcinoma. This cancer is usually secondary long term inflammation or bladder infection. Even more rare is adenocarcinoma, which accounts for less than 2% of all bladder cancer.*

1.1.1 Transitional Cell Bladder Cancer (TCC)

TCC is the most common type of bladder cancer. Nearly, all cancers of the bladder start in the layer of cell (transitional cells) which form the linning of the bladder (tranisitional epithelium). These cancers are called transitional cell or urothelial cell cancers.

Bladder cancer may appear as a tumour which has grown into the muscle wall of the bladder, this is known as invasive bladder cancer.

1.1.2 Carcinoma in Situ (CIS)

CIS is a type of early bladder cancer which appears as a red ulcerated area in the bladder. In CIS the cells are very abnormal or high-grade, so it can grow quickly. If not treated efficiently there is a high risk that CIS will become an invasive cancer.

1.1.3 Sqaumous cell Cancer and AdenoCarcinoma

Squamous cell cancer and adenocarcinoma are considered to be rarer type of bladder cancer. Squamous cell cancers start from one of the types of cells in the bladder lining. Adenocarcinoma starts from glandular cells which produce mucous. Usually, both the types are invasive.*

1.2 Risk factors

There are different risk factors which are considered to increase chances of causing bladder cancer.

1.2.1 Older age

Bladder cancer occurs predominantly in older age 50 years old and older with mean age (65 years old)

1.2.2 Sex

Occurs in men about three times more than women with ratio male to female 3:1

1.2.3 Race

Occurs mostly in white race more than black people for unknown reasons

1.2.4 Smoking

In Europe, about two thirds of all cancers in men and about a third in women are caused by smoking. Smoking 'cigarettes or pipes' increase the risk of getting bladder cancer six '6' times more than non-smoker. The chemical in the smoke get into the blood stream, and then they are filtered by the kidney and end up in urine. Some research suggest that exposure to second hand smoke in childhood may increase bladder cancer risk.

1.2.5 Occupational exposure

Aromatic amines are known to cause bladder cancer. These chemicals have been banned in the United Kingdom for about 20 years, but it can take up to 25 for a bladder cancer to develop.

Another group is polycyclic hydrocarbons, which increase the risk of bladder cancer. There are some jobs which have been linked to an increased risk of bladder cancer e.g. Bus driver, Leather workers, Painters, Miners…etc.

1.2.6 Water disinfection chemical

Chlorine is used to disinfect drinking water, washing water and swimming pool. However, it can be break down into chemicals called trihalomethanes (THMs) which have been linked to bladder cancer. Nevertheless, the increase in risk is very low and it is important to rate that disinfecting water reduces the risk of serious infectious diseases.

1.2.7 Treatment for other cancers

Cancers of pelvic area which treated radiotherapy e.g. prostate cancer, kidney cancer can increase the risk of bladder cancer and so the chemotherapy drug like cisplatin affects in the same way.

1.2.8 Diabetes

Men who have diabetes type II have 40% increase in their risk of developing bladder cancer.

1.3 Symptoms

The most common sign for bladder cancer is haematuria- passing blood with the urine-. Other symptoms are usually involved with urination pattern;

Burning sensation while urinating.

Sudden urge to urinate.

Needs to urinate on more frequent basis.

1.4 Diagnosis

Cystoscopy; examining the bladder

X-ray (Intravenous Urography ''IVU''); Special dye is injected for bladder examination.

Ultrasound, MRI scan and CT scan; examining the bladder system

Biopsy; examining tissue of suspected site for any carcinoid change.

2.0 Evaluate bladder cancer screening programme against NSC

Despite the high incidence of bladder cancer cases, there is no screening program for bladder cancer in the United Kingdom. To establish new screening program me National Screening Committee (NSC) criteria should be met, which could be summarised into four major titles Condition, Test, Treatment and Screening program.

In this writing I shall illustrate the reason/obstacles for not starting a screening program for bladder cancer in the United Kingdom from NSC point of view.

2.1 The Condition

2.1.1 The condition must be an important health problem

Despite the high figures which illustrate the number of cases of bladder cancer, however, the number of people developing bladder cancer is low and so is the mortality rate when compared with more common cancer.

In 2008, there were 5,002 deaths from bladder cancer. On the other hand, there were 35,261 deaths from lung cancer and 16,259 deaths from colorectal cancer.

2.1.2 The epidemiology of the condition must be known

Bladder cancer is almost three times more common in male with ratio male to female 3:1. Bladder cancer occurs in adult aged 60+ years old.

There are many risk factors which have identified for increasing the chances of getting bladder cancer. Smoking is responsible for about 50% of bladder cancer-other cancers also- cases. Some products were banned in the UK because of their involvement in developing bladder cancer such as aromatic amines. Drugs which are used for chemotherapy (cisplatin) have been identified as one of the risk factor.

2.1.3 The natural history of the condition must be understood

The most common type of bladder cancer in the UK is transitional cell cancer ''TCC'' -about 90% of bladder cancer- which sub divided into two distinct:

Low grade tumour that frequently recurs.

High grade malignancy which present frequently as an invasive disease.

70-80% of bladder cancer present as early stage, superficial papillary lesion. 20% are initially diagnosed as invasive disease. Superficial tumours have great chance to recurs, and 10-20% progress to bladder wall invasion.

Patients with invasive tumours are at high risk for disease progression, and despite the diffinitive therapy(cystectomy) the overall five years mortality rate is almost 50%.

Haematuria is the most common sign which is presented in about 90% of bladder cancer cases.

2.1.4 There should be a recognised latent period or early symptomatic stage

The majority of bladder cancer (76%) presenting clinically without screening is superficial disease. However it is unlikely that earlier detection would offer any advantage for these cases.

In one study about 95% of bladder cancer cases which were detected through screening for microscopic haematuria is superficial. However there were differences between the screened and non-screened group, including the prevalence of current smoking.

It is acknowledged that a randomised trial would be necessary to confirm the efficacy of bladder cancer screening.

Bladder cancer does not have a long pre-clinical stage, therefore urine testing would need to be carried out frequently in order to be able to detect potentially invasive tumours.

2.1.5 All the cost effective primary prevention interventions should have been implanted as far as practicable

Smoking accounts for about 50% of bladder cancer. About 21% of England adult population smoke cigarettes. About 757,537 people in England set a quit date through NHS stop smoking service in 2009, almost half (49%) of these were abstained in four weeks follow up study after their quitting date. It is predicted that only half of these smokers who have abstinent will still be abstinent at one year.

2.2The Test

2.2.1There should be a simple, precise, safe and validated screening test

In some settings(such as new patient examinations in general practice and insurance medical examinations), urine dip testing for small quantities of blood in asymptomatic microscopic haematuria (AMH) is used as screening test for urological and kidney conditions including bladder cancer.

A single microscopic haematuria is simple and safe, but screening for AMH requires repeated test- due to intermittent nature of blood loss from urological cancer- which is not safe or simple. The only method that remains to exclude bladder cancer would be cystoscopy, but it requires sedation and carries the risk of infection and bleeding.

The positive predictive value(PPV) of microscopic haematuria for urological cancer is very low especially in patients aged less than 50 years old. Many studies were done to determine the efficiency and validation of microscopic haematuria test through PPV, yet they have not succedded.

In one study, out patients aged 50 and 60 years old (mean age 65) have demonstrated PPV for microscopic haematuria for bladder cancer of 8% and 3% respectively.

In another cross-sectional population study patients who tested positive and negative for microscopic haematuria were followed up to determine risk of urological disease. Urological cancer was found in 1.2% of positive microscopic haematuria patients and 0.2% of negative microscopic haematuria patients. On sub-analysis of urological cancers, prostate cancer was found in significantly higher percentage of those with positive test.

In summary the positive predictive value of microscopic haematuria is low and may not confer a significantly higher risk for bladder cancer than a negative result for microscopic haematuria and for this microscopic haematuria is not considered a valid test for bladder cancer.

2.2.2 The distribution of test values in the target population should be known and a suitable cut-off level defined and agreed

In population surveys the prevalence of asymptomatic microscopic haematuria varies between 0.19% and 21% depending on the age and gender of the population screened and the number of tests performed.

Dipstick test is qualitative test (positive or negative). It is suggested that all positive are followed up by microscopic haematuria(quantitative test). Microscopic haematuria is defined as three or more red blood cells present in urinary sediment (from two of three properly collected urinalysis sediment) per high-powered microscopic field.

The cut-off level is regarded as any amount of microscopic haematuria. Due to the large positive testing patients' number (21%) and low PPV of the test (as mentioned in paragraph 1.5) a large number of patients would need to undergo invasive test like cystoscopy to detect bladder cancer in small number of cases.

2.2.3 The test should be acceptable to the population

Dipstick test is found to be accepted by population in health care services, however it is less acceptable for self-testing at home. Because of the intermittent nature of microscopic haematuria caused by urological tumours, patients have to use self -testing repeatedly which is found unacceptable.

The invasive tests which are recommended after AMH positive result such as cystoscopy and intravenous urography are found to be less acceptable.

2.2.4 There should be an agreed policy on the further diagnostic investigation of individuals with a positive test result and on the choices available to those individuals

The mostly recommended tests as confirmatory for patients who have positive test results of microscopic haematuria are cystoscopy and intravenous urography. However, as discussed above the yield of these investigations is small.

2.2.5 There should be agreed evidence based policies covering which individuals should be offered treatment and the appropriate treatment to be offered

There are agreed evidence based policies for the treatment of the different grades and stages of bladder cancer.

2.3The Treatment

2.3.1There should be an effective treatment or intervention for patients identified through early detection

Survival in patients with bladder cancer is strongly associated with diagnosis stage. Although most cancers are superficial diagnosis, with a 90% 5 year survival, 10-20% have been invaded the bladder muscle when first diagnosed with a 5 year survival of less 50%.

Periodic screening will have a limited potential to detect invasive cancers at an early and more treatable stage.

Some studies have demonstrated that screening can pick up more diseases at a superficial stage and that survival in these cases of bladder cancer is superior. However, these studies suffer from number of bias including lead-time bias, length-time bias and selection bias and no firm conclusion can be stated without randomised trials of screening.

Many intravesical chemotherapeutic agents have been shown to reduce tumours recurrence when used in conjunction with transurethral tumour resection. Unfortunately however, none of these agents have proved to benefit in preventing disease progression.

2.3.2 There should be agreed evidence based policies covering which individuals should be offered treatment and the appropriate treatment to be offered

Systematic evidence based treatment process exist for the various grades and stages of bladder cancer.

2.3.3 Clinical management of the condition and patient outcomes should optimised by all health care providers prior to participation in screening program

In 2001, in more than 32% of bladder cancer cases the diagnosis was made more than 4 weeks after general practitioner (GP) referral with cancer suspicion. For bladder cancer the median time to definitive treatment from GP referral with suspicion of cancer was 47 days (range 1-353)

2.4 The Screening Programme

2.4.1 There should be evidence from high quality randomised controlled trials that the screening programme is effective in reducing mortality or morbidity

This evidence does not exist.

2.4.2 The opportunity cost of the screening programme (including testing, diagnosis and treatment) should be economically balanced in relation to expenditure on medical care as a whole

There is insufficient evidence to suggest that screening programme for bladder cancer would benfit the population. As a result there is no need to consider the cost and cost effectiveness as there is no effectiveness in bladder cancer screening.