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Cancer of urinary bladder

Most common malignancy of the urinary tract The urinary tract which is made of the kidneys , ureters , the bladder and the urethra – it is lined with transitional cell urothelium from the renal pelvis to the proximal urethra Urothelial ( also called transitional cell carcinoma ) can develop any where along the urinary tract Bladder cancer accounts for about 90 % to 95 % of urothelial carcinoma Most bladder cancers are transitional cell carcinomas ( TCC ) ie the cancer starts in cells called transitional cells in the bladder lining ( urothelium ) Bladder cancer can be seen as a spectrum of diseases from recurrent non-invasive tumours to aggressive or advanced stage disease which needs multimodal and invasive approach It should be noted that WHO has replaced the term TCC with urothelial cell carcinoma and classifies bladder cancer as low grade ( grade 1 and 2 ) or high grade ( grade 3 ) depending upon the degree of nuclear anaplasia and architectural abnormalities Uncommon types of bladder cancers include squamous cell carcinoma , small- cell carcinoma and adenocarcinoma.


Relatively common cancer of the elderly -median age of diagnosis is 72 yrs for men and 75 in women More common in men – 4 fold than in women worldwide Bladder cancer accounts for about 500 000 new cases and 200 000 deaths worldwide Sixth most common cancer in the US and 8th most common cancer in UK Worldwide it is the 7th most common cancer in men In the UK more than 10, 000 new diagnosis of BC is made / year and deaths in excess of 5000 Worldwide it accounts for 3.4 % of the cancer burden Bladder cancer is twice as high in developing countries compared to developed countries.


Terminology / Types of BC – can be complicated , an area of the specialists but it may be important to know certain terms ( it has implications on prognosis , management and therapeutic aims ) as you may 
read them in the letters that you get from the hospital.


As described above 
main types of Bladder cancers are

 Urothelial carcinoma Squamous cell carcinoma Adenocarcinoma Small cell carcinoma Rare types as sarcoma.


Based on morphology the Urothelial or TCCs can 
can be subdivided into Papillary ( papilloma , low malignant potential and papillary carcinoma ) ie are usually non-invasive
 Flat or carcinoma in situ
 ( urothelial carcinoma in situ and invasive )


Non-muscle invasive BC ( NMIBC ) ie the disease is confined to the mucosa ( Ta) or submucosa ( T1 ) , about 75% to 80 % of the initial presentation ( also called superficial )
 Muscle invasive disease ( MIBC ) here the tumour has grown into muscle layer of the bladder or beyond
 Metastatic disease only about 4 % present with metastatic disease which carries a poor prognosis.


Cigarette smoking – most well established risk factor accounting for about 55 % of all cases in the US. Tobacco smoke has aromatic amines & polycyclic aromatic hydrocarbons which are renally excreted.


Advanced age ( average age of diagnosis
 70-84 yrs ) , male sex , white race , personal or family history of bladder cancer ( certain genetic syndromes as Lynch syndrome may also put the individual at higher risk of developing urothelial carcinoma.


Chronic irritation of the urinary tract , infections ( eg Schistosoma hematobium ) , chronic indwelling catheters , obesity , diabetes.


Exposure to ionozing radiation , environmental / occupational exposure to certain drugs , aromatic amines , hydrocarbons , chlorinated hydrocarbons.


Commonly a tumour of older adults , presentation 
can be with microscopic haematuria ( ongoing dilemma )○ also described as non-visible , invisible
○ the definition and description of asymptomatic microscopic haematuria has varied over years
○ how is AMH ( asymptomatic microscopic haematuria ) diagnosed also varies particularly with regard to the role of dipstick urine analysis
○ while gross haematuria is universally recognised as a symptom that should trigger for further evaluation the recommendations for microscopic haematuria and particularly asymptomatic microscopic haematuria ( AMH ) are inconsistent among the available guidelines
○ AUA and ACP define AMH as more than a set number of red cells per high-power filed on microscopy – defined as 3 or more red blood cells per high power field in the absence of infection or proteinuria
○ management of patients with microscopic haematuria can be challenging as 1 in 5 people have microscopic traces of blood in their urine and investigating all patients incurs substantial health care expenditure and investigations are uncomfortable for the patients
○ the decision of undertaking low risk but uncomfortable , inconvenient and expensive tests against the possibility of missing a clinically relevant underlying pathology if the tests were not carried out
○ NICE has not published specific guidance for AMH and NICE guideline does not state whether microscopic haematuria should be diagnosed by urine dipstick or urine microscopy and states that many of the studies investigating the PPV of haematuria do not differentiate between visible and non visible presentations
 gross haematuria ( most common )
relates with advanced disease stage

the risk of bladder cancer is about 4 % in patients with microscopic haemauturia and 16.5 % in those with gross haematuria urinary tract infection ( less commonly ) irritative voiding symptoms upper tract obstruction or pain ( advanced dis ) abdominal pain , loss of appetite or weight incidental finding on imaging

Currently there is no screening available so the diagnosis of BC relies on symptomatic presentation most commonly in primary care.


Benign prostatic hyperplasia Haemorrhagic cyst Prostatitis UTIs Stones Renal cell carcinoma Renal urothelial carcinoma Gynaecological cancer or other pelvic cancers Radiation cystitis Diverticulitis

Adapted from Bladder Cancer by Hatem Kaseb , Narothama R. Aeddula Stat Pearls Continuing Education Activity Jan 2021


Age 45 and above with
 unexplained visible haematuria without UTI or visible haematuria that persists after successful treatment of urinary tract infection

Aged 60 and over and have unexplained non-visible haematuria and either dysuria or a raised white cell count on blood test-refer 2 week usc


Aged 60 and over with recurrent or
 persistent unexplained urinary tract infection- consider non-urgent referral to r/o bladder cancer.


Cystoscopy and urine cytology are valuable investigations in diagnosis and F/U of BC Cystoscopy -a camera roughly 5 mm in diameter is inserted via urethra , allows biopsy , fulguration and or resection Standard white light cystoscopy can miss certain cancers as small papillary tumours or carcinoma in situ -this led to development of newer techniques such as narrow band imaging ( NBI ) and photodynamic diagnosis ( PDD ) Newer techniques improve detection rates of inconspicuous bladder cancer and dyes as 5-ALA can be instilled into the bladder which are absorbed by dysplastic tissue enabling photosensitization Urinary markers –Urine cytology is the most well known and widely used technique , can be done during cystoscopy- it involves a pathologist’s survey of sloughed primarily high grade malignant urothelial cells which loose their adhesive properties more readily than non-malignant cells Various biomarkers are under development and several FDA approved tests are available Urothelial cancers are often multifocal this implies that the entire urothelium needs to be evaluated if a tumour is found CT scan ( eg CT urography ) or MRI of the abdomen and pelvis – anatomic characterization of the lesion and possible delineation of suspected depth of invasion.


Management will be guided by presence or lack of muscle invasion NIMBC -Endoscopic resection and risk based intravesical therapy followed by active surveillance , urine cytology screening and / or adjunctive molecular screening Complete transurethral resection of the bladder is diagnostic and potentially therapeutic and allows to perform disease staging TURBT is effective and essential diagnostic tool but 45 % of patients will suffer a recurrence of tumour within 12 months MIBC based on stage , neoadjuvant therapy followed by, if the patient can tolerate life changing surgery and willing to accept consequences ( radical cystectomy is resection of bladder , adjacent organs and regional lymph nodes ) Radical radiotherapy is also used particularly in the elderly who may have multiple co-morbidities.


Recurrence is very common in bladder cancer NMIBC has the highest recurrence rate among solid tumours Recurrence is secondary to various factors as missed tumours , incomplete initial resection , reimplantation of tumour cells after resection and tumour occurrence in high risk urothelium Routine lifelong surveillance is often practiced following a diagnosis


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  8. Diagnosis and Pathology of Bladder Cancer Diagnosis and Pathology of Bladder Cancer (
  9. Asymptomatic Microscopic Haematuria in Women Committee Opinion ACOG Asymptomatic Microscopic Hematuria in Women | ACOG
  10. Guideline of guidelines: asymptomatic microscopic haematuria Brian J. Linder*, Edward J. Bass† , Hugh Mostafid† and Stephen A. Boorjian*
    *Department of Urology, Mayo Clinic, Rochester, MN, USA, and † Department of Urology, Royal Surrey County Hospital,
    Guildford Surrey, UK
  11. Suspected cancer: recognition and referral NICE guideline [NG12]Published:  Last updated: 


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