History

Fact Explanation
Painless gross haematuria Bladder carcinoma is a common urological cancer. It is more common among males (male : Female ratio of 3:1). The most common type of bladder carcinoma is transitional cell carcinoma. Squamous cell carcinoma and adenocarcinoma are rare. Painless haematuria is the classical symptom of bladder cancer. An adult patient presenting with painless gross haematuria should be considered to have bladder carcinoma until proven otherwise.[1]
Dysuria, frequency, frequent urinary tract infection The tumor mass may cause irritative lower urinary tract symptoms and may predispose to recurrent urinary tract infections.
Sudden onset inability to pass urine and associated severe pain Bleeding from the tumor may lead to formation of clots. These clots may lodge at the bladder neck or urethra and lead to acute urinary retention.
Symptoms due to local spread Chronic pelvic pain may develop due to extravesical spread. Invasion into the ureters may lead to ureteric obstruction. Hydronephrosis may present with loin pain and may be complicated with pyelonephritis.
Symptoms due to regional spread The tumor may invade the regional nerves resulting in pain in the suprapubic region, perineum, inguinal region and may even be referred to the thigh. Involvement of local lymphatics may lead to lower limb swelling.
Symptoms due to distant spread Spread to the liver and lungs is rare. Liver metastases present with right hypochondrial pain, anorexia and jaundice. Metastases of the lung may present with chronic dyspnea, haemoptysis and chest pain.
Risk factors/ aetiological agents Environmental factors play a significant role in bladder cancer. The field change effect describes the same carcinogenic risk along the urinary tract. Smoking is considered a strong risk factor where carcinogens such as nitrosamine and 2-naphthylamine are found in tobacco smoke.[2] Occupational exposure to several organic chemicals and dyes are also linked with bladder cancer - 4-aminobiphenyl, benzidine, chlornaphazine, methylene dianiline etc. Occupations with a higher incidence of bladder cancer include dye workers, textile workers, leather/rubber workers and petroleum product workers.[3] Squamous cell tumors are associated with Bilharzia infection and bladder stones.
References
  1. KAUFMAN DONALD S, SHIPLEY WILLIAM U, FELDMAN ADAM S. Bladder cancer. The Lancet [online] 2009 July, 374(9685):239-249 [viewed 13 August 2014] Available from: doi:10.1016/S0140-6736(09)60491-8
  2. BRENNAN P, BOGILLOT O, CORDIER S, GREISER E, SCHILL W, VINEIS P, LOPEZ-ABENTE G, TZONOU A, CHANG-CLAUDE J, BOLM-AUDORFF U, JöCKEL KH, DONATO F, SERRA C, WAHRENDORF J, HOURS M, T'MANNETJE A, KOGEVINAS M, BOFFETTA P. Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies. Int J Cancer [online] 2000 Apr 15, 86(2):289-94 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10738259
  3. LETAšIOVá S, MEDVE'OVá A, ŠOVčíKOVá A, DUšINSKá M, VOLKOVOVá K, MOSOIU C, BARTONOVá A. Bladder cancer, a review of the environmental risk factors. Environ Health [online] 2012 Jun 28:S11 [viewed 13 August 2014] Available from: doi:10.1186/1476-069X-11-S1-S11

Examination

Fact Explanation
Physical examination is usually normal Early disease usually does not give rise to positive physical findings.
Pelvic mass Advanced disease may rarely form a mass which may be palpable abdominaly or pelvically. On abdominal palpation the mass will be situated in the suprapubic region and will appear arising from the pelvis. The examiner is unable to get beneath the mass. It will be hard, solid in consistency with an irregular surface. Mobility of the mass will be restricted if there is fixation to surrounding structures.
Bimanual palpation : to determine local spread Bimanual palpation via the vagina in females and via the rectum in males may help determine local spread of the tumor. Extension into the anterior vaginal wall in females and to the prostate in males and fixation of the tumor to the surrounding structures can be determined by this approach. The information gathered is used for staging of disease and subsequent planning of management.[1]
References
  1. WIJKSTRöM H, NORMING U, LAGERKVIST M, NILSSON B, NäSLUND I, WIKLUND P. Evaluation of clinical staging before cystectomy in transitional cell bladder carcinoma: a long-term follow-up of 276 consecutive patients. Br J Urol [online] 1998 May, 81(5):686-91 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9634042

Differential Diagnoses

Fact Explanation
Renal Cell Carcinoma Renal cell adenocarcinoma is the commonest tumor of the kidney in adults. The tumor arises from the tubular cells. It is more common among men and the peak age of onset is in the 6th and 7th decades. The most common presentation is with painless haematuria. Blood clots lodged in the ureters may give rise to ureteric colics. A number of patients may present with atypical symptoms. Non specific presentations include pyrexia of unknown origin, constitutional symptoms and anemia. Polycythemia may be present due to ectopic erythropoietin production by the tumor cells. Ectopic hormone production may result in hypercalcaemia, Cushing’s syndrome and virilization. Renal cell carcinoma characteristically tends to grow along the renal vein and into the IVC.[1] This may lead to lower limb swelling and left sided varicocele in males. The tumor characteristically metastasizes to the lungs and bones. Symptoms of the secondaries alone may be the presenting features. The diagnosis is by clinical information aided by imaging of the kidney. Ultrasound scan may show a mass which may be solid or cystic. Intravenous urogram may show the tumor as a filling defect. CT and MRI aid in assessing the degree of local spread.
Bladder stone Bladder is a common site for stone formation. Urinary stasis due to bladder outflow obstruction, urinary infection, bladder diverticulum and foreign bodies predispose to stone formation. Men are more commonly affected. Commonly encountered stone types are oxalate, tri-phosphate and mixed stones. Systemic disorders such as gout and cystinuria may predispose to formation of uric acid stones and cystine respectively. may also occur. Presenting symptoms are frequency, dysuria, sense of incomplete evacuation and recurrent urinary tract infections. The stone obstructing the trigone at the termination micturition causes pain (strangury) and may also cause bright red haematuria. Diagnosis is usually by abdominal X-ray or ultrasound scan. Bladder stones can be managed with Extracorporeal shock wave lithotripsy or surgery.[2]
Hemorrhagic cystitis Hemorrhagic cystitis describes a collection of urinary symptoms occurring due to bladder wall damage. The causative agents include infective – both bacterial & viral, radiation, drugs and chemicals. Pelvic radiotherapy, chemotherapeutic agents and immunosuppressive drugs have clearly being linked with this condition. Hemorrhagic cystitis is a known complication of cyclophosphamide.[3] The insult to the bladder wall leads to inflammation and fibrosis. The common presenting symptoms are frequency, urgency, dysuria, suprapubic discomfort and haematuria. Haematuria may be microscopic or gross even leading to clot formation and clot retention. Physical examination is usually normal. Diagnosis depends mainly on assessment of risk factors. Urine microscopy and cultures are required to exclude an infective cause. Imaging with USS, CT and cystoscopy is often required to investigate haematuria and exclude other organic causes.
References
  1. COHEN HERBERT T., MCGOVERN FRANCIS J.. Renal-Cell Carcinoma. N Engl J Med [online] 2005 December, 353(23):2477-2490 [viewed 13 August 2014] Available from: doi:10.1056/NEJMra043172
  2. HOTIANA MZ, KHAN LA, TALATI J. Extracorporeal shock wave lithotripsy for bladder stones. Br J Urol [online] 1993 Jun, 71(6):692-4 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8343896
  3. STILLWELL TJ, BENSON RC JR. Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients. Cancer [online] 1988 Feb 1, 61(3):451-7 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3338015

Investigations - for Diagnosis

Fact Explanation
Cystourethroscopy This is the first line diagnostic investigation. Cystoscopy is recommended in all patients presenting with haematuria. The bladder and urethra are visualized in a systemic manner. Additional white or blue lighting can be used to detect minimal disease. Studies have shown that blue light hexaminolevulinate cystoscopy significantly improves the detection of bladder cancers.[1]
Intravenous urogram The tumor appears as a filling defect within the bladder lumen. The lumen of the ureters can also be assessed.
Ultrasound scan Ultrasound scan can be used to exclude hydroureter and hydronephrosis. Bladder carcinoma invasion may lead obstruction of the lower end of the ureters leading to proximal dilatation.
Urine : Cytology Urinalysis can detect malignant cells. Presence of malignant cells is specific for bladder cancer. The value of urine cytology as a screening test is limited due to its low sensitivity.[2] In addition to studying cells, new tests are being developed to detect the presence of antigens such as nuclear matrix protein.
References
  1. BURGER M, GROSSMAN HB, DROLLER M, SCHMIDBAUER J, HERMANN G, DRăGOESCU O, RAY E, FRADET Y, KARL A, BURGUéS JP, WITJES JA, STENZL A, JICHLINSKI P, JOCHAM D. Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data. Eur Urol [online] 2013 Nov, 64(5):846-54 [viewed 13 August 2014] Available from: doi:10.1016/j.eururo.2013.03.059
  2. BASSI P, DE MARCO V, DE LISA A, MANCINI M, PINTO F, BERTOLONI R, LONGO F. Non-invasive diagnostic tests for bladder cancer: a review of the literature. Urol Int [online] 2005, 75(3):193-200 [viewed 13 August 2014] Available from: doi:10.1159/000087792

Investigations - Fitness for Management

Fact Explanation
Full blood count To assess the hemoglobin level
Blood urea/ Serum electrolytes To assess renal functions.
Pulmonary function tests Majority of patients are chronic smokers who may have chronic obstructive airway disease. The test will show a restricted type pattern. Pulmonary reserve can be calculated.
ECG/ Echocardiography Assess cardiovascular functions if surgery is considered. Look for evidence of previous myocardial infarction and left ventricular ischemia. Echocardiogram will determine the left ventricular function and ability to withstand surgery. Patients who are unfit for surgery can be determined by these tests and the management of them is discussed in the management section.
References

Investigations - Followup

Fact Explanation
Cystoscopy Regular cystoscopy is required for monitoring of recurrence of malignancy. Even though cystoscopy is considered the gold standard in bladder cancer follow-up, it may miss up to 5% of recurrent disease.[1]
Urine cytology For follow-up of bladder cancer after treatment.
References
  1. AITANEN MP, LEPPILAHTI M, TUHKANEN K, FORSSEL T, NYLUND P, TAMMELA T, FINNBLADDER GROUP. Routine follow-up cystoscopy in detection of recurrence in patients being monitored for bladder cancer. Ann Chir Gynaecol [online] 2001, 90(4):261-5 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11820414

Investigations - Screening/Staging

Fact Explanation
Staging of malignancy Staging of the tumor is based on both clinical examination and investigation findings.[1] Bladder carcinoma is staged into 3 categories - Non-muscle-invasive tumors (pTa and pT1), Muscle-invasive tumors (pT2) and non-invasive primary Carcinoma in Situ.
CT scan Non-contrast CT can be used to assess the local spread of the tumor. Lymph node involvement can also be determined.
MRI MRI is currently being increasingly used for staging of the tumor. MRI is accurate is determining muscle invasion and lymph node involvement.[2]
Chest X-ray To exclude pulmonary metastases.
Bone scan Technetium-99m bone scan should be performed if radical surgery is considered for muscle invasive disease.
References
  1. KIRKALI Z, CHAN T, MANOHARAN M, ALGABA F, BUSCH C, CHENG L, KIEMENEY L, KRIEGMAIR M, MONTIRONI R, MURPHY WM, SESTERHENN IA, TACHIBANA M, WEIDER J. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology [online] 2005 Dec, 66(6 Suppl 1):4-34 [viewed 13 August 2014] Available from: doi:10.1016/j.urology.2005.07.062
  2. BARENTSZ JO, JAGER GJ, WITJES JA, RUIJS JH. Primary staging of urinary bladder carcinoma: the role of MRI and a comparison with CT. Eur Radiol [online] 1996, 6(2):129-33 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8797968

Management - General Measures

Fact Explanation
Patient counseling The diagnosis of bladder cancer should be informed to the patient and family sensitively. Provide information regarding the natural course, aetiology, complications and investigations required in bladder carcinoma. Counsel the patient regarding the stage of disease, treatment options available and prognosis. Patient ideas and wishes should be considered when finalizing the management plan.
Provide psychological support The diagnosis of cancer may cause distress in the patient and family members. Provide adequate psychological support.
Preparation of patient for surgery Majority of patients diagnosed with bladder cancer are elderly male heavy smokers. If radical surgery is contemplated optimize the fitness of the patient. Assess pulmonary functions and cardiovascular functions. Correct anemia if present. Optimize control of blood pressure and blood glucose level in patients with hypertension and diabetes respectively.
Multi-disciplinary care The final management plan should be decided by a team of specialists – surgeon, oncologist, histo-pathologist, urologist, anesthetists, nurses, stoma care therapist etc. Patients should be referred to a stoma care therapist for planning, advising and counseling regarding urinary diversion.[1]
References
  1. DICKSON C. The bladder: cystectomy and ileal conduit to treat cancer. Nurs Times [online] 1995 Oct 18-24, 91(42):34-5 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7479154

Management - Specific Treatments

Fact Explanation
Treatment options Treatment options available to these patients are Endoscopic surgery, radical surgery, radical radiotherapy, neo-adjuvant chemotherapy and immunotherapy - Bacille Calmette–Guérin (BCG).[1] The most appropriate option should be selected depending of the stage of disease, patient fitness and patient desires.
Management of Non-muscle invasive tumors : Endoscopic surgery Endoscopic techniques such as transurethral resection and Holmium laser can be used with equal efficacy.[2] The tumor is excised in layers using a resectoscope. Specimens are collected for histological assessment. Additional layers are resected from the base of the excised mass to determine the level of invasion. Finally the base is coagulated. It is important to ensure complete resection of the mass with adequate marginal resection. Inspect the area surrounding the primary lesion and distant to it. Biopsies are taken from areas suspected to have in-situ carcinoma. Bimanual examination is done to determine the new stage of the tumor. A three way catheter is left in-situ to irrigate the bladder. Bladder perforation is a major complication of this procedure. Meticulous surgical technique is required to prevent perforation.
Management of Non-muscle invasive tumors : Intravesical chemotherapy Following endoscopic resection mitomycin 40mg is instilled into the bladder.[3]
Management of Non-muscle invasive tumors : Follow-up The tumor specimens collected are analyzed to determine the stage and grade of the malignancy. The above mentioned therapy is adequate for low grade pTa disease and patients are followed up with regular cystoscopy. Multiple low to medium grade pTa tumors may require an additional 6-week course of intravesical chemotherapy after endoscopic resection. pT1 tumors are treated with endoscopic resection followed by a repeat resection after 6 weeks, which is followed by intravesical BCG.
Management of Muscle-invasive tumors : Surgery Radical cystectomy and pelvic lymph node dissection is considered the standard treatment for muscle invasive malignancy. Presence of distant metastases must be excluded prior to surgery. The bladder is approached abdominally and is mobilized after ligation and division of blood vessels, supporting ligaments and the urethra. External and internal iliac and the obturator lymph nodes are excised. Surrounding structures such as the uterus, vaginal wall may need to be excised to achieve complete excision of the tumor. Following removal of the bladder alternative drainage of urine is achieved by ileal conduit diversion, continent urinary diversion or orthotopic bladder replacement.[4] Partial cystectomy is currently not used and is reserved for small adenocarcinomas.
Management of Muscle-invasive tumors : Radical radiotherapy External beam radiotherapy over 4-6 weeks is another treatment option for invasive disease. The cure rate of radiotherapy is 40–50%. Hence there is a risk of poor response and recurrence of the tumor. Radiotherapy also carries the risk of chronic inflammation and fibrosis of surrounding structures such as the bladder and rectum.
Management of Muscle-invasive tumors : Neoadjuvant chemotherapy Neoadjuvant chemotherapy prior to radical cystectomy has being shown to improve survival rates.[5] Chemotherapeutic agents used are cisplatin, methotrexate, doxorubicin and vinblastine.
Management of inoperable and metastatic bladder cancer The patient may be unfit for major surgery due to the presence of cormobities, advanced age and renal impairment. Chronic smoking which is a risk factor for bladder cancer can predispose to chronic obstructive pulmonary disease and cardiovascular disease. Radical surgery is ineffective in curing widely metastatic malignancy and is avoided in these patients. These patients are increasingly being treated with novel chemotherapeutic regimes which have equal efficacy while causing less adverse effects. Carboplatin or taxane based therapy and gemcitabine based therapy are such newer regimes. It has being shown to improve survival rates but requires further evaluation.[6]
References
  1. PASHOS CL, BOTTEMAN MF, LASKIN BL, REDAELLI A. Bladder cancer: epidemiology, diagnosis, and management. Cancer Pract [online] 2002 Nov-Dec, 10(6):311-22 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12406054
  2. MURARO GB, GRIFONI R, SPAZZAFUMO L. Endoscopic therapy of superficial bladder cancer in high-risk patients: Holmium laser versus transurethral resection. Surg Technol Int [online] 2005:222-6 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16525976
  3. BOLENZ C, CAO Y, ARANCIBIA MF, TROJAN L, ALKEN P, MICHEL MS. Intravesical mitomycin C for superficial transitional cell carcinoma. Expert Rev Anticancer Ther [online] 2006 Aug, 6(8):1273-82 [viewed 13 August 2014] Available from: doi:10.1586/14737140.6.8.1273
  4. STENZL ARNULF, COWAN NIGEL C., DE SANTIS MARIA, KUCZYK MARKUS A., MERSEBURGER AXEL S., RIBAL MARIA JOSé, SHERIF AMIR, WITJES J. ALFRED. Treatment of Muscle-invasive and Metastatic Bladder Cancer: Update of the EAU Guidelines. European Urology [online] 2011 June, 59(6):1009-1018 [viewed 13 August 2014] Available from: doi:10.1016/j.eururo.2011.03.023
  5. MEEKS JJ, BELLMUNT J, BOCHNER BH, CLARKE NW, DANESHMAND S, GALSKY MD, HAHN NM, LERNER SP, MASON M, POWLES T, STERNBERG CN, SONPAVDE G. A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol [online] 2012 Sep, 62(3):523-33 [viewed 13 August 2014] Available from: doi:10.1016/j.eururo.2012.05.048
  6. BAMIAS A.. Systemic chemotherapy in inoperable or metastatic bladder cancer. Annals of Oncology [online] 2006 April, 17(4):553-561 [viewed 14 August 2014] Available from: doi:10.1093/annonc/mdj079