Background information Information resources for patients and carers Updates to this care map Bladder cancer - clinical presentation History Examination Consider differential diagnoses Clinical indications for urgent referral Refer urgently to urologist (within 2 weeks) Investigations Go to bladder cancer - diagnosis Haematuria with urinary tract infection (UTI) symptoms Unexplained nonvisible haematuria If no infection found, refer urgently to specialist urological cancer team Treat if infection confirmed Age 50 years or over - consider urgent referral to specialist urological cancer team Age under 50 years - test for proteinuria and serum creatinine Recurrent infection Consider urgent referral to specialist urological cancer team Refer urgently to specialist urological cancer team (within 2 weeks) Go to bladder cancer - diagnosis Proteinuria and raised serum creatinine Refer to renal physician Values normal Refer to urologist Refer urgently to specialist urological cancer team (within 2 weeks) Go to bladder cancer - diagnosis For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 1 of 10
1 Background information Scope: diagnosis and management of bladder cancer, both superficial and muscle-invasive urothelial carcinomas in primary and secondary care settings, for adults above age 18 years referral criteria for non-visible haematuria consideration of chemotherapy and radical radiotherapy treatment options discussion of bladder tumour resection as well as indications for cystoscopy treatment options for metastatic disease palliative care referral criteria Definition: over 90% of cancers of the urinary bladder are urothelial carcinoma (previously known as transitional cell carcinoma). Nonmuscle-invasive tumours are most common [1] non-muscle invasive tumours, ie no spread beyond the lamina propria, include: Ta non-invasive papillary carcinoma Tis carcinoma in situ ('flat tumour'): non-invasive, flat, full thickness, high grade dysplastic change in the urothelium high risk of progression to invasive disease T1 tumour invades subepithelial connective tissue (lamina propria) muscle invasive tumours, ie spread beyond the lamina propria, include: T2 tumour invades detrusor muscle T3 tumour invades perivesical tissue T4 tumour invades any of the following: prostate uterus vagina pelvic wall abdominal wall Incidence and prevalence: bladder carcinoma is the second most common malignancy of the urinary tract unusual in people below age 40 years [3] in males, incidence rises steeply with each decade between age 40-60 years [3]: 1.99 per 100,000 in those age 40-44 years [18] 10.96 per 100,000 in those age 50-54 years [18] 44.87 per 100,000 in those age 60-64 years [18] in females, incidence shows a similar rate of increase with age, with the proportion in each age group less than half the corresponding figures for males [3] Risk factors: cigarette smoke: significant dose-response relationship between the lifetime number of cigarettes smoked and risk of bladder cancer: triples the risk of developing bladder cancer smokers are 2-5 times more likely to develop bladder cancer than non-smokers [3] causes approximately 50-65% and 20-30% of cases in males and females respectively [4] occupational exposure to carcinogenic chemicals thought to account for up to 20% of cases [3]: highest risk occupations are those associated with high levels of exposure to: rubber dyes plastics related chemicals can cause bladder cancer 5-50 (typically 10-15) years later increasing age gender: estimated male to female ratio is 3.8:1 females more likely to be diagnosed with primary muscle invasive disease than males history of previous radiotherapy or chemotherapy (eg cyclophosphamide) long-term use of indwelling bladder catheters long-term use of chlorinated drinking water may increase the risk up to two-fold For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 2 of 10
chronic urinary tract infection (UTI): bladder schistosomiasis is considered a definitive cause of squamous cell carcinoma of the bladder dietary factors Prognosis: determined by depth to which tumour has invaded the bladder wall [5] 5-year survival in England, based on 1999-2003 data, is [18]: 61% for men 49% for women [1] Lamm D, Heeley M. Bladder cancer. BMJ Best Practice; 2010. [2] Contributors invited by Map of Medicine; 2010. [3] National Institute for Health and Clinical Excellence (NICE). Guidance on cancer services: improving outcomes in urological cancers the manual. London: NICE; 2002. [4] European Association of Urology (EAU). Guidelines on bladder cancer: muscle-invasive and metastatic. The Netherlands: EAU; 2010. [5] European Association of Urology (EAU). Guidelines on TaT1 (non-muscle invasive) bladder cancer. The Netherlands: EAU; 2009. [6] Scottish Intercollegiate Guidelines Network (SIGN). Management of transitional cell carcinoma of the bladder. SIGN publication no. 85. Edinburgh: SIGN; 2005. [18] Contributors representing the National Cancer Action Team; 2010. 2 Information resources for patients and carers Patients and carers in England can access this care map through NHS Choices at http://healthguides.mapofmedicine.com/choices/ map/bladder_cancer1.html The following resources have been produced by organisations certified by The Information Standard: 'Bladder cancer' (URL) from Bupa at http://www.bupa.co.uk 'Bladder cancer' (URL) from Cancer Help UK at http://www.cancerhelp.org.uk 'Bladder cancers' (URL) from Datapharm at http://www.medguides.medicines.org.uk 'Bladder cancer' (URL) from Macmillan Cancer Support at http://www.macmillan.org.uk 'Bladder cancer' (PDF) from Patient UK at http://www.patient.co.uk 'Bladder cancer - risk factors' (URL) from Cancer Research UK at http://www.cancerresearchuk.org 'Transurethral resection of bladder tumour (TURBT)' (URL) from Bupa at http://www.bupa.co.uk Information for carers and people with disabilities is available at: 'Caring for someone' (URL) from Directgov at http://www.direct.gov.uk 'Disabled people' (URL) from Directgov at http://www.direct.gov.uk Explanations of clinical laboratory tests used in diagnosis and treatment are available at 'Understanding Your Tests (URL) from Lab Tests Online-UK at http://www.labtestsonline.org.uk. The Map of Medicine is committed to providing high quality health and social care information for patients and carers. For details on how these resources are identified, please see Map of Medicine Patient and Carer Information. NB: This information appears on each page of this care map. 3 Updates to this care map Date of publication: 29-Apr-2011 Interim update: Definition of proteinuria added in line with the following reference: [20] National Institute for Health and Clinical Evidence (NICE). Early identification and management of chronic kidney disease in adults in primary and secondary care. Clinical guideline 73. London: NICE; 2008. Interim update: 31-Jan-2011 The clinical content of this care map has been accredited by the National Cancer Action Team Date of publication: 29-Oct-2010 Interim update: For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 3 of 10
This care map has been updated according to feedback from the National Cancer Action Team (NCAT): [18] Contributors representing the National Cancer Action Team; 2010. Date of publication: 30-Jul-2010 Three floating information points now appear at the top of each care map page. These provide: easy access to scope and background information on each page of the care map whilst reducing repetition between care points easy access to patient resources/leaflets information on care map updates This care map was updated in line with the following guidelines: [3] National Institute for Health and Clinical Excellence (NICE). Guidance on cancer services: improving outcomes in urological cancers the manual. London: NICE; 2002. [4] European Association of Urology (EAU). Guidelines on bladder cancer: muscle-invasive and metastatic. The Netherlands: EAU; 2010. [5] European Association of Urology (EAU). Guidelines on TaT1 (non-muscle invasive) bladder cancer. The Netherlands: EAU; 2009. [6] Scottish Intercollegiate Guidelines Network (SIGN). Management of transitional cell carcinoma of the bladder. SIGN publication no. 85. Edinburgh: SIGN; 2005. children. Clinical guideline 27. London: NICE; 2005. [9] Clinical Knowledge Summaries (CKS). Urological cancer suspected. Version 1.0. Newcastle upon Tyne: CKS; 2005. [11] Hall MC, Chang SS, Dalbagni G et al. Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol 2007; 178: 2314-30. [13] National Institute for Health and Clinical Excellence (NICE). Intravesical microwave hyperthermia with intravesical chemotherapy for superficial bladder cancer. Interventional procedure guidance 235. London: NICE; 2007. c [14] National Institute for Health and Clinical Excellence (NICE). Electrically-stimulated intravesical chemotherapy for superficial bladder cancer. Interventional procedure guidance 277. London: NICE; 2008. [17] Cancer Care Ontario. Use of neoadjuvant chemotherapy in transitional cell carcinoma of the bladder. Toronto, ON: Cancer Care Ontario; 2005. Further information was provided by the following references: [1,2,8,10,12,15,16]. For more information, please see the care map's Provenance certificate. Practice-based knowledge has been contributed to this care map by: Dr Anne E Kiltie: Clinical Group Leader/Honorary Consultant Clinical Oncologist, Gray Institute for Radiation Oncology and Biology, Oxford, UK Prof Howard Kynaston: Consultant in urology, Cardiff University Department of Surgery, Cardiff, Wales Selected members of the Clinical Editorial team and Fellows The care map has been completely restructured and redrafted in line with the Map of Medicine editorial methodology and to bring it in line with current clinical practice. NB: This information appears on each page of this care map. 4 Bladder cancer - clinical presentation Features include: visible haematuria (blood in the urine): present in 80-90% of patients [3,5] may be intermittent, but a single episode of haematuria can signal the presence of cancer non-visible haematuria: better predictor of cancer in older men more likely to be pathological in young men is less likely to be associated with any pathology in primary care, painful, urgent, or frequent urination (dysuria): usually suggests a urinary tract infection (UTI) and is rarely due to bladder cancer painful urination may indicate a bladder outlet obstruction 20-30% of patients eventually diagnosed with bladder cancer have these symptoms at presentation [4] Always consider the diagnosis, especially if symptoms are: associated with atypical features persistent refractory to UTI treatment Advanced disease may involve: For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 4 of 10
abdominal or pelvic mass (unusual at presentation) bone pain pelvic pain oedema of the lower limbs due to compression of the iliac vessels pain in the flank due to obstruction of the ureter weight loss cachexia [3] National Institute for Health and Clinical Excellence (NICE). Guidance on cancer services: improving outcomes in urological cancers the manual. London: NICE; 2002. [4] European Association of Urology (EAU). Guidelines on bladder cancer: muscle-invasive and metastatic. The Netherlands: EAU; 2010. [5] European Association of Urology (EAU). Guidelines on TaT1 (non-muscle invasive) bladder cancer. The Netherlands: EAU; 2009. 5 History Ask patient about: blood visible in urine dysuria, urgency, or frequency systemic symptoms of urinary tract infection (UTI) palpable abdominal or pelvic mass bone, pelvic, or flank pain lymphadenopathy history of: smoking work in the rubber, painting, or metal industries radiotherapy or chemotherapy, eg cyclophosphamide This information was drawn from the following reference: 6 Examination Examination is rarely revealing of bladder tumours an examination should include: pelvic examination to assess prostate or pelvic mass assessment for lymphadenopathy urinalysis This information was drawn from the following references: [4] European Association of Urology (EAU). Guidelines on bladder cancer: muscle-invasive and metastatic. The Netherlands: EAU; 2010. [5] European Association of Urology (EAU). Guidelines on TaT1 (non-muscle invasive) bladder cancer. The Netherlands: EAU; 2009. 7 Consider differential diagnoses Possible differential diagnoses for bladder cancer include: kidney cancer see 'Kidney cancer' care map urinary tract infection (UTI) non-infectious haemorrhagic cystitis For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 5 of 10
kidney stones see 'Kidney stones' care map prostate cancer see 'Prostate cancer' care map benign prostatic hyperplasia see 'Male lower urinary tract symptoms' care map This information was drawn from the following references: [4] European Association of Urology (EAU). Guidelines on bladder cancer: muscle-invasive and metastatic. The Netherlands: EAU; 2010. [8] Map of Medicine (MoM) Clinical Editorial team and Fellows. London: MoM; 2010. 8 Clinical indications for urgent referral Refer any patient presenting with any one of the following to the local specialist team for urological cancers patients should be seen within 2 weeks [4]: painless visible haematuria in the absence of symptoms suggesting a urinary tract infection (UTI) persistent UTI and haematuria (either visible or non-visible) particularly in those over age 40 years an abdominal mass with location consistent with a urinary tract origin palpable renal mass solid renal masses on imaging [4] National Institute for Health and Clinical Excellence (NICE). Referral guidelines for suspected cancer in adults and 10 Investigations Investigations should include the following [3]: urinalysis check particularly for: haematuria proteinuria leucocytosis urine culture if infection is suspected urine microscopy if haematuria is present but no signs of UTI, consider: red cell morphology on urinary sediment (morning sample) urine cytology (note high rate of false positives) [4,5] serum creatinine and urea [7,9] full blood count (FBC) [3] National Institute for Health and Clinical Excellence (NICE). Guidance on cancer services: improving outcomes in urological cancers the manual. London: NICE; 2002. [4] European Association of Urology (EAU). Guidelines on bladder cancer: muscle-invasive and metastatic. The Netherlands: EAU; 2010. [5] European Association of Urology (EAU). Guidelines on TaT1 (non-muscle invasive) bladder cancer. The Netherlands: EAU; 2009. [9] Clinical Knowledge Summaries (CKS). Urological cancer suspected. Version 1.0. Newcastle upon Tyne: CKS; 2005. 11 Haematuria with urinary tract infection (UTI) symptoms Patient has blood in urine and symptoms suggesting a urinary tract infection (UTI). 12 Unexplained non-visible haematuria For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 6 of 10
Non-visible haematuria is usually identified microscopically or chemically by dipstick there should be no frank blood in the urine [8]. Reference: [8] Map of Medicine (MoM) Clinical Editorial team and Fellows. London: MoM; 2010. 13 Age 50 years or over - consider urgent referral to specialist urological cancer team Consider referral to the local specialist urological cancer team patients should be seen within 2 weeks [6,7,9]: for patients age 50 years and above; with unexplained non-visible haematuria [6] Scottish Intercollegiate Guidelines Network (SIGN). Management of transitional cell carcinoma of the bladder. SIGN publication no. 85. Edinburgh: SIGN; 2005. [9] Clinical Knowledge Summaries (CKS). Urological cancer suspected. Version 1.0. Newcastle upon Tyne: CKS; 2005. 14 Age under 50 years - test for proteinuria and serum creatinine Test patients age 50 years and below with unexplained non-visible haematuria for [7,9]: proteinuria serum creatinine level [9] Clinical Knowledge Summaries (CKS). Urological cancer suspected. Version 1.0. Newcastle upon Tyne: CKS; 2005. 15 If no infection found, refer urgently to specialist urological cancer team Patients with unexplained visible haematuria should be referred to a urologist within the local multidisciplinary team (MDT) for urological cancers and seen within 2 weeks [7]. Reference: 16 Treat if infection confirmed Treat the urinary tract infection (UTI) [7]: if the infection and features (including haematuria) do not resolve or if it recurs, consider referral to specialist urological cancer team Reference: 17 Recurrent infection For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 7 of 10
Recurrent urinary tract infection (UTI) is infection that is initially treated but returns at least once [8]. Reference: [8] Map of Medicine (MoM) Clinical Editorial team and Fellows. London: MoM; 2010. 19 Proteinuria and raised serum creatinine Consider referral to a renal physician [6,7,9]: for patients below age 50 years; with unexplained non-visible haematuria; and proteinuria and raised serum creatinine Significant proteinuria [18]: in people without diabetes, consider clinically significant proteinuria to be present when the albumin/creatinine ratio (ACR) is 30mg/mmol or more (this is approximately equivalent protein:creatinine ratio 50mg/mmol, or a urinary protein excretion 0.5g/24hours or more) in people with diabetes, consider microalbuminuria (ACR more than 2.5mg/mmol in men and ACR more than 3.5mg/mmol in women) to be clinically significant [6] Scottish Intercollegiate Guidelines Network (SIGN). Management of transitional cell carcinoma of the bladder. SIGN publication no. 85. Edinburgh: SIGN; 2005. [9] Clinical Knowledge Summaries (CKS). Urological cancer suspected. Version 1.0. Newcastle upon Tyne: CKS; 2005. [20] National Institute for Health and Clinical Evidence (NICE). Early identification and management of chronic kidney disease in adults in primary and secondary care. Clinical guideline 73. London: NICE; 2008. 20 Values normal Consider non-urgent referral to a urologist [6,7,9]: for patients below age 50 years; with unexplained non-visible haematuria; but no proteinuria and normal serum creatinine [6] Scottish Intercollegiate Guidelines Network (SIGN). Management of transitional cell carcinoma of the bladder. SIGN publication no. 85. Edinburgh: SIGN; 2005. [9] Clinical Knowledge Summaries (CKS). Urological cancer suspected. Version 1.0. Newcastle upon Tyne: CKS; 2005. 21 Consider urgent referral to specialist urological cancer team If a urinary tract infection (UTI) associated with visible haematuria does not resolve on treatment, or recurs, refer patient urgently (to be seen within 2 weeks) to a urologist within the local multidisciplinary team (MDT) for urological cancers [7]: this is to exclude malignancy as a first priority, although there are a variety of benign causes for persistent or recurrent UTI Reference: For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 8 of 10
Key Dates, by International Valid until: 29-Feb-2012 Accreditations The care map is accredited by: National Cancer Action Team (NCAT): Disclaimer The care map is accredited by: The Chief Knowledge Officer of the NHS: Disclaimer Evidence summary for This pathway has been developed according to the Map of Medicine editorial methodology (http://mapofmedicine.com/ whatisthemap/editorialmethodology). The content of this pathway is based on high-quality guidelines [1,3-7,9,11,13,14,17,20], critically appraised meta-analyses and systematic reviews [12,15,16] and safety and prescribing information [10]. Practice-based knowledge has been added by contributors with front-line clinical experience [2,8,18], including any literature endorsed by the contributor group [19]. The evidence-based, practice-informed pathway has been peer-reviewed by central committees within stakeholder groups. Search date: Mar-2010 References This is a list of all the references that have passed critical appraisal for use in the care map Bladder cancer ID Reference 1 Lamm D, Heeley M. Bladder cancer. BMJ Best Practice; 2010. 2 Contributors invited by Map of Medicine. 2010. 3 National Institute of Health and Clinical Excellence (NICE). Guidance on cancer services: improving outcomes in urological cancers - the manual. London: NICE; 2002. http://www.nice.org.uk/nicemedia/pdf/urological_manual.pdf 4 European Association Urology (EAU). Guidelines on bladder cancer: muscle-invasive and metastatic. The Netherlands: EAU; 2010. http://www.uroweb.org/gls/pdf/muscle%20inv%20&%20metastatic%20bc%202010.pdf 5 European Association Urology (EAU). Guidelines on TaT1 (non-muscle invasive) bladder cancer. The Netherlands: EAU; 2009. http://www.uroweb.org/gls/pdf/tat1%20(non-muscle%20invasive)%20bladder%20cancer%202010.pdf 6 Scottish Intercollegiate Guidelines Network (SIGN). Management of transitional cell carcinoma of the bladder. Clinical Guideline 85. Edinburgh: SIGN; 2006. http://www.sign.ac.uk/pdf/sign85.pdf 7 National Institute for Health and Clinical Excellence (NICE). Referral guidelines for suspected cancer. Clinical guideline 27. London: NICE; 2005. http://www.nice.org.uk/nicemedia/pdf/cg027niceguideline.pdf 8 Map of Medicine (MoM) Clinical Editorial team and Fellows. London: MoM; 2010. 9 Clinical Knowledge Summaries (CKS). Urological cancer - suspected. Version 1.0. Newcastle upon Tyne: CKS; 2005. http://www.cks.nhs.uk/urological_cancer_suspected#394927001 10 Department of Health (DH). Going further on cancer waits. London: DH; 2008. http://www.library.nhs.uk/improvement/viewresource.aspx?resid=322870 11 Hall MC, Chang SS, Dalbagni G et al. Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol 2007; 178: 2314-2330. 12 Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a metaanalysis of published results of randomized clinical trials. J Urol 2004; 171: 2186-90, quiz. For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 9 of 10
ID Reference 13 National Institute for Health and Clinical Excellence (NICE). Intravesical microwave hyperthermia with intravesical chemotherapy for superficial bladder cancer. Interventional procedure guidance 235. London: NICE; 2007. http://www.nice.org.uk/nicemedia/live/11364/38015/38015.pdf 14 National Institute for Health and Clinical Excellence (NICE). Electrically-stimulated intravesical chemotherapy for superficial bladder cancer. Interventional procedure 277. London: NICE; 2008. http://www.nice.org.uk/nicemedia/live/11941/42571/42571.pdf 15 Han RF, Pan JG. Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with superficial bladder cancer? A meta-analysis of randomized trials. Urology 2006; 67: 1216-1223. 16 Babjuk M, Oosterlinck W, Sylvester R. Guidelines on TaT1 (non-muscle invasive) bladder cancer. The Netherlands: European Association of Urology (EAU); 2009. 17 Cancer Care Ontario. Use of neoadjuvant chemotherapy in transitional cell carcinoma of the bladder. Toronto, ON: Cancer Care Ontario; 2005. 18 Contributors representing the National Cancer Action Team. 2010. 19 Donat SM, Herr HW, Bajorin DF et al. Methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy and cystectomy for unresectable bladder cancer. J Urol 1996; 156: 368-371. http://www.ncbi.nlm.nih.gov/pubmed/8683681 20 National Institute for Health and Clinical Excellence (NICE). Early identification and management of chronic kidney disease in adults in primary and secondary care. Clinical guideline 73. London: NICE; 2008. http://www.nice.org.uk/cg73 Disclaimers National Cancer Action Team (NCAT) It is not the function of the National Cancer Action Team to substitute for the role of the clinician, but to support the clinician in enabling access to know-how and knowledge. Users of the Map of Medicine are therefore urged to use their own professional judgement to ensure that the patient receives the best possible care. Whilst reasonable efforts have been made to ensure the accuracy of the information on this online clinical knowledge resource, we cannot guarantee its correctness or completeness. The information on the Map of Medicine is subject to change and we cannot guarantee that it is up-to-date. The Chief Knowledge Officer of the NHS It is not the function of the Chief Knowledge Officer of the NHS to substitute for the role of the clinician, but to support the clinician in enabling access to know-how and knowledge. Users of the Map of Medicine are therefore urged to use their own professional judgement to ensure that the patient receives the best possible care. Whilst reasonable efforts have been made to ensure the accuracy of the information on this online clinical knowledge resource, we cannot guarantee its correctness or completeness. The information on the Map of Medicine is subject to change and we cannot guarantee that it is up-to-date. For terms of use please see our Terms and Conditions http://mapofmedicine.com/map/legal Page 10 of 10