Bladder cancer diagnosis and management

Bladder cancer is the second most common urological malignancy with approximately 10,500 new cases diagnosed every year in the UK.¹ The commonest presentation for bladder cancer is haematuria with painless visible haematuria being the primary presentation in 85% of bladder cancers. NICE guidance for urgent referral via the two-week wait pathway to urologists includes:²

• Patients of any age with painless visible haematuria
• over 40 years with recurrent/persistent urinary tract infections and haematuria
• over 50 years with unexplained microscopic haematuria.

The Joint Consensus Statement for Initial Investigation of Haematuria on behalf of the Renal Association and the British Association of Urological Surgeons (July 2008) suggests the following as referral criteria to urologists:³All patients with visible haematuriaAll patients with symptomatic non-visible haematuria (s-NVH)All patients with asymptomatic non-visible haematuria (a-NVH) aged over 40 years age.

Trace haematuria on urine dipstick should be considered negative while over one or more is considered significant.Symptomatic non-visible haematuria is associated with symptoms such as voiding lower urinary tract symptoms in the absence of UTI or transient causes eg. exercise-induced haematuria, myoglobinuria and menstruation.

Urine dipstick of a fresh voided urine sample with no preservative is considered sensitive and routine microscopy for confirmation is not necessary. For haematuria in association with UTI, a dipstick should be repeated post-treatment to confirm resolution of haematuria. If haematuria persists, then further investigations should be carried out if clinically indicated as UTI can be the first presentation of significant genitourinary pathology.

Haematuria clinicsThe role of one-stop haematuria clinics is early recognition and thus early intervention for urological cancers. Early diagnosis has shown the one-year survival for bladder and renal cancers to be as high as 92€“97%, but if diagnosed late it significantly falls down to only 25€“34%.⁴ Currently only 30% of bladder cancers and 19% of kidney cancers are being diagnosed via the two-week wait referral pathway.⁵ The €œBe Clear on Cancer€ campaign is part of the Government’s Improving Outcomes: A strategy for cancer. The aim is to prevent 5,000 cancer deaths per year by 2014/15, which would bring survival in England up to the average for Europe. The €œBlood in Pee€ campaign aims to get people with appropriate symptoms to present earlier to their GPs and where appropriate, be referred on promptly for investigation.⁶The importance of these clinics was shown by two large studies. Khadra et al showed a 12% incidence of bladder cancer with haematuria with 5.2% incidence in patients with microscopic haematuria.⁷ Edwards et al showed a 10% incidence of bladder cancer with 1.5% incidence of renal cell cancer (RCC) and only 0.5% upper tract urothelial cancer in approximately 4,000 patients assessed in such clinics.8 More significantly, it was noted that the incidence of malignancy was nearly 20% with visible haematuria as compared to 5% with microscopic haematuria.The recommended investigations in the one-stop haematuria clinic are:^9,10€¢ History and general examination€¢ Bloods (FBC, U&Es, clotting)€¢ Urine for microscopy, culture, sensitivity€¢ Urine for cytology€¢ Upper tract imaging€¢ Flexible cystoscopy

History and examinationPhysicians should look to see if the haematuria is visible versus non-visible, symptomatic versus asymptomatic and for the presence or absence of clots. Other factors include colour and timing in stream and constitutional, systemic and bony symptoms. Risk factors include smoking (amount, duration), occupational exposure, family history. Examination should be of the abdominal to look for any masses as well as a digital rectal examination.

Cytology versus novel urinary markersUrine cytology is most useful in the detection of high-grade tumours with 98.3% specificity and 38% sensitivity.¹¹ Several novel markers have been developed to aid detection of low-grade disease. NMP-22 (nuclear matrix protein 22) was marketed as Alere NMP-22 Bladder Chek® with 88% sensitivity and 67% specificity in newly diagnosed bladder cancer patients.¹² However it lacked the same efficacy for CIS (carcinoma-in-situ). UroVysion® seems to be a promising test with 81% sensitivity and 96% specificity.¹³ However, it is a complicated test, which requires intact cells, expensive equipment and a dedicated laboratory (ie. it is not a bedside test and its use in the one-stop clinics is not practical). None of the urinary markers including cytology have proven effective enough to replace cystoscopy but are useful as adjuncts to improve diagnostic efficacy and follow-up.

Role of flexible cystoscopyFlexible cystoscopy remains the gold-standard test in diagnosis of bladder cancer. White light cystoscopy (WLC) remains the current standard for diagnosis and follow-up of bladder cancer. However, the sensitivity ranges from 62€“84% and specificity varies from 43€“98%.¹⁴ Narrow-band imaging (NBI) is a proposed alternative in an effort to improve the accuracy of cystoscopy. It relies on filtering white light into two narrow bandwidths of light centred on blue (415nm) and green (540nm) colours, which penetrate tissue only superficially and are specifically absorbed by haemoglobin.^15,16 Bladder cancers tend to be very vascular and hence NBI increases the contrast between these tumours and normal bladder mucosa. The focus on improving the accuracy of initial cystoscopy is to allow accurate identification and resection thereby reducing residual tumour and recurrence rates.¹⁷

Why scan upper urinary tracts? 

The incidence of upper urinary tract epithelial tumours is 1.5 in 100,000 patients and that of renal cell cancers is 10 in 100,000. The chance of missing a tumour at four years median follow-up with ultrasound, x-ray Kidneys-Ureters-Bladder and urine cytology is 1.7%.¹⁸ Also, the incidence of upper urinary tract epithelial cancer is 2€“3% after diagnosis of bladder cancer.¹⁹  

Ultrasound is a useful initial imaging modality as it is cheap, easily available and carries no radiation risk. However, it remains operator-dependent and therefore does not carry the same sensitivity and specificity of CT imaging. CT urogram has been shown to have a significantly higher sensitivity than conventional excretory urography in detecting upper tract pathology (94% versus 50%).²⁰ There have been suggestions to use CT urogram as triage to proceed directly to rigid cystoscopy under anaesthetic as possibly 17% fewer flexible cystoscopies might have been performed.²¹ However, CT urogram should be used judiciously as there are economic implications from unsuspected findings such as diverticular disease, adrenal masses, gallstones and aortic aneurysms.²²

To screen or not to screen for bladder cancer?The current consensus is that bladder screening is not cost-effective. Britton et al noted an incidence of 20% dipstick haematuria in >2,300 men over the age of 60 years. However, only 0.72% overall incidence of bladder cancer was noted in these men.23 Steiner et al tried targeted screening of smokers using cytology and novel markers. The detection rate was 3.3% with the most effective combination being urine dipstick, cytology and UroVysion.²⁴

Role of urology clinical nurse specialistsClinical nurse specialists (CNSs) have been widely acknowledged as key to improving patient experience for people with cancer. Cancer strategies in England²⁵ and Scotland²⁶ have recognised the important role played by CNSs in supporting patients with cancer and improving patient care. CNSs bring a patient-centred approach to cancer care by providing support, advice and information to patients and their families. They also are able to take pressure off doctors by being able to spend time with them when they need it.²⁷ Therefore it is important to have a CNS attached to the one-stop haematuria clinic so that they can establish an early rapport with the patients and help them throughout their journey.The one-stop haematuria clinics also form a pivotal point in implementing preventative strategies for patients diagnosed with cancer. Bladder cancer is the second most common tobacco-related malignancy. 

Therefore these clinics give an opportunity to imprint the importance of smoking cessation on patients. A Californian study showed that 74% patients with bladder cancer diagnosis were smokers with 17% being active smokers at the time of diagnosis. However, smokers newly diagnosed with bladder cancer were five times more likely to quit smoking than smokers in the general population.²⁸

These consultations can also be used to imprint the importance of other lifestyle measures such as weight loss and healthy diet as cancer survivors are at an increased risk of other health issues such as osteoporosis, obesity, diabetes and cardiovascular disease. There is often only selective uptake of this advice and only 20% of oncologists were shown to be offering such guidance.²⁹

Part two and three of this article will be published in the next editions of GM Journal.

Conflict of interest: none declared

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