Haematuria and Modern Bladder Cancer Treatment Mr Nikhil Vasdev MBBS MRCS MCh(Urol) FRCS(Urol) RCSEng/BAUS Robotic Fellowship Accredited and Trained Consultant Urological and Robotic Surgeon Hertfordshire and Bedfordshire Urological Cancer Centre Department of Urology Lister Hospital UK Associate Lecturer in Urology University of Cambridge Senior Clinical Lecturer in Urology University of Hertfordshire www.nvasdevurology.com
Case 1 72 Year / Male Worked in construction for 40 years Past H/O Hypertension, Hypercholesterolaemia Smoker with 50 year pack history Family H/O Prostate cancer (Brother aged 60) Symptoms Blood in pee 2 weeks
History Taking Personal o Gender (Female, Male) o Age (Older, Younger) Main Complaint Haematuria +/- Associated Symptom Duration o Acute / Chronic History of presenting complaint o Onset- Sudden, Progressive, Transient, Persistent, Recurrent o Patter Gross versus microscopic, extra gromerular o Painful versus Painless
History Taking Past History o Urological Malignancy o Renal Stones o Urinary tract infections o Previous Abdominal Surgery, Pelvic Radiotherapy History of smoking Occupational History Drug History : Anticoagulation
Common Symptom in clinic I have had some discomfort whilst voiding but my symptoms have been on-going for 2 weeks
Initial Investigations Urine dipstick: Significant haematuria is 1+ or greater Trace haematuria is not significant and should be considered negative Proteinuria Transient causes must be excluded before the presence of significant haematuria can be established: Urinary tract infection (UTI): A diagnosis of UTI may be excluded if urine dipstick is negative for both leucocytes and nitrites ii urine dipstick is positive for either leucocytes or nitrites the sample must be sent for microscopy and culture negative pyuria and culture excludes UTI
Important Considerations Consider a prostate-specific antigen (PSA) test and a digital rectal examination to assess for prostate cancer in men with visible haematuria Consider direct access ultrasound scan to assess for endometrial cancer if vaginal bleeding cannot be excluded
Common Causes of Haematuria
What is the definition of Haematuria Joint Consensus Statement (Renal Association / British Association of Urological Surgeons) Visible Haematuria (VH). Otherwise referred to as macroscopic haematuria or gross haematuria Non-Visible Haematuria (NVH). Otherwise referred to as microscopic haematuria or dipstick positive haematuria. This is further sub-divided as follows: o Symptomatic Non-Visible Haematuria (s-nvh). Symptoms such as voiding lower urinary tract symptoms (LUTS): hesitancy, frequency, urgency, dysuria o Asymptomatic Non-Visible Haematuria (a-nvh). Incidental detection in the absence of LUTS or upper urinary tract symptoms
What is Significant Haematuria? Any single episode of VH Any single episode of s-nvh (in absence of UTI or other transient causes) Persistent a-nvh (in absence of UTI or other transient causes). Persistence is defined as 2 out of 3 dipsticks positive for NVH
What is Significant Haematuria? Transient causes that need to be excluded before establishing the presence of significant haematuria are:- o Urinary tract infection (UTI) o Haematuria in association with UTI is not uncommon o UTI is most readily excluded by a negative dipstick result for both leucocytes and nitrites o Otherwise an MSU negative for pyuria and culture are required o Exercise induced haematuria or rarely myoglobinuria (VH and NVH) o Menstruation
2 WW For Bladder Cancer Age 45 and over Visible Haematuria (in the absence of UTI) and / or Visible haematuria that persists or recurs after successful treatment of urinary tract infection Age 60 and over NVH and either dysuria / raised WBC on blood test Non-urgent Referral Age 60 and over Recurrent / Persistent unexplained UTI
In 2008 British Association of Urological Surgeons (BAUS) haematuria guidelines recommend referral to urology for all patients with visible haematuria, regardless of age
2 WW For Renal Cancer Unexplained visible haematuria without urinary tract infection or Visible haematuria that persists or recurs after successful treatment of urinary tract infection
Nephrological Referral The need for a nephrology referral in this situation depends on factors other than simply the presence of haematuria NICE guidelines recommend a recommended if there is concurrent: o Evidence of declining GFR (by >10ml/min at any stage within the previous 5 years or by >5ml/min within the last 1 year) o Stage 4 or 5 CKD (egfr <30ml/min) o Significant proteinuria (ACR 30mg/mmol or PCR 50mg/ mmol) Isolated haematuria (i.e. in the absence of significant proteinuria) with hypertension in those aged <40 o Visible haematuria coinciding with intercurrent (usually upper respiratory tract) infection
Focused History
Analysis of 1740 patients attending a haematuria clinic 1067 men and 673 women 161 had a positive MSU o 20% had malignancy pick up 1249 with no UTI history and negative MSU o 24% had malignancy pick up
Despite selection bias inherent in this analysis, it appears that the presence of UTI does not decrease the likelihood of having a urologic malignancy diagnosed Hence, there is no indication to delay prompt evaluation in patients with haematuria and a positive urine culture collected at the haematuria clinic
What is the incidence of diagnosing a urological malignancy when a patient has haematuria? Symptom Diagnosis of Bladder Cancer Gross Visible Haematuria 20 % Non Visible Haematuria 2 %
What is the incidence of diagnosing a urological malignancy when a patient has haematuria? Symptom Diagnosis of Bladder Cancer Gross Visible Haematuria 20 % Non Visible Haematuria 2 % Irritative voiding symptoms 20% of patients (Concerning symptom of Carcinoma in Situ )
Conclusion Patients with haematuria are investigated promptly. The 2 week rule has increased the cancer detection rate
Is it time for a Haematuria screening programme in the UK? 1992 Britton et al dipstick test in 2356 patient Bladder cancer diagnosis 5.3 % of cohort Conclusion Large number of asymptomatic men screened and increased screening cost with no benefit
Current statistics on Cancer in England Early diagnosis of cancer is a major priority for the Government in helping to improve cancer survival It has been estimated that 10,000 deaths could be avoided each year if cancer survival in England matched the best in Europe Research evidence indicates low public awareness of the signs and symptoms of cancer
Cancer Research UK Public Health England National Patient Awareness and Early Diagnosis initiative NHS England Blood in Pee Campaign Department of Health Target populous is patients above 50 years
Important points to the public If you notice blood in your pee, even if it s just the once, tell your doctor Look before you flush This campaign aims to encourage increase symptom awareness of bladder / kidney cancer and to increase early diagnosis of both conditions
Aim To evaluate the potential impact of increased patient awareness with the Blood in the pee campaign on Urological referrals To evaluate stage / grade changes in bladder and kidney cancer with Blood in the pee campaign
GP A\endances There was a 32% increase in the number of GP attendances, compared with the same period in the previous year This is equivalent to an additional 0.29 visits per practice, per week.
Diagnostic investigations Ultrasound scans There was considerable variability in the recorded number of diagnostic ultrasounds (ultrasound of kidney, ultrasound & Doppler scan of kidney and ultrasound of bladder), in total and from both GP and consultant referrals There were no clear changes relating to the first national campaign but the variability makes it difficult to draw firm conclusions about this
Diagnostic investigations Cystoscopies There was a 3% increase in the total cystoscopy activity for December 2013 to May 2014, compared to Dec 2012 to May 2013. For waiting list cystoscopy activity, there was an 8% increase over the same period
Urgent GP referrals for suspected cancer Following both first and second national campaigns, there were increases in the number of urgent GP referrals for suspected urological cancers For comparator referrals, there were increases of 13% and 24%
Diagnoses resulting from 2WW referrals The number of diagnoses resulting from a 2WW referral increased for o Bladder (8.2%), o Kidney (22%) o Urological (14%) cancers
Current patient data from the Blood in pee campaign Blood in pee is a key symptom in 53% of bladder cancer patients and 18% of kidney cancer patients In 2013 o 3,340 bladder and kidney cancers were diagnosed through an emergency presentation in England (majority metastatic at presentation) o Around a fifth of all cases for bladder and kidney cancers
Modelling of possible impact on services Following the second national campaign, the number of referrals per working day peaked in December 2014 On average, each trust saw approximately 6 extra referrals per week, during November and December 2014
Data summary The Blood in pee campaign has increased public awareness of this important symptom Patient awareness has led to increase Cancer specific referrals both to GP s and Hospitals
East and North Herts Haematuria Clinic Urine Dipstick /? Cytology egfr Ultrasound urinary tract / CT Urogram Formal Clinical History and Full examination including a DRE Flexible Cystoscopy
Urine Cytology Mid Morning Urine sample Sensitivity o 84% in High grade bladder cancer o 16 % in Low grade bladder cancer Overall o 10-90% Sensitivity o 30 50 % Specificity
Newer Biomarkers Sensitivity Specificity UroVysion (FISH) 30-86 % 63-95% Microsatelite analysis 58-92% 73-100% ImmunoCyt/uCyt + 52-100% 63-79% NMP22 (Bladder Chek) 47-100% 55-98% BTA stat 53-91% 56-86% BTA TRAK 53-91% 28-83% Cytokeratins 12-88% 73-95% Telomerase (TRAP) 74% 79 None of these markers have been accepted for diagnosis or follow up in patients with Bladder Cancer Vasdev N et al. Haematuria. Nova Book New York 2015 EAU Guidelines 2016
Diagnosis Test Ultrasound
CT Urogram Diagnosis Test
Important Considerations before requesting CT Scans for Haematuria Iodinated Contrast Media Allergy o More common if history of allergy o 2-4% = mild allergic reaction (Uticaria) o <1% = severe reaction (Broncospasm, Circulatory collapse) o Death rate estimated at 1:40-100,000 Nephrotoxic o High risk Creatinine > 200 umol/: Diabetes Heart Failure Myeloma NSAID s Gadolinium Contrast o GFR < 30 = High risk of Nephrogenic Systemic Fibrosis
Diagnosis Test Flexible Cystoscopy (Diagnostic Examination of Bladder)
Causes of Blood in urine Bladder Cancer
East and North Herts Blue Light Cystoscopy Programme Commences December 2016
Blue Light Cystoscopy
Advantages of Blue light cystoscopy Blue light cystoscopy has a higher sensitivity than white light cystoscopy o Patient level (92 % Versus 71 %) o Biopsy level (93 % Versus 65 %) o A metaanalysis reported a reduction in tumour recurring <10% within 12 months
Current Radical Cystectomy techniques offered at East and North Herts NHS Trust Open Cystectomy Robotic Cystectomy Open Neobladders Robotic Ileal Conduit
Robotic versus Open radical cystectomy for bladder cancer- A Systematic Review of Randomised Control Trails Bhavan Rai, Jim Adshead, Nikhil Vasdev et al submi\ed to Cochrane Reviews in Urology on 8 th September 2016 Advantages of Robotic Cystectomy over open Decreased fluid loss due to evaporation Decreased blood loss Decreased pain Shorter recovery Less bowel manipulation than with extracorporeal technique Quicker return of bowel function with less hospital stay Need to use less distal ureter (potential for lower rate of strictures) Smaller incision
Conclusion The NICE guideline development group recognized that the recommendations would be unlikely to cover all patients with bladder or renal cancer; however as with all NICE clinical guidelines, the recommendations are for guidance only and do not replace clinical judgment Primary care practitioners will still be expected to refer a patient who does not meet the guideline criteria for suspected bladder or renal cancer if they are concerned and think it necessary
Contact nikhil.vasdev@nhs.net www.nvasdevurology.com Private Practice location / Details privatesecvasdev@icloud.com 07767 486647 (Location Pinehill Hospital Hitchin Spire Bushey Hospital, North London)