16:30-18:30 WS #67: Urology Forum - Prostate Cancer, Stones, Renal Tumours, Voiding Dysfunction (120 minutes, not repeated) -

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1 Dr Anna Lawrence Urologist Auckland Dr Andrew Williams Urologist Auckland Madhu Koya Urologist Auckland Andrew Lienert Urologist Auckland Dr Louise Tomlinson Consultant Gynaecologist Auckland 16:30-18:30 WS #67: Urology Forum - Prostate Cancer, Stones, Renal Tumours, Voiding Dysfunction (120 minutes, not repeated) -

2 Bladder Cancer Madhusudan P Koya FRCS; FRACS Consultant Urologist Onesixone Medical Group, Auckland

3 Bladder cancer: Epidemiology Incidence: new cases per year [2016-USA] Mortality: deaths per year [2016-USA] Fourth most common cancer in men Seventh most common cancer in women At diagnosis >70%: > 65 y of age

4 Bladder Cancer in NZ 370 [270M] new registrations per year 170 [118M] deaths per year Maori:Non Maori 1:1 [from 1:2.5 in 1997] Steady death rate with no decline in the last 15 years Incidence has also remained steady

5 Bladder Cancer Bladder cancer is the fifth most common cancer in the Western world and is on the rise. Most patients present with superficial disease and are treated by transurethral resection of bladder tumour. More than half of these patients experience recurrence with about 20% progressing to muscle invasive disease. Muscle invasive cancer is treated by Radical Cystectomy or Chemoradiation

6 Risk Factors Smoking Exposure to Aniline dyes Schistosomiasis Radiation exposure Chronic irritation

7 Clinical Features Visible Haematuria Dysuria Abdominal pain Constipation UTI Raised Creatinine Raised inflammatory markers Raised WCC

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10 Visible haematuria With a high PPV of 2.6% this remains the main clinical feature in primary care that must lead to investigations and follow up

11 The Problem Is it cancer? Is it an emergency? Can I ignore it?

12 Emergencies Heavy Bleeding Causing Hypovolaemia Clot Urinary Retention Anaemia

13 Other Causes of Red Urine Myoglobin, Haemoglobin Porphyrins Phenolpthalien (laxatives) Rifampicin, Phenothiazines Betroot, Rhubarb.

14 Frank V Microscopic Malignancy could present as frank or microscopic haematuria

15 Classical description 1 Gross Total Painless Haematuria TCC Bladder

16 Normal? More than 3 RBC per High power field is abnormal

17 Classical description 2 Gross Haematuria with Flank Pain/Mass Renal Cell Cancer

18 Classical description 3 Loin - GroinPain Microscopic Blood Stone

19 Gross Haematuria Most Common site in order: 1. Bladder 2. Prostate 3. Kidney/Ureter 4. Other

20 Gross Haematuria Common Causes 1st 2nd 3rd Inflammation Neoplasia Foreign Body

21 Microscopic Haematuria 80% -No Important Cause Found 20% -Important Cause found

22 Haematuria 15-20% of cases with macroscopic haematuria had malignancy 10% of patients with microhaematuria had malignancy

23 Investigations? Microscopic Haematuria Microscopy to confirm Ultrasound Urine cytology Cystoscopy Further investigations [CTIVU] to be considered. Follow up?

24 Investigations? Always Investigate Gross Haematuria Ultrasound Urine Cytology Cystoscopy Consider CTIVU, RGP, Ureteroscopy Etc. If cause not found

25 Testing for Bladder cancer White light cystoscopy is the gold standard with a sensitivity of 90% But invasive and expensive Limits compliance Urine cytology is highly specific [99%] but limited by Low sensitivity [34%] especially in low grade Inter observer variations

26 Need for a good biomarker To improve management Improve quality of life of patients Decrease morbidity associated with current tests *A noninvasive, highly sensitive and specific marker required

27 Need for a good biomarker A good diagnostic marker should Have a low false positive rate A good surveillance marker should Have a high sensitivity and High negative predictive value

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29 mrna based urinary marker Cx bladder detect Sensitivity 82% NPV 98% Cost approx. $400 Cx bladder triage Sensitivity 95% NPV 98% Cx bladder

30 Bladder cancer: Histology 90-95% Urothelial carcinoma 3% squamous-cell carcinoma 2% adenocarcinoma <1% small-cell carcinoma

31 Bladder cancer: Histology 75-85% Nonmuscle invasive bladder cancer pta [70%], ptis [10%], pt1 [20%] 10-15% muscle-invasive bladder cancer pt2, pt3, pt4 5% metastatic bladder cancer N+, M+

32 Bladder cancer: Stage and Prognosis Stage TNM 5-y. Survival 0 Ta/Tis N0M0 >85% I T1 N0M % II T2a-b N0M0 57% III T3a-4a N0M0 31% IV T4b N0M0 24% Any T N+Mo 14% Any T M+ med. 6-9 Mo

33 Nonmuscle invasive Bladder Cancer pta, pt1, Tis Standard of care transurethral resection Relapse rate: 70% Progression rate 30% *Due to the recurrence rate highest lifetime treatment cost per person of all cancers

34 Nonmuscle invasive Bladder Cancer Histological grading is important G1 G2 G3 Relapse rate 42% 50% 80% Progression rate 2% 11% 45%

35 Invasive bladder cancer 5 year survival is 38% Standard of care = Radical cystectomy with pelvic lymphadenectomy Only about 50% of patients with high-grade invasive disease are cured

36 Results of radical cystectomy Stage Recurrence-Free Overall Survival 5 y. 10y. 5 y. 10y. T2 N N T3a N N T3b N N T4a N N Stein et al JCO 2001;19:666

37 Results of radical cystectomy Stage Recurrence-Free /Overall Survival 5 years Organ-confined (<pt2pno) 73% 62% non-organ-confined (>pt2pno) 56% 49% Positive lymph nodes (pt1-4, pn+) 33% 24% Madersbacher et al JCO 2003;21:690

38 Adjuvant chemotherapy Six randomised trials have compared CT with observation after cystectomy or RT 4x no survival benefit 2x benefit from adjuvant CT no standard of care node positive disease, lymphovascular invasion, positive margins

39 Neoadjuvant chemotherapy Meta-analysis of ten randomised trials (2688 patients) 13% reduction in risk of death 5% absolute benefit at 5 years OS increased from 45% to 50% ABC Meta-analysis Collaboration. Lancet 2003;361:1927

40 Combined Radio- and Chemotherapy CR 5y.OS Radiotherapy 57% 47% RT and cisplatin 85% 69% RT and carboplatin 70% 57% Birkenhake et al. Strahlenther Onkol 1998;174:121

41 Bladder-sparing therapy for invasive bladder cancer High probability of subsequent distant metastasis after cystectomy or radiotherapy alone (50% within 2 years) Radiotherapy im comparison with cystectomy has inferior results (local control 40%) muscle-invasive bladder cancer is often a systemic disease combined modality therapy

42 Bladder-sparing protocol Transurethral resection Induction Therapy: Radiation + chemotherapy (cisplatin based) Cystoscopy after 2 months no tumour tumour Consolidation: RT + CT cystectomy

43 Bladder-sparing protocol T2: 5y / 10y OS: 74% / 66% T3-T4a: 5y / 10y OS: 53% / 52% Shipley et al. Urology 2002;60:62

44 Results of bladder-sparing therapy and cystectomy Bladder-sparing n Pat. 5y. OS 5y. Survival therapy % with Bladder % Houssett NA Sauer Shipley Shipley Rodel

45 Disease-specific survival for patients after salvage cystectomy 50% 45% 21% 18% Rödel et al. JCO 2002;20:3061

46 TUR and adjuvant Radio-Chemotherapy 5 year Survival 50-65% Preservation of Bladder 38-43%

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64 Donald Lamm et al. Eur Urol Supp 1970;10:

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66 Thank you!

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