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Dr Manish Patel MB.BS., MMed., FRACS Urological Oncologist

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1 A Guide to the Diagnosis, Treatment and Follow-Up of Bladder and Kidney Cancer.
Dr Manish Patel MB.BS., MMed., FRACS Urological Oncologist Westmead Hospital & Westmead Private Hospital Senior Lecturer and Director of Urology – University of Sydney Scientific Director-Urological Cancer Organisation Urologist to the NSW Cancer Council


3 Bladder Cancer Incidence is Decreasing in NSW

4 Risk Factors Smoking Previous urothelial cancer.
Exposure to carcinogens Aromatic amines Benzedine Alanine dyes Urinary stasis (eg. Diverticulum) Chronic infection/irritation (eg. IDC, stone, UTIs)

5 Bladder Cancer Staging
Tis Superficial Invasive

6 Bladder Cancer Cell Types
Transitional Cell Carcinoma (TCC) >90% 70% are superficial Squamous Cell Carcinoma 5% Adenocarcinoma %

7 Progression of Urothelial Cancers
P53/ INK4A mutations Normal Urothelium Hyperplasia Chromosome 9 Papillary High Grade P53/ INK4A mutations CIS >40% 80% Progression Papillary Low Grade <4% Muscle Invasive

8 Cancer of the Bladder Signs and Symptoms
Percent of All Patients Painless Hematuria 85 Vesical Irritability 40 Flank pain or Kidney Failure 20 Lower extremity swelling 10 Pelvic Mass 10 Weight Loss 8 Abdominal or Bone Pain 5



11 Screening For Bladder Cancer Haematuria screening.
Haematuria does preceed a diagnosis for bladder cancer by >2 years. Cystoscopy is often negative in these early cases. However: In randomised studies of screening for haematuria, no benefit has been demonstrated in survival from bladder cancer.

12 Cystoscopy, cytology, and urinalysis together do not detect 100% of all bladder cancers. This, coupled with a desire to avoid the need for frequent cystoscopy to detect recurrences, has led to the investigation of new urine-based bladder cancer tests and various tumor markers to aid in detection and monitoring of bladder cancer. This slide provides a summary of the average sensitivity and specificity of the various urine tests in detecting transitional cell carcinoma (TCC). Several of them (indicated with an asterisk) are approved by the US Food and Drug Administration. The majority of these tests are more sensitive, but less specific, than urine cytology.1-3 High rates of false-positive results have limited their use as single markers. References 1. El-Gabry EA, Strup SE, Gomella LG. Superficial Bladder Cancer—Current Treatment Modalities and Future Directions. Parts I & II, AUA Update Series #20. Houston, Tex: American Urological Association, Office of Education; 2000. 2. Mian C, Pycha A, Wiener H, Haitel A, Lodde M, Marberger M. Immunocyt: a new tool for detecting transitional cell cancer of the urinary tract. J Urol. 1999;161: 3. Halling KC, King W, Dokolova IA, et al. A comparison of BTA stat, hemoglobin dipstick, telomerase and Vysis Urovysion assays for the detection of urothelial carcinoma in urine. J Urol. 2002;167:

13 Algorithm for Bladder Cancer Treatment

14 Instillation of BCG Reduces Recurrence and Progression of High Grade Bladder Cancers

15 Instillation of Single Dose Intravesical Chemotherapy Reduces Recurrences of Superficial Bladder Cancer

16 Early Cystectomy for Patients with HG Bladder Cancer Refractory to Intravesical Treatments Improves Survival

17 Extended Lymphadenectomy At Radical Cystectomy Improves Survival

18 Greater Number of Lymph Nodes Retrieved Results In Greater Survival

19 The Quality of Surgery Affects Survival

20 The Nerve Sparing Cystectomy
For the preservation of erectile function. Similar principles to the preservation of cavernous nerves during radical prostatectomy. Only possible in selected patients. Pioneered at MSKCC and USC. Early results: up to 70% potency.

21 Improvements in Neobladder Results
Ureters Better QoL Day-time continence 96% Night-time= 82% Females=38% ISC Males=5% ISC Pouch Urethra


23 Outcomes Following Radical Cystectomy

24 Chemotherapy and Bladder Cancer
MVAC was the standard of care:- Very toxic Gemcitabine and Cisplatin shown to be equivalent:- much less toxic. Can give as Neoadjuvant or Adjuvant therapy to improve survival. In the metastatic setting, will improve survival.

25 Patterns of Recurrence: Invasive Disease
Site Risk Factors Median time Local P3/4=34%, LN+ve=32% 8-18 months Distant Bone Lung Liver P1/2=20% P3=60% P4=70% LN+ve=40% 90% recur in first 3 years. Upper Tracts Generally 2-4% Ureteral Ca= 30% 22-40 months Urethral 17% after RC 6% after neobladder Up to 45% if TCC in prostate 1-3 years

26 Follow up Schedule After Cystectomy
Evaluation Year 1 Year 2 Year 3-5 Year 6+ History+ Exam 3mthly 6mthly 12mthly CXR Abdo/Pelvic CT FBC/UEC LFT Urethral Wash Uppertract cytology

27 Other Considerations in FollowUp
Metabolic complications Hypochloraemic hypokalaemic metabolic acidosis. Vitamin B12 and bile acids Urolithiasis Pyelonephritis Preservation of upper tracts. Potency Support for stoma or self catheterisation. Psychological support.

28 Follow Up Schedule After Superficial Disease
Likely hood of progression Likelyhood of recurrence 1st Year 2-5 years 6+ years Low Grade 4% 90% 6 monthly if 1st check clear 6 monthly yearly High grade Ta=40% T1=52% 95% 3 monthly CIS >50%

29 Diagnosis, Treatment and Follow-Up of Kidney Cancer

30 The Incidence of Kidney Cancer is Increasing
3.1% of male Cancers and 2.4% of female cancers Approx 50% mortality in NSW.

31 SIZE MIGRATION Conventional RCC 1983-1997
8.3 7.8 7.1 6.6 Mean size (cm) 5.5 Year

32 Risk Factors General Smoking Obesity Haemodialysis ?Diabetes Mellitus
? Hypertension Genetic VHL Tuberous Sclerosis Burt-Hogg-Dube Familial Papillary Familial Leimyomatosis

33 Most Patients are Incidentally Diagnosed.
Relatively asymptomatic until large/advanced. 25% Metastases at presentation. Flank pain % Haematuria % Mass <5% Paraneoplastic 10% Paraneoplastic symptoms Anaemia 30% Weight loss 33% Fever 30% Hypercalcaemia 10% Hepatic Sx 5% Amyloidosis 5% Enteropathy 3% Myopathy 3%

34 MALIGNANT RENAL CELL NEOPLASMS HeidelbergClassified by Cytogenetics
Type Occurrence Features Conventional Clear Cell 69% Common, aggressive. VHL and familial. Papillary 14% Often multiple and bilateral Less aggressive. Assoc. T.S. Oncocytoma 12% Benign. Chromophobe 5% Less aggressive. Collecting Duct Rare Very aggressive. Medullary

35 Cyctic Masses Have Variable Risk of Harbouring Cancer: Bosniak Classification.
Bosniak II: Internal septations: <5% malignant. Bosniak III: Enhancing rim: 45% Malignant Bosniak IV: Solid enhancing areas, coarse calcification 95%-100% Malignant.

36 TNM Staging of Renal Cell Carcinomas
T T3b/c <7cm Renal Vein or IVC Confined to Kidney T T4 >7cm Outside Gerotas Fascia T3a N: Nodes involved Adrenal or Gerotas M: Distant Mets. Fat involved

37 Survival: Renal Cell Carcinomas
TNM Stage T1 T2 or T3a T3b/c, T4 N or M

38 The Work Up For A Patient With Suspected Kidney Mass
Haematuria: US+/- IVP Surgery Mass Localised Possible Cytoreduction Mass Incidental Imaging Staging: Chest XR/CT B.S. if high risk High Quality CT Abdomen +/- IV contrast Interferon Tx Metastatic Give Choices Pain/Mass Palliation Clinical Trial

39 Open Radical Nephrectomy
Pros Gold standard for cancer cure. Standard for large, complicated tumours. Least intraoperative complications. Improvements: Small, less invasive incision- lower complications. Cons Major operation with recovery period. Higher lung complications.

40 Laparoscopic Radical Nephrectomy
Pros Less pain Quicker recovery Lower lung complications Cons Higher intraoperative complications. Can not do large complicated tumours. New procedure- no L/T data. Less kidney conservation.

41 Partial Nephrectomy Preserves Renal Function
Preservation of renal function. Old age Recurrent tumours Kidney diseases. Hyperfiltration More difficult surgery Slightly higher complication rate. Small tumours

42 New Technologys for Kidney Cancer RF ablation and cryoablation
RF ablating or freezing tumours under CT guidance. Early results acceptable for small tumours Applicable to elderly with small tumours. Depends on tumour location. No L/T data

43 Treatment for Metastatic Disease is Poor
Kidney Cancer is Resistant to Chemotherapy and Radiotherapy. Interferon g- standard of care. 10-15% have temporary response. Cytoreduction (removal of primary tumour) Can improve survival 4-16months in patients with good performance status and soft tissue mets.

44 Future of Advanced Disease
Kidney Cancers are very vascular. Biological therapies aimed at the blood supply of tumours: Antibodies to VEGF Thalidomide Gene therapy Introduce normal genes which are defective in the cancer, to switch of the increased blood supply to these tumours.

45 *Worthwhile screening as amenable to surgical therapy
Recurrence Patterns Site Risk Symptoms Lung* 3-16%, 54% of all metastases. Cough, haemoptysis, dyspnea Bone 2-8%, 20% of all metastases. Back, hip rib pain. Brain <2%, 5% of all metastases. Neurologic symptoms. Liver* 4% LFTs, CTs Contralateral Kidney* 1-2% (usually new primary) Abdo CT. Local * Recurrence 10% Abdo CT, loin/back pain. *Worthwhile screening as amenable to surgical therapy

46 Follow Up Protocol Risk Group History+Exam FBC, UEC LFT, Ca CXR
Abdominal CT Low Yearly 2 yearly. Intermediate 6 monthly, then yearly after 2 years 2 yearly High 3 monthly for 2 years, then 6 monthly. 6 monthly for 2 years, then yearly.

47 Isolated Renal Fossa, Lung or Liver Recurrence
Surgical therapy 50% survival Medical therapy 14% survival No therapy 12% survival

48 Suite 3, 2 Redleaf Ave. Wahroonga NSW 2076 (Ph) 9924 1777
Dr Manish Patel Urological Oncologist Senior Lecturer, University of Sydney Suite 12a Westmead Private Hospital Westmead NSW 2145 (Ph) Suite 3, 2 Redleaf Ave. Wahroonga NSW 2076 (Ph)

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