A Guide to the Diagnosis, Treatment and Follow-Up of Bladder and Kidney Cancer.

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 0.5-2%

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 BladderSigns and Symptoms 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 CancerHaematuria 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.

13. Algorithm for Bladder Cancer Treatment Chemotherapy

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

25. Patterns of Recurrence:Invasive Disease

26. Follow up Schedule After Cystectomy

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

29. Diagnosis, Treatment and Follow-Up ofKidney 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 MIGRATIONConventional RCC 1983-1997 8.3 7.8 7.1 6.6 Mean size (cm) 5.5 Year

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

33. Relatively asymptomatic until large/advanced. 25% Metastases at presentation. Flank pain 10-30% Haematuria 50% Mass <5% Paraneoplastic 10% Paraneoplastic symptoms Anaemia 30% Weight loss 33% Fever 30% Hypercalcaemia 10% Hepatic Sx 5% Amyloidosis 5% Enteropathy 3% Myopathy 3% Most Patients are Incidentally Diagnosed.

34. MALIGNANT RENAL CELL NEOPLASMSHeidelbergClassified by Cytogenetics

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 T1 T3b/c <7cm Renal Vein or IVC Confined to Kidney T2 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 Staging: Chest XR/CT B.S. if high risk Incidental Imaging High Quality CT Abdomen +/- IV contrast Interferon Tx Metastatic Give Choices Pain/Mass Palliation Clinical Trial

39. 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. Open Radical Nephrectomy

40. 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. Laparoscopic Radical Nephrectomy

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 CancerRF 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. Recurrence Patterns *Worthwhile screening as amenable to surgical therapy

46. Follow Up Protocol

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

48. Dr Manish PatelUrological OncologistSenior Lecturer, University of Sydney Suite 12a Westmead Private Hospital Westmead NSW 2145 (Ph) 9633 2088 Suite 3, 2 Redleaf Ave. Wahroonga NSW 2076 (Ph) 9924 1777