2. Case Study 72 year old previously fit man 72 year old previously fit man Smoker, hypertension Smoker, hypertension 2 month history of haematuria 2 month history of haematuria Investigations Investigations flexible cystoscopy - bladder tumour flexible cystoscopy - bladder tumour USS - kidneys normal, mass indenting bladder USS - kidneys normal, mass indenting bladder

3. Surgery - TURBT to muscle Surgery - TURBT to muscle 4 cm tumour posterior wall of bladder 4 cm tumour posterior wall of bladder EUA - no mass palpable EUA - no mass palpable T2 tumour T2 tumour

4. Staging: CXR normal CXR normal MRI abdo/pelvis - 4 cm posterior wall bladder tumour confined to bladder; no nodes; no bone mets; liver, kidneys, spleen - normal MRI abdo/pelvis - 4 cm posterior wall bladder tumour confined to bladder; no nodes; no bone mets; liver, kidneys, spleen - normal Biochemistry normal except Alk Phos 350 (  ) Biochemistry normal except Alk Phos 350 (  ) FBC - Hb 12.1 WCC 4.8 Plt 351 FBC - Hb 12.1 WCC 4.8 Plt 351

5. Further staging of raised alkaline phosphatase Further staging of raised alkaline phosphatase Bone scan - Paget’s disease right femur, no mets Bone scan - Paget’s disease right femur, no mets

6. Treatment: Options: cystectomy or radiotherapy +/- neoadjuvant chemotherapy Options: cystectomy or radiotherapy +/- neoadjuvant chemotherapy Surgery and radiotherapy equivalent outcomes Surgery and radiotherapy equivalent outcomes Neoadjuvant chemo 5% benefit in 5 year survival Neoadjuvant chemo 5% benefit in 5 year survival

7. Patient wishes bladder preservation so referred for radiotherapy Patient wishes bladder preservation so referred for radiotherapy

8. XRT alone 55 Gy in 20 fractions (4 week wait) XRT alone 55 Gy in 20 fractions (4 week wait)

9. Tolerates well Tolerates well Tiredness, diarrhoea/proctitis (fybogel), dysuria (2 litres fluids per day, cranberry juice) Tiredness, diarrhoea/proctitis (fybogel), dysuria (2 litres fluids per day, cranberry juice)

10. 6 weeks - reaction settling 6 weeks - reaction settling Check cystoscopy 3 months – clear Check cystoscopy 3 months – clear CT scan 6 months - nodes in pelvis, no other disease, bladder clear CT scan 6 months - nodes in pelvis, no other disease, bladder clear Referred to Medical Oncology for chemo - ? 15% chance of cure with nodes only Referred to Medical Oncology for chemo - ? 15% chance of cure with nodes only

11. Poor renal function, so entered into EORTC 30986 trial of gem/carbo vs CMV Poor renal function, so entered into EORTC 30986 trial of gem/carbo vs CMV Shrinkage of nodes Shrinkage of nodes No scope for further radiothearpy No scope for further radiothearpy

12. Anatomy

13. Pathology Adenocarcinomas are extremely rare. There are occasionally seen in the dome of the bladder, where they are thought to originate from a persistent urachus, but they may also occur around the trigone (possibly originating from cystic glandularis). Adenocarcinomas are extremely rare. There are occasionally seen in the dome of the bladder, where they are thought to originate from a persistent urachus, but they may also occur around the trigone (possibly originating from cystic glandularis). OR?? OR??

14. Management Start by TURBT. Start by TURBT. MRI? Or CT? When?. MRI? Or CT? When?. PET?? PET?? Bone scan. Bone scan.

15. Stage and Prognosis StageTNM5-y. Survival 0Ta/TisNoMo>85% IT1NoMo65-75% IIT2a-b NoMo57% IIIT3a-4aNoMo31% IVT4bNoMo24% each TN+Mo14% each TM+med. 6-9 Mo

16. Staging U C L. (Urothelium, CIS., Lamina propria) U C L. (Urothelium, CIS., Lamina propria) Inner and Outer (detrusal). Inner and Outer (detrusal). Peri micro. Peri micro. Peri gross. Peri gross. Extension a or b. Extension a or b. Nodal Disease?

20. Superficial Bladder Cancer Low Risk of Progression Low Malignant potential High Risk of Progression High Malignant Potential

21. Low Risk. Low Risk. Intermediate Risk (multifocal T1G1, TaG2 and single T1G2 tumours). Intermediate Risk (multifocal T1G1, TaG2 and single T1G2 tumours). High Risk. High Risk.

22. Low Malignant Potential Ta or T1, G1 and G2 Ta or T1, G1 and G2 TUR Followed by Single Installation When?

23. High Malignant Potential Ta or T1 G3 & DCIS TUR Followed by BCG Harland et al., 2005; Shelley et al., 2001) Cystectomy

24. Any Role for Maintenance Maintenance Chemotherapy once monthly for one year? Maintenance Chemotherapy once monthly for one year? Once Monthly for 6 months? Once Monthly for 6 months?

25. Follow-up

28. Superficial Bladder Cancer pTa, pT1, Tis Standard of care=intravesical Therapy Standard of care=intravesical Therapy  transurethral resection Relapse rate:70% Relapse rate:70%  adjuvant therapy

29. Superficial Bladder Cancer Histological grading is important Histological grading is important G1G2G3 Relapse rate42%50%80% Progression rate2%11%45%

30. Superficial Bladder Cancer Adjuvant Therapy Reduces relpase rate by 30-80% Reduces relpase rate by 30-80% Doxorubicinweekly 6-8 w. / monthly 6-12 Doxorubicinweekly 6-8 w. / monthly 6-12 Mitomycin C weekly 6-8 w. / monthly 6-12 Mitomycin C weekly 6-8 w. / monthly 6-12 BCG weekly 6-8 w. /Mo 3 and 6 BCG weekly 6-8 w. /Mo 3 and 6

31. Radiotherapy No RT in CIS?? No RT in CIS?? T1 G3?? T1 G3??

32. BCG The aim of treatment is to deliver 10 000 000 organisms per instillation in 50 ml of normal saline 2 to 4 weeks post TURBT. The aim of treatment is to deliver 10 000 000 organisms per instillation in 50 ml of normal saline 2 to 4 weeks post TURBT. 3shan khatry 2 to 4 Weeks post TUR

33. NO BCG Immunosuppression. Immunosuppression. Frank haematuria. Frank haematuria. Bacterial infection. Bacterial infection. Hepatic Insufficiency. Hepatic Insufficiency.

34. BCG Effectiveness Principle therapy for carcinoma in situ with a 60-80 percent CR (average 76%) Principle therapy for carcinoma in situ with a 60-80 percent CR (average 76%) Eradication of residual papillary disease in 45 to 60 percent of cases. Eradication of residual papillary disease in 45 to 60 percent of cases. Effective prophylactic agent in decreasing recurrence 20-65% (average 40%). Effective prophylactic agent in decreasing recurrence 20-65% (average 40%). Durability of response is an issue: 50-60% at 4 years and 30% at 10 years. Durability of response is an issue: 50-60% at 4 years and 30% at 10 years.

35. Invasive Bladder Cancer T2 and Higher

36. Radical Cystectomy Remove What??? Remove What??? Don’t forget Lymphadenectomy. Don’t forget Lymphadenectomy. Types of Surgery: Types of Surgery: A- Ileal Conduit. B- Orthotopic neoBladder. C-Continent Urinary diversion.

37. Neoadjuvant Chemotherapy

38. Several randomised trials Several randomised trials and two Metaanalyses that the addition of neoadjuvant chemotherapy to either cystectomy or radiotherapy provides a modest overall survival benefit of around 5%. (Advanced Bladder Cancer Meta-analysis Collaboration, 2003 and 2005; Grossman et al., 2003; International Collaboration of Trialists, 1999; McLaren, 2005; Winquist et al., 2004) (Advanced Bladder Cancer Meta-analysis Collaboration, 2003 and 2005; Grossman et al., 2003; International Collaboration of Trialists, 1999; McLaren, 2005; Winquist et al., 2004)

39. Adjuvant Chemotherapy

40. Radical Radiotherapy Younger patients with: Younger patients with: Small tumours. Small tumours. No ureteric obstruction. No ureteric obstruction. Complete resection at TURBT. Complete resection at TURBT. Complete response with chemotherapy. Complete response with chemotherapy.

41. 41 TREATMENT PLANNING Radical Radiotherapy (Alone) Radical Radiotherapy (Alone) -Preparation. -Positioning. -Immobilization. -Empty Bladder? Full Bladder? Why? -Rectum? empty? Full. -

42. One half-hour prior to simulation, the patient may be given an oral contrast to drink so that the small bowel can be adequately visualized during the simulation process. One half-hour prior to simulation, the patient may be given an oral contrast to drink so that the small bowel can be adequately visualized during the simulation process. When the regional lymph nodes are to be covered for the initial 4500 cGy of treatment, some recommend that the patient be treated prone on a belly board, with the bladder fully distended (not in Nemrock) When the regional lymph nodes are to be covered for the initial 4500 cGy of treatment, some recommend that the patient be treated prone on a belly board, with the bladder fully distended (not in Nemrock)

43. Foley catheter is inserted into the bladder with a sterile technique. Pull it down so that you identify the bladder base. Foley catheter is inserted into the bladder with a sterile technique. Pull it down so that you identify the bladder base. A solution of Urographine mixed with saline in a one to two ratio is then instilled into the bladder. Generally, 25 cc of this mixture is instilled. Subsequ A solution of Urographine mixed with saline in a one to two ratio is then instilled into the bladder. Generally, 25 cc of this mixture is instilled. Subsequ Approximately 25 cc of air is also injected into the bladder and the Foley catheter is clamped. Approximately 25 cc of air is also injected into the bladder and the Foley catheter is clamped. 3Shan Khatry OUL LLMARYDE HAWA will come out during urine voiding

44. Marker on External Anal Canal. Marker on External Anal Canal.

45. Rectal tube with barium (25cc paste in 25cc water). Rectal tube with barium (25cc paste in 25cc water). SHOULD BE AT THE END DURING LAT SIM FILM ONLY

46. Why High Energy?

48. Borders Upper: Upper: Lower: Lower: Anterior. Anterior. Posterior. Posterior.

52. The anterior border on the lateral field is defined by a line extending from the tip of the pubic symphysis to a point 2.5 cm anterior to the bony sacral promontory. The anterior border on the lateral field is defined by a line extending from the tip of the pubic symphysis to a point 2.5 cm anterior to the bony sacral promontory.

53. Boost Bladder with a Margin. Bladder with a Margin.

54. Palliative RT A randomised trial has shown similar palliation rates with a short, hypofractionated treatment (21 Gy in 3 fractions) as with a higher dose palliative treatment (35 Gy in 10 fractions). A randomised trial has shown similar palliation rates with a short, hypofractionated treatment (21 Gy in 3 fractions) as with a higher dose palliative treatment (35 Gy in 10 fractions). 30Gy in 10 TTT still acceptable. 30Gy in 10 TTT still acceptable. (Duchesne et al., 2000).

55.  Phase 1 PTV: Bladder with 2cm ?HD margin, pelvic nodes. PTV: Bladder with 2cm ?HD margin, pelvic nodes. DLS: Femoral necks (limit to 45), posterior rectum DLS: Femoral necks (limit to 45), posterior rectum (limit to 60) (limit to 60) Energy: 10-18 MV Energy: 10-18 MV

56. SimAids: Cystogram is done: Patient voids completely. Foley catheter inserted, 7cc put in foley balloon. Residual measured. Equal amount of contrast dye (>=25cc) injected into bladder, along with 10cc of air. Foley clamped. After sim, foley allowed to drain, then removed. SimAids: Cystogram is done: Patient voids completely. Foley catheter inserted, 7cc put in foley balloon. Residual measured. Equal amount of contrast dye (>=25cc) injected into bladder, along with 10cc of air. Foley clamped. After sim, foley allowed to drain, then removed. Fields: 4 field box used. AP-PA borders are: Sup= L5/S1, Inf= bottom of obt foramen, Lat= 1½cm beyond pelvic brim. If prostate involvement, Inf = bottom of isch tub. Fields: 4 field box used. AP-PA borders are: Sup= L5/S1, Inf= bottom of obt foramen, Lat= 1½cm beyond pelvic brim. If prostate involvement, Inf = bottom of isch tub. For Lats, Ant= 3cm beyond contrast in bladder (1cm bladder wall thickness + 2cm margin). This is anterior to the symphysis. Try to avoid skin splash-over. Post= 3cm behind contrast, i.e. ~ S1/S2 junction. For Lats, Ant= 3cm beyond contrast in bladder (1cm bladder wall thickness + 2cm margin). This is anterior to the symphysis. Try to avoid skin splash-over. Post= 3cm behind contrast, i.e. ~ S1/S2 junction. BMD: Shielding on the APPA over femoral heads, +/- upper corners. Shielding on the lats under the symphysis. BMD: Shielding on the APPA over femoral heads, +/- upper corners. Shielding on the lats under the symphysis. Prescription: 4500/25 to isocentre. Prescription: 4500/25 to isocentre.

57. 57 TREATMENT PLANNING Radical Radiotherapy (Alone) Radical Radiotherapy (Alone) Phase 2 Phase 2 TV is bladder with 2 cm HD margin. Repeat cystogram. 4 field box. Use 2½cm margins beyond the intravesical dye in all directions. Use diagnostic CT in conjunction to estimate bladder wall thickness. Prescription is 1980/11. TV is bladder with 2 cm HD margin. Repeat cystogram. 4 field box. Use 2½cm margins beyond the intravesical dye in all directions. Use diagnostic CT in conjunction to estimate bladder wall thickness. Prescription is 1980/11. Or, can boost tumor alone with 2 cm margins. You need an accurate bladder tumor map plus a pre-treatment CT scan for this. Ideally, you should be present at the cystoscopy. Sim with full bladder and use lateral POP. Or, can boost tumor alone with 2 cm margins. You need an accurate bladder tumor map plus a pre-treatment CT scan for this. Ideally, you should be present at the cystoscopy. Sim with full bladder and use lateral POP.

58. 58 Poor candidate for bladder preservation Small volume bladder after several intravasical BCG Small volume bladder after several intravasical BCG Large atonic bladder with Diverticulae Large atonic bladder with Diverticulae Diffuse multifocal involvement of the bladder mucosa Diffuse multifocal involvement of the bladder mucosa PID, IBD & previous surgery with adhesions PID, IBD & previous surgery with adhesions Suboptimal bladder function (incontenance& sever urgency) Suboptimal bladder function (incontenance& sever urgency) Lage T4b with 5cm extravasical extension with hydonephrosis Lage T4b with 5cm extravasical extension with hydonephrosis CIS with squamous differentiation CIS with squamous differentiation