Case StudyCase Study

72 year old previously fit man72 year old previously fit man

Smoker, hypertensionSmoker, hypertension

2 month history of haematuria2 month history of haematuria

InvestigationsInvestigationsflexible cystoscopy - bladder flexible cystoscopy - bladder tumourtumour

USS - kidneys normal, mass USS - kidneys normal, mass indenting bladderindenting bladder

Surgery - TURBT to muscleSurgery - TURBT to muscle

4 cm tumour posterior wall of 4 cm tumour posterior wall of bladderbladder

EUA - no mass palpableEUA - no mass palpable

T2 tumourT2 tumour

Staging:Staging:

CXR normalCXR normal

MRI abdo/pelvis - 4 cm posterior wall bladder MRI abdo/pelvis - 4 cm posterior wall bladder tumour confined to bladder; no nodes; no bone tumour confined to bladder; no nodes; no bone mets; liver, kidneys, spleen - normalmets; liver, kidneys, spleen - normal

Biochemistry normal except Alk Phos 350 (Biochemistry normal except Alk Phos 350 ())

FBC - Hb 12.1 WCC 4.8 Plt 351FBC - Hb 12.1 WCC 4.8 Plt 351

Further staging of raised Further staging of raised alkaline phosphatasealkaline phosphatase

Bone scan - Paget’s disease Bone scan - Paget’s disease right femur, no metsright femur, no mets

Treatment:Treatment:

Options: cystectomy or radiotherapy +/- Options: cystectomy or radiotherapy +/- neoadjuvant chemotherapyneoadjuvant chemotherapy

Surgery and radiotherapy equivalent Surgery and radiotherapy equivalent outcomesoutcomes

Neoadjuvant chemo 5% benefit in 5 year Neoadjuvant chemo 5% benefit in 5 year survivalsurvival

Patient wishes bladder preservation Patient wishes bladder preservation so referred for radiotherapyso referred for radiotherapy

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

Tolerates wellTolerates well

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

6 weeks - reaction settling6 weeks - reaction settling

Check cystoscopy 3 months – clearCheck cystoscopy 3 months – clear

CT scan 6 months - nodes in pelvis, no CT scan 6 months - nodes in pelvis, no other disease, bladder clearother disease, bladder clear

Referred to Medical Oncology for chemo Referred to Medical Oncology for chemo - ? 15% chance of cure with nodes only- ? 15% chance of cure with nodes only

Poor renal function, so entered Poor renal function, so entered into EORTC 30986 trial of into EORTC 30986 trial of gem/carbo vs CMVgem/carbo vs CMV

Shrinkage of nodesShrinkage of nodes

No scope for further radiothearpyNo scope for further radiothearpy

AnatomyAnatomy

PathologyPathology

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

OR?? OR??

ManagementManagement

Start by TURBT.Start by TURBT.

MRI? Or CT? When?.MRI? Or CT? When?.

PET??PET??

Bone scan.Bone scan.

Stage and PrognosisStage and Prognosis

StageStage TNMTNM 5-y. Survival5-y. Survival

00 Ta/TisTa/Tis NoMoNoMo >85%>85%

II T1T1 NoMoNoMo 65-75%65-75%

IIII T2a-b T2a-b NoMoNoMo 57%57%

IIIIII T3a-4aT3a-4a NoMoNoMo 31%31%

IVIV T4bT4b NoMoNoMo 24%24%

each Teach T N+MoN+Mo 14%14%

each Teach T M+M+ med. 6-9 Momed. 6-9 Mo

StagingStagingU C L . (Urothelium, CIS., U C L . (Urothelium, CIS., Lamina propria)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?

Superficial Superficial Bladder CancerBladder Cancer

Low Risk. Low Risk.

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

High Risk. High Risk.

Low Malignant Low Malignant PotentialPotential

Ta or T1, G1 and G2 Ta or T1, G1 and G2

TUR Followed by Single Installation

When?

High Malignant High Malignant PotentialPotential

Ta or T1 G3 & DCISTa or T1 G3 & DCIS

TUR Followed by BCG

Harland et al., 2005; Shelley et al., 2001)

Cystectomy

Any Role for Any Role for MaintenanceMaintenance

Maintenance Chemotherapy once monthly Maintenance Chemotherapy once monthly for one year? for one year?

Once Monthly for 6 months?Once Monthly for 6 months?

Follow-up Follow-up

Superficial Bladder Superficial Bladder CancerCancer

pTa, pT1, TispTa, pT1, Tis

Standard of care=intravesical Therapy Standard of care=intravesical Therapy

transurethral resectiontransurethral resection

Relapse rate:Relapse rate: 70%70%

adjuvant therapyadjuvant therapy

Superficial Bladder Superficial Bladder CancerCancer

Histological grading is importantHistological grading is important

G1G1 G2G2 G3G3

Relapse rateRelapse rate 42%42% 50%50% 80%80%

Progression rateProgression rate 2%2% 11%11% 45%45%

Superficial Bladder Superficial Bladder CancerCancer

Adjuvant TherapyAdjuvant Therapy

Reduces relpase rate by 30-80%Reduces relpase rate by 30-80%

DoxorubicinDoxorubicin weekly 6-8 w. / weekly 6-8 w. / monthly 6-12monthly 6-12

Mitomycin CMitomycin C weekly 6-8 w. / weekly 6-8 w. / monthly 6-12monthly 6-12

BCGBCG weekly 6-8 w. /Mo 3 and 6 weekly 6-8 w. /Mo 3 and 6

RadiotherapyRadiotherapyNo RT in CIS??No RT in CIS??

T1 G3??T1 G3??

BCGBCGThe aim of treatment is to deliver 10 The aim of treatment is to deliver 10 000 000 organisms per instillation in 000 000 organisms per instillation in 50 ml of normal saline 2 to 4 weeks 50 ml of normal saline 2 to 4 weeks post TURBT.post TURBT.

3shan khatry 2 to 4 Weeks post TUR

NO BCG NO BCG

Immunosuppression.Immunosuppression.

Frank haematuria .Frank haematuria .

Bacterial infection.Bacterial infection.

Hepatic Insufficiency.Hepatic Insufficiency.

BCG Effectiveness BCG Effectiveness Principle therapy for Principle therapy for carcinoma in carcinoma in situ with a 60-80 percent CR (average situ with a 60-80 percent CR (average 76%) 76%)

Eradication of residual papillary Eradication of residual papillary disease in 45 to 60 percent of cases. disease in 45 to 60 percent of cases.

• • Effective prophylactic agent in Effective prophylactic agent in decreasing recurrence 20-65% (average decreasing recurrence 20-65% (average 40%). 40%).

• • Durability of response is an issue: Durability of response is an issue: 50-60% at 4 years and 30% at 10 50-60% at 4 years and 30% at 10 years.years.

Invasive Bladder Invasive Bladder CancerCancer

T2 and HigherT2 and Higher

Radical Radical CystectomyCystectomy

Remove What??? Remove What???

Don’t forget Lymphadenectomy.Don’t forget Lymphadenectomy.

Types of Surgery: Types of Surgery:

A- Ileal Conduit.A- Ileal Conduit.

B- Orthotopic neoBladder.B- Orthotopic neoBladder.

C-Continent Urinary diversion. C-Continent Urinary diversion.

Neoadjuvant Neoadjuvant ChemotherapyChemotherapy

Several randomised trials Several randomised trials and two Metaanalyses that the addition of and two Metaanalyses that the addition of neoadjuvant chemotherapy to either neoadjuvant chemotherapy to either cystectomy or radiotherapy provides a modest cystectomy or radiotherapy provides a modest overall survival benefit of around 5%.overall survival benefit of around 5%.

(Advanced Bladder Cancer Meta-analysis Collaboration, (Advanced Bladder Cancer Meta-analysis Collaboration, 2003 and 2005; Grossman et al., 2003; International 2003 and 2005; Grossman et al., 2003; International Collaboration of Trialists, 1999; McLaren, 2005; Winquist et Collaboration of Trialists, 1999; McLaren, 2005; Winquist et al., 2004)al., 2004)

Adjuvant Adjuvant ChemotherapyChemotherapy

Radical RadiotherapyRadical 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 Complete response with chemotherapy.chemotherapy.

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TREATMENT PLANNINGTREATMENT PLANNING

Radical Radiotherapy (Alone)Radical Radiotherapy (Alone)- Preparation.Preparation.

- Positioning. Positioning.

- Immobilization.Immobilization.

- Empty Bladder? Full Bladder? Why?Empty Bladder? Full Bladder? Why?

- Rectum? empty? Full. Rectum? empty? Full.

-

One half-hour prior to simulation, the One half-hour prior to simulation, the patient may be given an oral contrast patient may be given an oral contrast to drink so that the small bowel can be to drink so that the small bowel can be adequately visualized during the adequately visualized during the simulation process.simulation process.

When the regional lymph nodes are to be When the regional lymph nodes are to be covered for the initial 4500 cGy of covered for the initial 4500 cGy of treatment, some recommend that the treatment, some recommend that the patient be treated prone on a belly patient be treated prone on a belly board, with the bladder fully distended board, with the bladder fully distended (not in Nemrock) (not in Nemrock)

Foley catheter is inserted into the Foley catheter is inserted into the bladder with a sterile technique. Pull it bladder with a sterile technique. Pull it down so that you identify the bladder down so that you identify the bladder base.base.

A solution of Urographine mixed with A solution of Urographine mixed with saline in a one to two ratio is then saline in a one to two ratio is then instilled into the bladder. Generally, 25 instilled into the bladder. Generally, 25 cc of this mixture is instilled. Subsequcc of this mixture is instilled. Subsequ

Approximately 25 cc of air is also Approximately 25 cc of air is also injected into the bladder and the Foley injected into the bladder and the Foley catheter is clamped.catheter is clamped.

3Shan Khatry OUL LLMARYDE HAWA will 3Shan Khatry OUL LLMARYDE HAWA will come out during urine voidingcome out during urine voiding

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

Rectal tube with barium (25cc paste in Rectal tube with barium (25cc paste in 25cc water).25cc water).

SHOULD BE AT THE END SHOULD BE AT THE END DURING LAT SIM FILM ONLY DURING LAT SIM FILM ONLY

Why High Energy?Why High Energy?

Why High Energy?Why High Energy?

BordersBorders

Upper:Upper:

Lower:Lower:

Anterior.Anterior.

Posterior.Posterior.

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

BoostBoostBladder with a Margin. Bladder with a Margin.

Palliative RTPalliative RT

A randomised trial has shown similar A randomised trial has shown similar palliation rates with a short, palliation rates with a short, hypofractionated treatment (21 Gy in hypofractionated treatment (21 Gy in 3 fractions) as with a higher dose 3 fractions) as with a higher dose palliative treatment (35 Gy in 10 palliative treatment (35 Gy in 10 fractions).fractions).

30Gy in 10 TTT still acceptable. 30Gy in 10 TTT still acceptable.

(Duchesne (Duchesne et al., 2000). et al., 2000).

Phase 1Phase 1

PTV:PTV: Bladder with 2cm ?HD margin, Bladder with 2cm ?HD margin, pelvic nodes.pelvic nodes.

DLS:DLS: Femoral necks (limit to 45), Femoral necks (limit to 45), posterior rectumposterior rectum

(limit to 60)(limit to 60)

Energy:Energy: 10-18 MV 10-18 MV

SimAids: Cystogram is done: Patient voids SimAids: Cystogram is done: Patient voids completely. Foley catheter inserted, 7cc put completely. Foley catheter inserted, 7cc put in foley balloon. Residual measured. Equal in foley balloon. Residual measured. Equal amount of contrast dye (>=25cc) injected into amount of contrast dye (>=25cc) injected into bladder, along with 10cc of air. Foley bladder, along with 10cc of air. Foley clamped. After sim, foley allowed to drain, clamped. After sim, foley allowed to drain, then removed. then removed.

Fields: 4 field box used. AP-PA borders are: Fields: 4 field box used. AP-PA borders are: Sup= L5/S1, Inf= bottom of obt foramen, Lat= Sup= L5/S1, Inf= bottom of obt foramen, Lat= 1½cm beyond pelvic brim. If prostate 1½cm beyond pelvic brim. If prostate involvement, Inf = bottom of isch tub.involvement, Inf = bottom of isch tub.

For Lats, Ant= 3cm beyond contrast in For Lats, Ant= 3cm beyond contrast in bladder (1cm bladder wall thickness + 2cm bladder (1cm bladder wall thickness + 2cm margin). This is anterior to the symphysis. margin). This is anterior to the symphysis. Try to avoid skin splash-over. Post= 3cm Try to avoid skin splash-over. Post= 3cm behind contrast, i.e. ~ S1/S2 junction.behind contrast, i.e. ~ S1/S2 junction.

BMD: Shielding on the APPA over femoral BMD: Shielding on the APPA over femoral heads, +/- upper corners. Shielding on the heads, +/- upper corners. Shielding on the lats under the symphysis.lats under the symphysis.

Prescription: 4500/25 to isocentre.Prescription: 4500/25 to isocentre.

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TREATMENT PLANNINGTREATMENT PLANNING

Radical Radiotherapy (Alone)Radical Radiotherapy (Alone)

Phase 2Phase 2

TV is bladder with 2 cm HD margin. Repeat TV is bladder with 2 cm HD margin. Repeat cystogram. 4 field box. Use 2½cm margins cystogram. 4 field box. Use 2½cm margins beyond the intravesical dye in all beyond the intravesical dye in all directions. Use diagnostic CT in directions. Use diagnostic CT in conjunction to estimate bladder wall conjunction to estimate bladder wall thickness. Prescription is 1980/11.thickness. Prescription is 1980/11.

Or, can boost tumor alone with 2 cm margins. Or, can boost tumor alone with 2 cm margins. You need an accurate bladder tumor map plus You need an accurate bladder tumor map plus a pre-treatment CT scan for this. Ideally, a pre-treatment CT scan for this. Ideally, you should be present at the cystoscopy. you should be present at the cystoscopy. Sim with full bladder and use lateral POP.Sim with full bladder and use lateral POP.

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Poor candidate for bladder Poor candidate for bladder preservationpreservation

Small volume bladder after several Small volume bladder after several intravasical BCGintravasical BCG

Large atonic bladder with DiverticulaeLarge atonic bladder with Diverticulae

Diffuse multifocal involvement of the Diffuse multifocal involvement of the bladder mucosabladder mucosa

PID , IBD & previous surgery with adhesionsPID , IBD & previous surgery with adhesions

Suboptimal bladder function (incontenance& Suboptimal bladder function (incontenance& sever urgency)sever urgency)

Lage T4b with 5cm extravasical extension Lage T4b with 5cm extravasical extension with hydonephrosiswith hydonephrosis

CIS with squamous differentiation CIS with squamous differentiation