Can We Preserve The Bladder InCan We Preserve The Bladder InMuscle Invasive Bladder Cancer?Muscle Invasive Bladder Cancer?

Dr Manish PatelDr Manish Patel Urological Cancer Surgeon Urological Cancer Surgeon

Westmead HospitalWestmead HospitalUniversity of SydneyUniversity of Sydney

The Outcomes of Radical CystectomyThe Outcomes of Radical Cystectomy• Outcomes of RC are

very good.• Recurrences occur:• Median 12 months• 86% of recurrences

occur in first 3 years.• Local only recurrence

more likley in OC.• Most series- any

recurrence= death.• Even with LN+ve

disease, 30% likelihood of long term survival.

Stein et.al. Journal of Clinical Oncology, Vol 19, No 3 (February 1), 2001: pp 666-675

Upstaging is common with Bladder CancerUpstaging is common with Bladder Cancer• Based on TURBT, EUA, CT

– MRI with dynamic contrast enhancement and Fe particles may be better.

– Ureteric obstruction- 67%-90% >pT2 (Skinner et,al,1998)

• Muscle invasive bladder cancer (cT2) is upstaged to pT3 in:

– 52% (Soloway et.al.1994)

– 78% (Pagano et.al.1991)

– 41% (Frazier et.al.1992)

Most cT2 bladder cancers are pT3 or higher.

• Occult LN mets increase with increasing P stage

– P0, Pa, Pis, P1: 5%

– P2: 18-27%

– P3-4: 45%

Quality of Life After RC is Good.Quality of Life After RC is Good.• There are a number of QoL instruments for bladder cancer.

• Very few reports on QoL after BC treatment.

• Lack of baseline measurements.

• Lack of longitudinal measurements.

• No comparison of RC vs Bladder Preservation.

Only on prospective QoL study (SF-36) (Hardt et.al)

Physical functioning decreased pre-post-op (80 to 68)

Pain, health perception, vitality, social functioning, general well being, satisfaction with life all the same as pre-op at one year.

Options of Bladder Preservation with Options of Bladder Preservation with Muscle Invasive BCMuscle Invasive BC

• TURBT alone• Partial Cystectomy alone• External Beam Radiation Alone• Brachytherapy• Neoadjuvant Chemo and TURBT• Neoadjuvant Chemo and Partial cystectomy• Multimodality therapy

Does a delay in cystectomyDoes a delay in cystectomy Result in lower survival? Result in lower survival?

• Randomised studies of immediate cystectomy vs XRT and salvage cystectomy.

Study Randomised groups Survival

MD Andersen (n=67)

Immediate XRT+cystectomy 5yrs: 45%

XRT and salvage cystectomy 5yrs: 22%

Urologic Co-operative Group UK (n=187)

Immediate cystectomy 5 yrs: 39%

XRT with salvage surgery 5 yrs: 29%

Danish National Bladder Group (n=187)

Immediate XRT+cystectomy 5 yrs: 29%

XRT and salvage cystectomy 5 yrs: 23%

Possibly: Need low threshold for salvage cystectomyPossibly: Need low threshold for salvage cystectomy

TURBTTURBT

• TURBT is feasible for selected T2 bladder tumours.TURBT is feasible for selected T2 bladder tumours.• Not for dome or high posterior wall

Author Protocol Survival Cystectomy rate

Barnes (n=85) G1/2 T2TURBT X1

27% 5 yrs

Henry (n=43) Favourable (small T2) TURBT X1

77% 5 yrs 25%

Solsona (n=59) Negative cytology and rpt biopsy

83% @4 yrs 19%

Herr (n=45) Negative rpt TUR and cytology

82% @ 5 yrs 24%

Partial CystectomyPartial CystectomyMSKCC study (contemporary)

• 85 patients with T2

• OS: 69% @ 5yrs

• 74% alive with bladder intact

• 67% alive with NED bladder intact

• 7 pts sup recurrence

• 15 pts advanced recurrence

– 75% false negative frozen section margins.

– 80% of positive margins suffered advanced recurrence.

• Selection:

• Dome/post wall/diverticulum

Partial CystectomyPartial Cystectomy

• Candidates:– CR or PR to

Neoadjuvant chemo

– Solitary lesions in favoyrable locations

– No CIS

– Good bladder capacity.

RadiationRadiationStudy Patient no. Survival (5 yr%)

T2 T3

Fossa et.al. 308 38 14

Davidson et.al 709 49 28

Gospodarowicz 355 50 32

Goffinet et.al. 384 42 35

•TURBT and 65 Gy XRT•Tumour debulking (TURBT may be most important)•Assessment of response at 40Gy may be useful•CR to XRT- will have a good outcome.•60% invasive recurrence rate. Approx 50% cystectomy rate. •Co-existant CIS: High recurrence rate in bladder (70%).•Squamous differentiation may have poorer outcome

Radiation-ComplicationsRadiation-Complications

Early complications

• Diarrhea

• Bladder irritation (particularly if trigonal cancers)

Late complications (2-3 years later)

• Worse if heavily pretreated (TURBTS, BCG etc)

• Radiation cystitis (heamturia, frequency contracted bladder)

• Radiation proctitis (persistent diarrhea, rectal bleeding)

• Sexual dysfunction (60%)

Tumour Recurrence

• Invasive – salvage cystectomy

• Superficial- as per normal protocols

Neoadjuvant and Partial cystectomyNeoadjuvant and Partial cystectomy• Neoadjuvant chemotherapy (X3-4 cycles) followed by TURBT

staging.

• Then followed by partial cystectomy and pelvic lymph node dissection.

• Herr et.al (n=26). No Pt was eligible for PC alone.

– 19 had P0

– 7 yr median FU: 65% alive

54% with bladder

18% invasive recurrence

26% superficial recurrence

PC is a valid option in suitable patients, even with T3 tumours that are small.

Neoadjuvant and TURBTNeoadjuvant and TURBT• Neoadjuvant chemo (3-4 cycles).

• Restaging TURBT.

• Stenberg et.al (n=71). T2-T4a

– Median 54 months FU: 71% alive

57% bladder intact

After chemo: P0 or superficial disease, 5yr survival = 71%

Invasive disease 29%

MSKCC (n=111)

60(54%) achieved T0 status.- Most preserved bladders

56% recurrence in bladder (30% invasive)

25% of T0 is not P0.

Neoadjuvant chemotherapy and TURBTNeoadjuvant chemotherapy and TURBT• Srougi et.al. (n=30)

• TURBT, MVACX3.

– PR or no response > cystectomy (n=12)

– CR > all retained their bladder (n=14)

• 5 yrs, 71% (10) had local recurrences.

– 8 had radical cystectomy

• Survival of all CR pts was 79% @ 5yrs.

• All patients need close observation because of inadequate staging All patients need close observation because of inadequate staging and occurrence of new tumours.and occurrence of new tumours.

Trimodality TherapyTrimodality Therapy• Maximal TURBT

• XRT

• Concurrent chemotherapy

• Rational

– Cisplatin, 5-FU and paclitaxel sensitise tumour tissues to XRT.

– Increase cell kill in a synergisitic fashion.

– Also high (25%-50%) chance of micro-metastatic disease at presentation.

Does the radiation add anything, as XRT outcomes are similar to TURBT outcomes?

Trimodality TherapyTrimodality Therapy

SeriesSeries TreatmentTreatment 5 yr 5 yr survivalsurvival

5 yr survival 5 yr survival with bladderwith bladder

TURBT, XRT and concurrent Chemotherapy.TURBT, XRT and concurrent Chemotherapy.

Dunst (n=79) TURBT, cisplatin, XRT 52% 41%

RTOG 1993 (n=42) Cisplatin and XRT 52% 42%

Kachnic (n=106) TURBT, MCV and XRT 52% 43%

RTOG 1997 (n=123) TURBT, MCV and XRT 49% 38%

TURBT and Chemotherapy aloneTURBT and Chemotherapy alone

Given (n=93) TURBT and MCV 51% 18%

Srougi (n=30) Partial C and MVAC 53% 20%

It appears that concurrent chemo/XRT does add something.It appears that concurrent chemo/XRT does add something.

Shipley- Massachusetts General ProtocolShipley- Massachusetts General ProtocolHydronephrosis, Poor renal function

Irritable bladder, Low Capacity

T4a/4b, CIS

If yes, For surgery

Radical Cystectomy

If no, Maximal TURBT

No Significant Tumour Remaining

Bulky Tumour Remaining

Chemo/ XRTProtocol-Induction

CE 4 weeks after induction

CR, consolidationChemoradiation

Residual Cancer

MGH- Chemoradiation ProtocolMGH- Chemoradiation Protocol• Induction

• 2 cycles of neoadjuvant MCV

– Methotrexate, cisplatin, vinblastine

• Concurrent cisplatin and 40Gy XRT

• Consolidation chemoradiation

• Further 24Gy XRT

• Cisplatin based chemotherapy

MGH- ResultsMGH- Results• Patients selected for Trimodality therapy (n=190)

– Denominator unknown

• Induction chemotherapy

– 29 (15%) had residual disease > RC

– 40 (21%) unable to tolerate ChemoRad > RC

• 121 (64%) went on to have consolidation Chemoradiation.

• After 4 years median FU

– 86 (45%) alive with NED

– 110 (58%) still had a bladder.

• Overall survival @ 5 yrs 54%

RTOG bladder sparing protocolsRTOG bladder sparing protocols

• All tumours are small.

• All tumours are able to be maximally resected.

• These are not the same tumours in cystectomy series.These are not the same tumours in cystectomy series.

• All patients are healthy with good ECOG status

• All patients were eligible for cystectomy.

Clinical Preictors of OutcomeClinical Preictors of Outcome• Stage (cT2=62%, cT3=47%)

• Hydronephrosis (CR= 37% vs 68%)

• CR on induction chemoradiation

Quality of Life

• Cystectomy for bladder contracture (2-7%)

• On going urinary symptoms

• Women-19% incontinence

• Reduced urinary compliance in 22%

• Bowel symptoms- 22%

• Sexual dysfunction

Concerns with Bladder sparing therapyConcerns with Bladder sparing therapy• Need for complete TURBT (visibly clear)

– CR 77% vs 54% for visble and not visible complete resection.

– Survival 52% vs 34% @ 5 yrs

• Urothelial cancer change

– Those with CR to trimodality will develop

– 20-30% new or recurrent bladder tumor

– Occur median of 2.1 years and mainly CIS

– Ultimately 1/3 of recurrence need late cystectomy.

• Pelvic recurrence

– 12%

• Delay in cystectomy

• Limited diversion alternatives.

Is Bladder Preservation Equivalent to Is Bladder Preservation Equivalent to Radical Cystectomy?Radical Cystectomy?

• No but!

• Viable alternative for Pts wanting to preserve bladder

• Only small likely decrease in survival

• But

• Not all patients are suitable

• 50% will ultimately have cystectomy

– Diversion choices will be limited.

– Operation more difficult and complications higher.

• Not evidence that quality of life is actually better.

• A number of pts will have significant bladder and bowel symptoms.