Role of bladder preserving approach in the treatment of muscle invasive tcc
Download
1 / 69

Role of Bladder -Preserving Approach in The Treatment of Muscle Invasive TCC - PowerPoint PPT Presentation


  • 153 Views
  • Uploaded on
  • Presentation posted in: General

Role of Bladder -Preserving Approach in The Treatment of Muscle Invasive TCC. Introduction. Bladder cancer is a serious threat to life. TCC is the most common bladder tumor. For the yr 2000 (in US): 53,200 new cases 12,200 deaths. Introduction. TCC at the initial presentation.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha

Download Presentation

Role of Bladder -Preserving Approach in The Treatment of Muscle Invasive TCC

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Role of Bladder-Preserving ApproachinThe Treatment of Muscle Invasive TCC


Introduction

Bladder cancer is a serious threat to life.

TCC is the most common bladder tumor.

For the yr 2000 (in US):

53,200 new cases

12,200 deaths


Introduction

TCC at the initial presentation.

  • 70% of TCC are superficial

    • Tumor recurrence is 50-70%

      • 10-30% of those will progress to invasive disease.

  • 30% of TCC are muscle invasive

    • More than ½ of them expected to develop metz

      = 12,000 death/yr in the US

      = 50 –100 / 1,000,000


Introduction

Treatment of invasive TCC

  • Aggressive therapy is warranted to control the disease.

  • This shouldn’t obscure the need for reasonable quality of life.

  • In North America, main local management of muscle-invasive TCC remains radical cystectomy with urinary diversion.


Introduction

  • This approach is undergoing transition.

  • Organ-preserving approaches have been successfully applied to the management of several types of cancer

  • Clearly play an important role in the management of ms invasive TCC.


Introduction

  • Ideally, trt of invasive TCC aims to:

    • Eliminate the primary tumor.

    • Assure long term survival & quality of life.

    • Maintain normally functioning bladder.

  • In elderly or pts likely to die of other causes local control may be all what is needed.

  • So, reaching those goals & preserving the bladder may appear to be attractive option.

    • In minimal surgery, post op complications can be limited.


Introduction

Cystectomy & its Price for a Gold Stander

  • Major operation

  • Complication

    • Acknowledged mortality(although low).

      • 2.3%

    • 10-15% overall complication rate

    • Higher (20-30%) for orthotopic reconstruction.

  • (220 pt Amling, J urol, 1994)


Introduction

Treatment Options

  • Radical Cystectomy

  • TURBT or Partial cystectomy alone

  • Radical TUR + Systemic chemo

  • Radiation: Interstitial or External Beam

  • Multimodality therapy


Treatment Options

  • Radical Cystectomy

  • TURBT or Partial cystectomy alone

  • Radical TUR + Systemic chemo

  • Radiation: Interstitial or External Beam

  • Multimodality therapy


TURBT alone

  • The main use today of TURBT alone, in muscle invasion, is mainly in its diagnostic role.

  • It’s use in trt carries the concerns of recurrence & progression.

  • Nevertheless, several studies showed that in selected pts TUR could have therapeutic value.

How this idea came up as a treatment option?

Feneley, Sem in Uro Onco, 2000


TURBT alone

  • 10-17% of post TURBT cystectomies showed pT0.

  • TCC frequently affect elderly


TURBT alone

Technique

  • Radical TUR

    • Tumor resection to cancer-free margin, requires complete resection of all macroscopic tumor through the bladder wall to extravesical connective tissue.

Feneley, Sem in Uro Onco, 2000


TURBT alone

Concerns:

  • Feasibility to:

    • Adequately staged

    • Adequately resection of the tu

    • Field changes

Laufer, Sem in Uro Onco, 2000


TURBT alone

Limitations:

  • In 662 TURs, systematic bx were done from the base, sides & adjacent margins

    • 35% (232) showed residual tu

    • 84% (195) were invasive

      Residual noted in solid (76%) > papillary (21.5%)

This can be solved by selection criteria

Kolozsy, Br J Urol, 1991


TURBT alone

Study

  • 133 pts

    • w invasive TCC bladder

    • treated by radical TUR

    • who had (–ve) bx of the ms layer of the tumor bed.

  • F/U

    > 5 years for all subjects

    > 10 years 44.4%

Solsona; J urol, 1998


TURBT alone

  • control gr

    • 76 patients with invasive pathological stage pT2-3a, N0-3

    • treated by cystectomy.

Solsona; J urol, 1998


Comparison of results between:

gr 1 (59 pts f/u > 10 yrs) and gr 2 (74 pts f/u > 5 yrs)


Superficial bl or upper tract

Or prostatic mucosa

Or CIS requiring cystectomy

  • Progression was concentrated in the first 3 years (75.6%).

  • In 3 patients disease progressed at > 5 years (65, 71 & 92 mo)

  • None in f/u of > 10 yrs.

Comparison of results between:

gr 1 (59 pts f/u > 10 yrs) and gr 2 (74 pts f/u > 5 yrs)


35 (26.3%)

18 (30.5%)

37 (27.8%)

20 (34%)

Followup of entire series

  • In more details


TURBT alone

Followup

  • At 5 & 10 yrs of f/u

    • cause specific survival rates were 80.5 and 74.5%,

    • bl preservation rates were 82.7 and 79.6%,

  • 44.4% alive & free

  • 36% died free from dis

  • 23.7% alive & free

  • 50.8% died free from dis


No significant difference in cause specific survival, with the control group

Comparison of cause specific survival of all patients (cT2-3a, N0) and controls (pT2-3a, N0-3).


TURBT alone

Another Study

  • 217 pt

    • 79% not candidate for TUR, but for radical or partial

    • 21% (45 pt) TUR candidate.

      • F/U for median of 5.1 yrs

      • Overall survival = 82% (37/45 pt)

      • 67% (30/45 pt) w functioning Bl

        • 9 free

        • 21 required repeated superficial TUR w or w/o BCG

Herr; urol clinic, 1992


TURBT alone

Exclusion Criteria

>T2b

Wide spread CIS

Multiple TCC

>3 cm

+ve TCC at the tumor’s bed on 2nd TUR

Herr; urol clinic, 1992


TURBT alone

Exclusion Criteria

Other studies reported

less favorable outcome

But didn’t follow rigid selection criteria.

>T2b

Wide spread CIS

Multiple TCC

>3 cm

+ve TCC at the tumor’s bed on 2nd TUR

Herr; urol clinic, 1992


TURBT alone

Final Comments:

  • No randomized trials comparing it w other options like Radical or multi modality.

  • In view of the tolerability of current radiation +/- chemo, the role fro TUR alone diminished.

  • Probably useful in selected case w:

    small T2,

    + elderly pt

    + Not candidate for Radiation +/- chemo

Laufer, Sem in Uro Onco, 2000


Partial Cystectomy

  • Advantages

    • full-thickness resection

    • adequate margins.

    • LN sampling

    • Resect inaccessible tu through TUR

      • In diverticulum, dome, over ureteral orifice.

  • Drawback

    • Risk of intravesical recurrence

    • Risk of extravesical recurrence

      • decline in more contemporary series to 0%

Laufer, Sem in Uro Onco, 2000


Partial Cystectomy

Selection Criteria

  • Solitary

  • Location (usually upper ½, or 5cm)

    • Amenable to complete resection w free margins

  • Absence of CIS

  • Size

    • Should allow complete resection w/o affecting bl. function.

    • No > 50% should be removed

Dandekar, J Surg Oncol, 1995


Partial Cystectomy

Outcome

Local recurrence rate: 38-78%

Sweeny, uro clin, 1992


Partial Cystectomy

Outcome

Laufer, Sem in Uro Onco, 2000

  • In a review of series from the last 40 yrs:

  • 5 yrs survival:

    • T230- 100%

    • T3a 16- 88%

    • T3b 0 - 45%

  • Dandekar, J Surg Oncol, 1995

  • 20 TCC

    • 5 T2a, 18T2b, 9 T3

  • More to the higher

  • Overall actuarial survial = 80.1% at 5 yrs

  • Barrilero, Actas Urol Esp - 1997

  • 45 pts T2 or higher,

  • f/u = 9-258 mo

  • Partial cystectomy alone.

  • 21 cases showed bladder relapse

  • Survival even better

  • But this is a highly selected gr


Analysis of 300 cystectomies in the Univ of California LA

The results looks the same

Overall survival (Surv) of patients treated w cystectomy for bladder cancer stratified by pathological stage

Those with N0 stratified by pathological stage.

DALBAGNI, J OF UROL, 2001


Partial Cystectomy

Final Comments

  • It should be noted that

    • Rigid pt selection  good long-term result w partial cystectomy alone,

    • Only suitable for 10% of the pt

Dandekar, J Surg Oncol, 1995


No randomized trials comparing partial w Radical or multimodal bladder-preserving options.

Partial Cystectomy

Final Comments

Laufer, Sem in Uro Onco, 2000

  • No properly designed study have determine long-term result of partial.

  • It should be limited to pt w CI to Radical.


Introduction

Treatment Options

  • Radical Cystectomy

  • TURBT or Partial cystectomy alone

  • Radical TUR + Systemic chemo

  • Radiation: Interstitial or External Beam

  • Multimodality therapy


Radical TUR + Systemic Chemo

  • Rationale

    • Experience with systemic chemo indicate some improvement of the local control.

  • In 1982,

    • Socquet reported a favorable result in 25 pt using Methotrexate w folinic a. post partial cystec. for T3a.


Radical TUR + Systemic Chemo

Study

  • Collaborative N. of England gr.

  • treated 61 pts w T2/3 but used:

    • Radical TUR

    • X4 chemo (Methotrexate)

    • Repeated cysto/ TUR

    • If tu persist  conventional trt

Robert, Clinical Mgt of Bl CA, 1999


Radical TUR + Systemic Chemo

  • Of the 61 pts:

    • 17 (28%) had persistent tu

    • 15 (25%) developed recurrent invasive tu

      • at median of 18 mo

      • Treated by radical cysto or radiation

    • 15 (25%) recurrent superficial tu

  • Overall 29/61 (48%) remain free of invasive tu

Robert, Clinical Mgt of Bl CA, 1999


Radical TUR + Systemic Chemo

  • This same gr (Collaborative N. of England gr) added cisplatin to methotrexate (55 pts) and the whole population of 116 pt published recently:

  • Median f/u 11.6 yrs (4-15yrs)

    • 13 yrs for the old gr of methotrexate + folinic a

    • 8 yrs for the combination gr

Robert, Clinical Mgt of Bl CA, 1999


Radical TUR + Systemic Chemo

  • Most tu were < 5 cm

  • Only 13% were T2 (the rest were higher)

  • Random bx were not taken

    • ?CIS status is not known

    • 17 pt in the combination gr had adjacent CIS

  • Most pts in this series had G3 (78.4%)

With all these potential –ve factors, what was the outcome?

Robert, Clinical Mgt of Bl CA, 1999


Radical TUR + Systemic Chemo

  • The actuarial disease-specific survival

  • For the 1st gr

    • 2, 5, 10 yrs

    • 69%, 39%, 33%

  • For the 2nd gr

    • 82%, 70%, 61%

  • Only 28% of pts w combination trt required cystectomy or radiotherapy

The results in this selected population compare favorably w conventional trt

Robert, Clinical Mgt of Bl CA, 1999


Radical TUR + Systemic Chemo

  • Similarly good results reproduced in other centers in Europe

    • Many published in BJU from 1991-1997

    • They also used MVAC, CMV, 5FU,

  • In the MSKCC tried neoadj MVAC in 32 pt w 75% preserving their bladder in a median f/u of 19 months

Feneley, Sem in Uro Onco, 2000


Radical TUR + Systemic Chemo

In conclusion

  • The results discussed of the combination chemo + conservative surgery suggest that the approach should be tested in a randomized comparison w more conventional approaches


Introduction

Treatment Options

  • Radical Cystectomy

  • TURBT or Partial cystectomy alone

  • Radical TUR + Systemic chemo

  • Radiation: Interstitial or External Beam

  • Multimodality therapy


Radiation Therapy

  • In several European centers, the combination of external beam and interstitial radiotherapy is standard trt in a selected group w muscle-infiltrating TCC.

Wijnmaalen, Sem in Uro Onco, 2000


Radiation Therapy

  • In Rotterdam:

    • Initially, Radium needles

    • Later, cesium-containing needles.


Radiation Therapy

Interstitial radiation

  • Advantages:

    • High local dose to the tu in short time.

    • Less toxicity to the surrounding tissue.

  • Never became widely used due to:

    • Modern technique of Ex Beam RT.

    • Advancement of anesthesia & surgery time.

  • But in several European ctrs IRT

    • further developed &

    • remain the standerd for selected pts

Wijnmaalen, Sem in Uro Onco, 2000


Radiation Therapy

IRT

  • Almost exclusively in Europe.

  • Only 2 small series published in USA.

  • Criteria of IRT:

    • Solitary

    • <5cm

    • No LN or distal metz

    • Pt condition should permit surgery


Radiation Therapy

Afterload:

  • The afterload technique 1st reported in 1969.

  • Adopted in 1989 in France

  • Radio active material is introduced post op

  • Less exposure to the personnel


Steps of the combination EBRT + IRT

  • TUR or partial

  • Low EBRT (11 Gy) + high IRT (50 Gy)

  • Or high EBRT (30-40 Gy) + high IRT (30 Gy)

Wijnmaalen, Sem Uro Onc, 2000


EBRT + IRT

Results:

  • Summery of six published studies;

  • 5 yrs of:

    • Local control= 64- 88%

      • Relapse rate 11-36%

    • Distant metz 14-24%

    • Actuarial overall survival= 47-66%

    • Disease-free survival= 62%-81%,

Wijnmaalen, Sem Uro Onc, 2000


EBRT + IRT

Results

  • MR= 1.5-3%

  • Wound complication were not uncommon

    • Generally resolved by conservative mgt.

  • Necrosis at the area of the tu in 14-20%

    • Causes no complaints in most pts

    • Transient.

  • Ureteral stenosis was reported by some.

Wijnmaalen, Sem Uro Onc, 2000


EBRT + IRT

In Conclusion:

  • The approach of combining EBRT + IRT is successful in preserving the normal bladder.

  • The risk of bladder relapse appears to be higher in pt started the RT after recurrent disease.

Wijnmaalen, Sem Uro Onc, 2000


In Conclusion:

  • Conditions for good results are:

    • careful selection of patients w ms invasion,

    • excellent cooperation between

      • urologist

      • radiation oncologist

      • modern brachytherapy facilities.


Introduction

Treatment Options

  • Radical Cystectomy

  • TURBT or Partial cystectomy alone

  • Radical TUR + Systemic chemo

  • Radiation: Interstitial or External Beam

  • Multimodality therapy


Multimodality therapy

(chemotherapy in conjunction w radiation)

  • Since the 1980s, several single and multi-institutional trials were done on the combined modality organ-preserving approach.

  • Limitation of these series:

    • Not consistently use the same dose of chemo/RT

    • Not the same sequence of RT/CT

    • However, they do argue strongly for further Ix.


Multimodality therapy

Single-Institutional Trials


  • Published in 1993 & updated in 1997

  • Non random.

  • T2-4 Nx Mo

  • TUR>NACx2>RT/Cis>repeat cytology, cysto, Bx

    • If –ve continue RT/CT

    • If +ve Radical cysto

  • 57/76 (75%) had bl free of tu w median f/u of 64 mo.

  • The 5yr freedom from invasive recurrent among all pts was 79%

  • Few important points:

    • Combination TUR/RT/CT even when unsuccessful didn’t compromise overall survival

    • T2 : better outcome

    • Complete TUR > incomplete: Hydro did < w/o


86%

3 metz on each arm

  • 1988-1991, 54 pts T2-4

  • Altered CT/RT dose/fraction to increase tu kill w/o inc in SE

    • Intermittent CT 1,2,3,15,16 & 17

    • BID RT(3 Gy) 1,3,15 & 17

  • At 6 wks repeat cyst & Bx

  • If CR :either Cystectomy or RT/CT x 2 wks

  • If PR : cystectomy

No sig diff


Multimodality therapy: Single-Institutional Trials

  • RTOG gr

    • Following the same protocol

    • 34 pt T2-T4a

    • 26 visible complete TUR

    • 65% (22pts)= no tu detected on repeated cysto

    • 35% (11pts)= detected tu

      6pts cystec+5 RT

Shipley, Int J Rad Onc Bio Phys, 1999


Multimodality therapy: Single-Institutional Trials

RTOG gr

  • 11/27 ( w conserved bl) had local relapse

  • 3/11 required cystectomy for invasive

  • At 2 yrs

    • 71% alive w intact bl

    • Actuarial over all survival 87%

  • Encouraging, but require longer f/u.

Shipley, Int J Rad Onc Bio Phys, 1999


Multimodality therapy: Single-Institutional Trials

In conclusion

  • Other studies w longer f/u data support the role of bl preserving therapy.

  • Alternate regimen can provide results= standard

  • Important Q:

    • Which chemo most appropriate?

      • Taxol: signif activity as single & in combination.

      • Gemcitabine: reasonable activity & radiosensitizing.

Thurman, Sem Uro Onc, 2000


Multimodality therapy

Multi-institutional trials


Multimodality therapy Multi-institutional trials


Multimodality therapy Multi-institutional trials

  • NCI of Canada (Dr. Coppin in BC)

  • 99 pts T2- T4

  • Coppin, J clin Onco,1996

  • 91 pts T2-4

  • x2 MCV regimen>RT 40 Gy/cis>85 underwent complete urologic evaluation

  • 68 (75%) CR

  • 14 operable patients with residual tumor underwent immediate cystectomy.

  • Of 70 patients treated with consolidation cis/RT:

    • 23 invasive had salvage cystectomy /36 bladder recurrences,

    • = total of 37 of 91 patients (40%) required cystectomy.

  • The 4-year:

  • cumulative risk of invasive local failure was 43%

  • actuarial risk of distant metastasis was 22%

  • actuarial survival rate of the entire group was 62%

  • actuarial rate of survival with bladder intact was 44%

    • Tester, J clin Onco,1996


Multimodality therapy

In 10 trials of CT/RT

Side Effects

  • Acute:

    • 40-70% N/V/D, neutropenia, fatigue

  • MR 1.1% (9/807)

  • 1% required cystectomy for sever bl pain or dysfunction

  • GU symptoms: 0-15%

Therman, Sem Uro Onc, 2000


In Summery

  • Multimodality consistently confers equivalent overall survival, in selected patients, compared with survival following radical cystectomy.

  • These trials are very encouraging and allow organ preservation to be considered an appropriate therapeutic option for selected patients with muscle-invasive bladder cancer.


General Summery

  • The role of neoadjuvant chemo is not clear.

    • Requires further study

  • It is not clear which drug or combination of drugs is the most efficacious?

  • The results hypofractionation of RT/CT are provocative. ? long f/u

  • Molecular & cellular biomarkers may in the future improve the Dx & the delivery of individualized therapies.


General Summery

  • Bladder-preserving strategies have been shown to be feasible w encourging results in selected pts w muscle invasive, organ-confined bladder CA.

  • With careful f/u cystectomy is not delayed in pt w truly local failures.


General Summery

  • With the diversity of opinions in the management, options need to be discussed with patients.


ad
  • Login