Is there still a role of

cystectomy?
Nicholas James
@Prof_Nick_James

Yes!

But..
Should we reappraise if it should be the
central plank of a treatment strategy?

Overview
Evidence base for bladder preservation
as alternative to surgery
Chemoradiotherapy compared to
radiotherapy alone

Age standardised 5 year survival rates in UK

Prepared by Cancer Research UK - http://info.cancerresearchuk.org/cancerstats/

Age-standardised 5-year survival for

bladder cancer 19992007
N Europe

Central Europe

Eastern Europe

Rafael Marcos-Gragera, et al Urinary tract cancer survival in Europe 19992007: Results of the
population-based study EUROCARE-5 European Journal of Cancer, Volume 51, Issue 15, 2015, 2217
2230 http://dx.doi.org/10.1016/j.ejca.2015.07.028

Ireland and UK

Southern Europe

Europe

Background
Bladder cancer outcomes have not
significantly improved for 30 years
Zehnder P, Studer UE, Skinner EC, Thalmann GN, Miranda G, Roth B, Cai J,
Birkhauser FD, Mitra AP, Burkhard FC, Dorin RP, Daneshmand S, Skinner DG,
Gill IS. Unaltered oncological outcomes of radical cystectomy with extended
lymphadenectomy over three decades. BJU Int 2013;112:E51-8

Presented by: Nick James

Background
Bladder cancer outcomes have not
significantly improved for 30 years
Zehnder P, Studer UE, Skinner EC, Thalmann GN, Miranda G, Roth B, Cai J,
Birkhauser FD, Mitra AP, Burkhard FC, Dorin RP, Daneshmand S, Skinner
DG, Gill IS. Unaltered oncological outcomes of radical cystectomy with
extended lymphadenectomy over three decades. BJU Int 2013;112:E51-8

Presented by: Nick James

Is survival better after surgery?

Survival from UK Registry data

453 UK pts, 19931996
Ratio
RT:cystectomy 3:1
10 year survival RT
22% Surgery 24%

Munro NP, Sundaram SK, Weston PM, et al. A 10-year retrospective review of a nonrandomized cohort of 458 patients
undergoing radical radiotherapy or cystectomy in Yorkshire, UK. Int J Radiat Oncol Biol Phys 2010;77:119-24.

Canadian Registry Data

Bladder Cancer
Variations in the use of total cystectomy and in the
use of pelvic RT among the regions of Ontario
were not associated with variations in survival.
Survival was correlated with tumour related
parameters

Hayter CR, Paszat LF, Groome PA, et al: The management and outcome of bladder carcinoma
in Ontario, 1982-1994. Cancer 89: 142-151, 2000

Radical cystectomy versus organ-sparing

trimodality treatment in muscle-invasive
bladder cancer: A systematic review of clinical
trials
G. Arcangeli, L. Strigari, S. Arcangeli

Critical Reviews in Oncology / Hematology

Volume 95, Issue 3, Pages 387-396 (September 2015)
DOI: 10.1016/j.critrevonc.2015.04.006

Copyright 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 1

Critical Reviews in Oncology / Hematology 2015 95, 387-396DOI: (10.1016/j.critrevonc.2015.04.006)

Copyright 2015 Elsevier Ireland Ltd Terms and Conditions

5-year OS rates of patients undergoing RC or TMT

Critical Reviews in Oncology / Hematology 2015 95, 387-396DOI: (10.1016/j.critrevonc.2015.04.006)

Copyright 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 3
5-year OS rates of patients undergoing RC or TMT

Critical Reviews in Oncology / Hematology 2015 95, 387-396DOI: (10.1016/j.critrevonc.2015.04.006)

Copyright 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 4
5-year OS rates of patients undergoing RC or TMT

Critical Reviews in Oncology / Hematology 2015 95, 387-396DOI: (10.1016/j.critrevonc.2015.04.006)

Copyright 2015 Elsevier Ireland Ltd Terms and Conditions

What can we learn from other

cancers?

Anal cancer
Primary therapy was surgery up until mid-1980s
Various chemo-RT regimens showed high
activity with range of agents including 5FU,
MMC, cisplatinum during 1970s
surgery as the primary therapeutic modality
has been abandoned.
Anal cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment
and follow-up Ann Oncol (2014) 25 (suppl 3):iii10-iii20.doi: 10.1093/annonc/mdu159

Can we salvage local failures?

Primary vs Salvage Cystectomy

Addla et al. The Journal of Urology Vol. 181, Issue 4, Supplement, Page 633

Are complication rates higher

with salvage cystectomy?
426 primary and 420 salvage cystectomies
Single institution
1970-2005

Differential Complication Rates Following Radical Cystectomy in the Irradiated and Nonirradiated Pelvis
Vijay A.C. Ramani, Satish B. Maddineni, Ben R. Grey, Noel W. Clarke. Eur Urol 57 (2010) 10581063

Are complication rates higher

with salvage cystectomy?

Differential Complication Rates Following Radical Cystectomy in the Irradiated and Nonirradiated Pelvis
Vijay A.C. Ramani, Satish B. Maddineni, Ben R. Grey, Noel W. Clarke. Eur Urol 57 (2010) 10581063

Are complication rates higher

with salvage cystectomy?
This large series from a high-volume
centre demonstrates no difference in
perioperative mortality in primary or
postradiation salvage radical cystectomy.
Similarly, there was no significant
difference in the incidence of most of the
surgical or medical complications..
Differential Complication Rates Following Radical Cystectomy in the Irradiated and Nonirradiated Pelvis
Vijay A.C. Ramani, Satish B. Maddineni, Ben R. Grey, Noel W. Clarke. Eur Urol 57 (2010) 10581063

Age at diagnosis
Median age in

1600

BC2001 and BCON

1400

Median age in

1200

USC series

1000

M a le c a s e s
F e m a le c a s e s

Median age in

800

BA06 & SWOG 8710

600

400

200

0
0 -4

5 -9

1014

1519

2024

2529

3034

3539

4044

4549

5054

5559

6064

6569

7074

7579

8084

85+

Choice of treatment
Surgery and radiotherapy data relate to
different segments of the population
Hence age/fitness is important factor in
treatment decisions

Chemoradiation vs radiotherapy
alone

12

24

36 48
Months

60

72

1.00

12

24

36 48
Months

60

72

0.75

Residual mass post resection

0.50

0.50

0.25

0.25
<30mm
>=30mm
Unknown

Logrank test p= 0.04

Biopsy/Not resected
Complete resection
Incomplete resection

12

24

36 48
Months

60

72

0.00

Logrank test p=0.001

0.00

T2
T3-4

0.00

0.25

Logrank test p= 0.11

Extent of tumour resection

0.75

1.00
0.50

0.50
0.25
0.00

Size of tumour

0.75

0.75

1.00

Stage

1.00

Presence of residual mass, extent of

resection and tumour size are related

Logrank test p=0.005

No
Yes
0

12

The presence of residual mass was highly correlated with

extent of resection
96% complete resections without residual mass
66% incomplete resections with residual mass

24

36 48
Months

60

72

TURBT and residual mass

Residual mass = high stage
High stage = poor prognosis
Therefore does not follow that RT
only for patients with no mass post
TURBT as these patients will do
badly with surgery

Effect of Multivariate factors on ILRC

.8

71.4%

1
RT+CT

No Res
mass

RT

3-yr ILRC:
90.1%
82.9%

RT+CT
No Res mass

RT

.8

3-yr ILRC:
83.0%

Neoadjuvant CT

Proportion of invasive loco-regional control

Proportion of invasive loco-regional control

No neoadjuvant CT

72.5%
RT+CT

Neoadjuvant56.2%
chemotherapy and synchronous
56.0%
RT
chemotherapy RT+CT
do different things
35.3%

Residual
mass

.4

.4

.6

.6

Residual
mass

.2

.2

RT

12

24

36

48

60

Months since randomisation

72

12

24

36

48

60

Months since randomisation

36

72

Overall Survival

WHO 1-2, Age 70

Overall Survival

Overall Survival

0 .2 .4 .6 .8 1

0 .2 .4 .6 .8 1

WHO 0, Age 70

12

24

36

48

60

Months since randomisation

72

24

36

48

60

72

WHO 1-2, Age 80

Overall Survival

Overall Survival

0 .2 .4 .6 .8 1

0 .2 .4 .6 .8 1

WHO 0, Age 80

12

Months since randomisation

12

24

36

48

60

Months since randomisation

72

12

24

36

48

60

Months since randomisation

RT, No Res Mass

RT, Res Mass

RT+CT, No Res Mass

RT+CT, Res Mass

37

72

Patterns of recurrence after chemoRT

Conclusions
No convincing evidence surgery superior to
primary bladder preservation with salvage
surgery
Synchronous chemo-radiation is safe and
improves pelvic control and is complementary
to neoadjuvant treatment