EURURO Vol. 72 No. 4

Platinum Priority – Editorial and Reply from Authors

Referring to the article published on pp. 483–487 of this issue

Trimodal Therapy is Inferior to Radical Cystectomy for

Muscle-invasive Bladder Cancer using Population-level

Data: Is There Evidence in the (Lack of) Details?

Girish S. Kulkarni

a , b , * ,

Zachary Klaassen

Division of Urology, Departments of Surgery and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of

Toronto, Toronto, ON, Canada;

Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada

Radical cystectomy (RC) is considered the gold-standard

treatment for localized, muscle invasive bladder cancer

(MIBC) according to the majority of oncologic governing

bodies. RC, however, carries with it significant morbidity (30-

d postoperative: 31–51%)

[1]

and a realistic risk of mortality

in the elderly (30-d postoperative: 7–18%)

[2,3] .

These

factors likely underlie its relative underutilization as curative

local therapy, as population-based data suggest that only 21%

of patients 66 yr of age with localized MIBC undergo RC

[4] .

Clearly, alternative therapies that are safe, tolerable and

offer the opportunity for cure are desperately needed.

Bladder preservation with trimodal therapy (TMT; com-

plete transurethral resection of the bladder tumor [TURBT]

followed by concomitant radiotherapy and chemotherapy)

may represent one such treatment. TMT is typically reserved

for two unique patient subsets: those that are medically unfit

for RC or those who meet strict criteria for curative intent

[5] .

Ideal candidates for TMT have been described as those

with small, solitary muscle-invasive tumors, no significant

carcinoma-in-situ (CIS), no hydronephrosis, and who have

undergone complete TURBT without evidence of visible

tumor remaining

[6]

. TMT can thus be seen as a secondary

treatment for those unfit or unwilling to undergo RC or as

first line, definitive therapy for select patients with MIBC.

After thorough consultation with the multidisciplinary

bladder cancer team, TMT may be an option for those

patients seeking bladder preservation with cure.

In this issue of

European Urology

, Seisen et al

[7]

utilized

the National Cancer Data Base (NCDB) to assess overall

survival (OS) among 1257 (9.8%) patients undergoing TMT

and 11 586 (90.2%) patients receiving RC for cT2-4N0M0

bladder cancer. Median OS was similar for patients receiving

TMT (40 mo, 95% confidence interval [CI]: 34–46) and RC

(43mo, 95% CI: 41–45,

= 0.3); however, TMTwas associated

with worse OS after 25 mo of follow-up (hazard ratio [HR]:

1.37, 95% CI: 1.16–1.59) when a time-varying covariate was

introduced into the model. There was no significant

difference between TMT and RC when considering interac-

tion terms for sex, Charlson Comorbidity Index, or cT-stage;

however, the

adverse

treatment effect of TMT decreased

significantly with age (HR: 0.99, 95% CI: 0.98–0.99),

suggesting that TMT may be best utilized in elderly patients.

The authors should be commended for their rigorous and

advanced methodology applied to this population-based

dataset. The advantages of using population-level data for

assessing clinical questions such as TMT versus RC for

treatment of MIBC include a large sample sizewith long-term

follow-up. Nevertheless, one must be careful when inter-

preting these results particularly when considering the

indications for TMT as well as the limitations of the database

used. First, the strict TMT criteriadefined above are difficult to

determine from population-level data, specifically TURBT

quality (ensuring complete resection), tumor size and

multiplicity, extent of CIS (if any), and presence of hydrone-

phrosis. Complete visual resection of the bladder tumor is a

strong predictor of oncologic control and TMT success, with a

20% increase in response and long-termbladder preservation

amongst patients who have complete TURBT

[8]

. Invariably, if

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 4 8 8 – 4 9 1

available at

www.scienced irect.com

journal homepage:

www.europeanurology.com

DOI of original article:

http://dx.doi.org/10.1016/j.eururo.2017.03.038

* Corresponding author. Division of Urology, Adjunct Scientist, Institute for Clinical Evaluative Sciences, University Health Network, Princess Margaret

Hospital, 610 University Avenue, Suite 3-130, Toronto, ON M5G 2M9, Canada. Tel. +1-416-946-2246; Fax: +1-416-946-2180.

E-mail address:

girish1975@gmail.com

(G.S. Kulkarni).

0302-2838/