EURURO Vol. 72 No. 3

Letter to the Editor

Reply to Saeid Safiri and Erfan Ayubi’s

Letter to the Editor re: Nicholas J. Giacalone,

William U. Shipley, Rebecca H. Clayman, et al.

Long-term Outcomes After Bladder-preserving

Tri-modality Therapy for Patients with Muscle-invasive

Bladder Cancer: An Updated Analysis of the

Massachusetts General Hospital Experience.

Eur Urol 2017;71:952–

[1_TD$DIFF]

60. Methodological Issues to

Avoid Misinterpretation

We thank Safiri and Ayubi for their insightful comments on

our paper

[1] .

It is important to note that the purpose of our

study was to report on our institution’s long-term outcomes

for muscle-invasive bladder cancer (MIBC) treated with

[2_TD$DIFF]

tri-

modality therapy (TMT); this included use of a Cox

regression model to identify clinical and treatment factors

that were associated with overall survival (OS) and disease-

specific survival (DSS) in our patient population. However,

we did not, as was suggested by Safiri and Ayubi, create or

report on a prediction model, as this was not the goal of our

study. Similarly, we did not report on model performance

using any apparent validation measures. Nevertheless, here

we provide the apparent validation and internal validation

(using optimism-corrected estimates) for both OS and DSS

to address the authors’ concerns regarding our methodolo-

gy. For OS, Harrell’s concordance index is

= 0.663

(apparent validation). The optimism, based on 1000 boot-

strap samples

[2]

, is 0.005. Therefore, the optimism-

corrected

is 0.663 0.005 = 0.658 (internal validation).

For DSS, Harrell’s concordance index is

= 0.658. The

optimism,

based on 1000 bootstrap samples,

0.0007. Therefore, the optimism-corrected

is practically

identical to the optimism-uncorrected (sample)

index.

The very low values for optimism indicate that bias due to

model overfitting was negligible. Regarding our stepwise

selection Cox regressionmodel, we used backward stepwise

selection with a 0.2 significance level for removal from the

model. We also used the Akaike information criterion to

monitor parsimony and the relative quality of competing

multivariable models.

In addition, we are pleased to see the recent encouraging

results from Kulkarni et al

[3] ,

who used a propensity score

matched analysis to compare outcomes fromMIBC patients

treated with radical cystectomy (RC) versus TMT between

2008 and 2013. Their findings revealed no significant

difference in 5-yr DSS among patients treated with RC or

TMT (73.2% vs 76.6%;

= 0.49). Furthermore, the updated

treatment guidelines for nonmetastatic MIBC published by

the consortium of the American Urological Association,

American Society of Clinical Oncology, American Society for

Radiation Oncology, and Society for Urologic Oncology have

included TMT as a recommended treatment approach for

these patients, with the same strength of recommendation

and evidence level as for RC (strong recommendation;

evidence level, grade B)

[6] .

Taken together with our own

data and those of others

[4,5]

, the findings by Kulkarni et al

and the updated treatment guidelines continue to support a

greater role for TMT in the management of MIBC, and

underscore the need for multidisciplinary discussions when

reviewing treatment options with these patients.

Conflicts of interest:

The authors have nothing to disclose.

References

[1] Giacalone NJ, Shipley WU, Clayman RH, et al. Long-term outcomes

after bladder-preserving tri-modality therapy for patients with

muscle-invasive bladder cancer: an updated analysis of the Mas-

sachusetts General Hospital experience. Eur Urol 2017;71:952–60.

http://dx.doi.org/10.1016/j.eururo.2016.12.020

[2]

Steyerberg E. Clinical prediction models: a practical approach to development, validation and updating. Berlin: Springer; 2009.

[3] Kulkarni GS, Hermanns T, Wei Y, et al. Propensity score analysis of

radical cystectomy versus bladder-sparing trimodal therapy in the

setting of a multidisciplinary bladder cancer clinic. J Clin Oncol

2017;35:2299–305.

http://dx.doi.org/10.1200/JCO.2016.69.2327 .

[4] Mak RH, Hunt D, Shipley WU, et al. Long-term outcomes in patients

with muscle-invasive bladder cancer after selective bladder-pre-

serving combined-modality therapy: a pooled analysis of Radiation

Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906,

and 0233. J Clin Oncol 2014;32:3801–9.

http://dx.doi.org/10.1200/ JCO.2014.57.5548 .

[5]

Krause FS, Walter B, Ott OJ, et al. 15-year survival rates after transurethral resection and radiochemotherapy or radiation in bladder cancer treatment. Anticancer Res 2011;31:985–90.

[6] American Urological Association. Treatment of non-metastatic

muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline.

https://www.auanet.org/documents/education/clinical-guidance/ Muscle-Invasive-Bladder-Cancer.pdf . E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) e 6 4 – e 6 5

available at

www.scienced irect.com

journal homepage:

www.europeanurology.com

DOIs of original articles:

http://dx.doi.org/10.1016/j.eururo.2016.12.020 , http://dx.doi.org/10.1016/j.eururo.2017.06.008

http://dx.doi.org/10.1016/j.eururo.2017.06.007

0302-2838/