EURURO Vol. 72 No. 4

Platinum Priority – Editorial

Referring to the article published on pp. 544–554 of this issue

Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer:

Are Things Now Getting Personal?

Matthew D. Galsky

a , * ,

John P. Sfakianos

b ,

Bart S. Ferket

Division of Hematology/Oncology, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;

Departments of Medicine and Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA;

Department of Population Health Science and Policy,

Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Level 1 evidence supports the use of neoadjuvant

chemotherapy (NAC) for muscle-invasive bladder cancer

(MIBC), although observational studies have revealed that

such treatment is vastly underutilized; a reason com-

monly cited is the inability to identify which patients

could derive most benefit from NAC. Recent studies by

several groups have demonstrated the promise of

biomarkers of ‘‘response’’ to NAC based on somatic

mutation or gene expression

[1–3] .

These studies are

highly promising but have mainly consisted of small

patient cohorts and have focused on an intermediate

clinical endpoint (ie, pathologic complete response), so

much additional work is required before translation into

clinical practice.

In this issue of

European Urology

, Seiler et al

[4]

take an

initial, but critical, step forward in bringing biomarker-

based decision-making to patients with MIBC. The authors

assembled several retrospective cohorts to discover, and

validate, a single-sample classifier that assigns MIBC to one

of four subtypes on the basis of a consensus of previously

published classifications schemes. Comparison of subtype-

stratified survival estimates across cohorts of patients

treated with and without NAC revealed that patients with

basal tumors experienced poor outcomes with cystectomy

alone and seemingly better outcomes with NAC followed by

cystectomy. This shift in survival on cross-cohort compar-

isons was not observed for the other three MIBC subtypes

(luminal, luminal infiltrated, and claudin-low), leading the

authors to conclude that NAC may only benefit patients

with basal MIBC.

This study by Seiler et al represents an advance on

several levels. This group has developed a molecular

classifier that:

(1) Harmonizes MIBC subtypes developed by independent

groups;

(2) Can be utilized to subtype a single patient’s tumor; and

(3) Can be performed on formalin-fixed paraffin tumor

tissue in a Clinical Laboratory Improvement Amend-

ments–certified environment.

Overcoming these obstacles, which represent some key

contributors to the ‘‘biomarker valley of death’’, is a major

accomplishment on the path towards clinical qualification.

However, where can we go from here?

Analytical validation aside, predictive biomarkers must

demonstrate clinical validity and ultimately clinical utility.

Clinical validity implies that the biomarker correlates with a

clinical outcome, while clinical utility implies that use of the

biomarker results in patient benefit by informing treatment

decisions. Similar to the principles applied to studies

exploring novel therapies, given the potential harms

associated with biomarker-based decision-making, bio-

marker studies should be interpreted in the context of their

level of evidence. Although several guidelines have been

established, the levels of evidence recommended by the

American Society of Clinical Oncology Tumor Markers

Guidelines Committee, and expanded on by Simon and

colleagues for ‘‘use of archived specimens in evaluation of

prognostic and predictive biomarkers’’, are particularly

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 5 5 5 – 5 5 6

ava ilable at

www.sciencedirect.com

journal homepage:

www.eu ropeanurology.com

DOI of original article:

http://dx.doi.org/10.1016/j.eururo.2017.03.030

* Corresponding author. Division of Hematology and Medical Oncology, Department of Medicine, The Tisch Cancer Institute, Icahn School of Medicine

at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Tel. +1 212 8248583; Fax: +1 646 5379639.

E-mail address:

matthew.galsky@mssm.edu

(M.D. Galsky).

http://dx.doi.org/10.1016/j.eururo.2017.04.012

0302-2838/