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Platinum Priority – Editorial

Referring to the article published on pp. 776–787 of this issue

Prostate Cancer and Immune Monitoring: Are We Heading

Towards Better Selection of Patients and Treatment Strategies?


Martijn Lolkema, Reno Debets, Ronald de Wit



Medical Oncology Department, ErasmusMC Cancer Institute, Rotterdam, The Netherlands

In less than two decades, the management of metastatic

prostate cancer has evolved from castration only to a

complex therapeutic field. Thus far, prostate cancer

nomenclature has reflected the point in time relative to

treatment, such as castration-resistant disease and post-

docetaxel disease. However, potential different subtypes

with therapeutic consequences have not developed beyond

Gleason’s classification of the primary tumor. The first real

attempt to improve classification comes from work on DNA

repair deficiencies, as up to 20% of prostate cancers harbor

defects in DNA repair pathways, so there is potential to

characterize a subgroup sensitive to DNA repair pathway



. However, the question arises as to whether

this is the best we can do.

Molecular stratification of tumors has mostly developed

for tumor types that showed a clear need for identifying

(non-)responders to therapy. For prostate cancer, however,

a mere non-response to initial castration therapy is

uncommon. Of note, the majority of the clinical and

preclinical work on metastatic prostate cancer points

towards a crucial role of the androgen receptor (AR) in

driving this disease. These studies have provided the basis

for developing novel antihormonal treatments such as

enzalutamide and abiraterone that target residual AR

activity after castration, and mechanisms of resistance to

these compounds have been associated with reactivation of

the AR pathway

[2] .

In addition, chemotherapy in prostate

cancer may, at least in part, represent a different way of

manipulating AR signaling


. Thus, our paradigm has

remained that prostate cancer is a disease that mainly

depends on hormones.

In this issue of

European Urology

, Bovinder Ylitalo et al


present their work on a 40 samples from a unique tissue

collection of 65 bone metastasis samples from surgical

resections. This tissue collection is unique; well-preserved

samples from bone metastases with sufficient amounts of

tissue for multiple validations are hard to obtain. Bovinder

Ylitalo and colleagues describe a robust analysis of gene

expression and validation by polymerase chain reaction and

in situ staining that point towards a subset of non–AR-

driven tumors. The non–AR-driven subgroup was charac-

terized on the one hand by low activities for cholesterol



-oxidation, and polyamine synthesis, and on

the other hand by high immunogenicity.

Although Bovinder Ylitalo and colleagues are to be

congratulated on their research findings, their work does

show some inherent weaknesses. The sample size of the

study (40 samples to construct a classifier) is limited.

Unsupervised clustering among such small samples is prone

to deliver false-positive signals. Moreover, the source of the

tissue may give rise to bias; patients who underwent

resection are likely to represent a selected subset of

patients, since palliative radiotherapy is a more common

approach for local treatment in most instances. Despite

these weaknesses, the study does provide the first evidence

connecting lower levels of immune cells and antigen

presentation with high AR signaling activity. These data

warrant and are highly likely to spark further studies to

unravel the mechanisms behind the suppression of antigen

presentation and low numbers of intratumoral monocytes

and T lymphocytes. Changes in tumor biology and

microenvironment that potentially determine the number

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

available at


journal homepage:

DOI of original article:


* Corresponding author. Medical Oncology Department, ErasmusMC Cancer Institute, P.O. Box


5201, 3008




Rotterdam, The Netherlands.

Tel. +31 10 7041505.

E-mail address:

(R. de Wit).



2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.