Download Pacientes oligometastásicos: ¿hay un tratamiento diferenciado?

Pacientesoligometastásicos:¿hay
untratamientodiferenciado?
Dr.MiguelAngel Climent
FundaciónInstitutoValencianodeOncología
Esquemaquevamosaseguir…
• Definicion delasituación
• Esunaenfermedaddiseminadadelaquevemosel
principioo…
• Esunasituaciónconcaracterísticasclinicobiológicas
propias
• Numeroylocalización(abarcablesportto.único)
• Nuevaspruebasdeimagen:PET
• TratamientodelaenfermedadlocalenM1
• Linfadenectomía (cirugía)derescate
• RTenoligometastasico
sites could be treated using local therapy.
Oligometastasis yoligorrecurrencia
SYSTEMIC THERAPY AND LOCAL THERAPY
108
Oligometastases and oligo-recurrence
Improvement of systemic chemotherapy including
molecular-targeted therapy has allowed micrometastases
thera
sion
inclu
be er
state
(rang
powe
eradic
Table 1. Oligometastases and oligo-recurrence
Oligometastases
Oligo-recurrence
Reference
Hellman and
Weichselbaum (1)
Niibe et al.
(2,3,4)
Primary lesion
Uncontrolled/controlled
Controlled
No. of distant/metastases/
recurrences
One to several
One to several
(one is better)
to be almost completely absent clinically. Theoretically,
if several gross metastatic or recurrent sites could be eradiated by local therapy, these patients could be cured
with concomitant systemic chemotherapy. Punglia et al.
(5) reported that if systemic therapy improved, the role of
local therapy would improve and proposed a figure for
this Figure
correlation.
figure of Schema
the correlation
2. This is Here,
a schemaa ofnew
oligo-recurrence.
1 shows one distant
metastasis/recurrence
with
a
controlled
primary
lesion.
Schema
2 shows two
between
local
therapy
and
systemic
therapy
is
proposed
Figure 1. This is a schema of oligometastases. Schema 1 shows one distant
distant metastases/recurrences with a controlled primary lesion. The biggest
(Fig. 3), showing that the role of local therapy is initially
metastasis/recurrence with a primary lesion. Schema 2 shows two distant
difference between oligometastases and oligo-recurrences lies in the unconincreasingly
important
as lesion.
systemic
therapy requires
improves,
metastases/recurrences with a primary lesion.
trolled or controlled
primary
Oligo-recurrence
a controlled
stases and oligo-recurrence
depending
on the sigmoid curve. The current status of
primary lesion.
cancer therapy lies in the range between 0 and
between oligometastasis and oligo-recurrence are listed in
A. However, in the future, extreme improvements in sysTable 1. Oligometastases
oligo-recurrence
Table 1. In the state of oligo-recurrence,
recurrent orand
metatemic therapy will decrease the importance of local
static sites with a controlled primary lesion were treated withOligometastases
Oligo-recurrence
therapy, because
cancers will be diminished by systemic
local therapy, meaning that all gross recurrent or metastatic
Reference
Hellman and
Niibe
et al.
therapy
alone
such
as intravenous anti-cancer drug infusites could be treated using local therapy.
Weichselbaum (1)
(2,3,4)
sion or oral Controlled
anti-cancer drugs. All cancerous lesions
Primary lesion
Uncontrolled/controlled
including
gross
tumors and microinvasive tumors could
No. of distant/metastases/
One to several
One to several
be eradicated (one
withis better)
systemic therapy alone. This desirable
SYSTEMIC THERAPY ANDrecurrences
LOCAL THERAPY
state is shown as B in Fig. 3. In the present status
Figure
Until
improv
temic t
therapy
¿existecomoentidadoesunpuntodecorte?
¿existe como entidad o es un punto de corte?
Comportamiento biológico del CPRC
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ENZ,Rd
EXITUS
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16-19ms
30-35ms
20-44ms
MedianasSupervivencia
Comportamiento
del CPRC
¿existe
como entidad biológico
o es un punto
de corte?
Comportamiento biológico del CPRC
Tto
oligometa
Tto.
Local
DOCE
CBZ,AB,
ENZ,Rd
EXITUS
M1
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w.sciencedirect.com
‘‘Gotta Catch ’em All’’, or
e: www.europeanurology.com
Do We? Pokemet Approach to
Metastatic Prostate Cancer
Declan G. Murphy a,b,c,*, Christopher J. Sweeney d, Bertrand Tombal e
a
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia;
b
Australian Prostate Cancer Research Centre, Epworth Healthcare,
c
Richmond, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia;
d
Dana-Farber Cancer Institute,
e
Harvard Medical School, Boston, MA, USA; Institut de Recherche Clinique, Cliniques Universitaires Saint-Luc, Brussels, Belgium
‘‘Gotta catch ’em all’’ is the catch-cry of location-based
augmented reality game Pokemon Go, which caused a
worldwide sensation when it was launched in July
2016. Within 1 wk, it had become the most downloaded
app in the history of Apple’s App Store; within 2 mo it had
reached 500 million downloads; within 5 mo its users had
taken over 8.7 billion steps in their quest to catch Pokemon;
and despite a drop-off in users since launch, more than
20 million people still spend hours each day trying to catch
Pokemon using their smartphones. ‘‘Pokemania’’ does seem
an appropriate term to describe the phenomenon whereby
users chase around various locations trying d
to trap
a,b,c,
e
Pokemon in a fruitless effort to ‘‘catch ’em all’’.
In the world of metastatic prostate cancer, there is
ery, Peter
MacCallum
Cancer
Centre,inMelbourne,
Australia; b Australian Prostate Cancer Research Centre, Epworth Healthcare,
considerable
interest
at present
aggressive therapeutic
approaches
to oligometastatic
cancer.University
The term of Melbourne, Melbourne, Australia; d Dana-Farber Cancer Institute,
e Sir Peter
MacCallum
Department prostate
of Oncology,
metastasis-directed
therapy (MDT) has been used to describe
Boston, MA,
USA; e Institut de Recherche Clinique, Cliniques Universitaires Saint-Luc, Brussels, Belgium
surgical resection of, or stereotactic radiation therapy to,
low-volume oligometastatic lesions in selected prostate
cancer patients [1]. On the basis of experience in other
ll’’ is the
catch-cry
of location-based
tumour
types, it has
been suggested that ablative
approaches
to
oligometastatic
(typically
game Pokemon Go, whichcancer
caused
a defined as
up to 3 synchronous metastases, bone and/or lymph nodes)
on when
it orwas
in July
may defer
enhancelaunched
the need for systemic
therapy in some
with perhaps
some patients
never requiring further
it hadpatients,
become
the most
downloaded
treatment [2]. Androgen deprivation therapy (ADT) alone
on
ch ’em All’’, or Do We? Pokemet Approach to
Prostate Cancer
hy
*, Christopher J. Sweeney , Bertrand Tombal
py (SABR) with ongoing biochemical and clinical progression. Images for a 67-yreason grade group 2 prostate cancer with negative pathological margins. (A)
Declan G. Murphy a,b,c,*, Christopher J. Sweeney d, Bertrand Tombal e
¿quéesprimero…elhuevoolagallina?
a
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia;
c
b
Australian Prostate Cancer Research Centre, Epworth Healthcare,
Richmond, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia;
d
Dana-Farber Cancer Institute,
e
Harvard Medical School, Boston, MA, USA; Institut de Recherche Clinique, Cliniques Universitaires Saint-Luc, Brussels, Belgium
‘‘Gotta catch ’em all’’ is the catch-cry of location-based
augmented reality game Pokemon Go, which caused a
worldwide sensation when it was launched in July
2016. Within 1 wk, it had become the most downloaded
app in the history of Apple’s App Store; within 2 mo it had
reached 500 million downloads; within 5 mo its users had
taken over 8.7 billion steps in their quest to catch Pokemon;
and despite a drop-off in users since launch, more than
20 million people still spend hours each day trying to catch
Pokemon using their smartphones. ‘‘Pokemania’’ does seem
an appropriate term to describe the phenomenon whereby
users chase around various locations trying to trap
Pokemon in a fruitless effort to ‘‘catch ’em all’’.
In the world of metastatic prostate cancer, there is
considerable interest at present in aggressive therapeutic
approaches to oligometastatic prostate cancer. The term
metastasis-directed therapy (MDT) has been used to describe
surgical resection of, or stereotactic radiation therapy to,
low-volume oligometastatic lesions in selected prostate
cancer patients [1]. On the basis of experience in other
tumour types, it has been suggested that ablative
approaches to oligometastatic cancer (typically defined as
up to 3 synchronous metastases, bone and/or lymph nodes)
may defer or enhance the need for systemic therapy in some
patients, with perhaps some patients never requiring further
treatment [2]. Androgen deprivation therapy (ADT) alone
has limited efficacy, in contrast to ADT combined with
radiation in high-risk localized disease. In parallel, there
is much interest in aggressive approaches to the primary
cancer in men presenting with metastatic cancer, with
a number of studies ongoing in what is an experimental
Fig. 1 – The growth in publications on oligometastatic prostate cancer is
paralleled by the growth in publications on prostate-specific membrane
antigen (PSMA) positron-emission tomography (PET) imaging of
prostate cancer.
•  PaCents!data!from!8,820!men!with!mCRPC)enrolled)onto)9)phase)III)trials.)
•  Site!of!metastases:!!lymph)node)only,!bone)with)or)without)LN,!any!lung!metastases!(but!
no!liver),!and!any!liver!metastases.!
•  Specific!sites!of!metastases!in!men!with!mCRPC!are!associated!with!differenCal!OS:!LN>Bone>lung>liver))
•  These!data!may!help!in!treatment)decisions,!!design)of)clinical)trials,!and!understanding!the!variaIon)
in)biology)of)different)sites)of)metastases)in!men!with!mCRPC.!
Eur)Urol.)
2016)Mar)19)
Post hoc.
Overall Survival according to disease extension
(<4)vs)≥4)bone)mets.))
Podemossóloestarescogiendolas
mejores…
Abstract #5018
#5018 Ext vs. Lim PLND
¿Cómoeselfenómenodelasmetastasis?
I.
Halsted 1907: Ca. de mama siempre se disemina vía
linfática locorregional
la enfermedad se puede
curar si se dx en un estadío precoz.
II.
Hellman 1994: Ca. de mama siempre metastatiza
aparecen tan precozmente, que las terapias locales
son menos importantes que el microambiente
tumoral o terapias sistémicas.
I.
Fisher, Hellman 2005 “Spectrum hypothesis”:
rango entre enf. local y la enf. diseminada en el
momento del diagnóstico.
¿Cómoeselfenómenodelasmetastasis?
Las metástasis surgen de una expansión clonal, los
clones con ventajas selectivas dan lugar a metástasis
si estos clones son destruidos (p.e. con SBRT )
teóricamente podríamos reducir el potencial
metastásico.
and polymetastatic
groups
in the an
two-tailed Background:
Fisher Exact Cancer
Test). These
that
stagingdata
and demonstrate
treatment presumes
abetween
divisionthe
intooligometastatic
localized or metastatic
disease. We
proposed
intermediate
state defined
by #5from
cumulative
termeddataset
oligometastases.
In tumor
contrast
to widespread
metastatic tumor
and the primary
set independently
detected patterns
of microRNA
expression
metastaticmetastasis(es),
may benefit from
metastasis-directed
local
treatments.
many29patients
using
a two-tailed Student
t-test
(P,0.05). However,
We prioritized
and
samples arepolymetastases,
dominated byoligometastatic
oligometastaticpatients
or polymetastatic
initially
present
with S1).
oligometastases
progress to polymetastases.
Predictors
of progression
could improve
patient
17 microRNAs that
characterized
oligometastatic
or polymetaprogression who
of disease
(Fig.
1, Table
In contrast, unsuperselection
for metastasis-directed
static progression
in the two datasets, respectively (Table 1,
vised hierarchical
clustering
using microRNA therapy.
expression of tissue
1,5.
Yves A. Lussier1,2,3,4*,exclusively
H. Rosie obtained
Xing1,2,5,6.
, Joseph K. Salama8., Nikolai N. Khodarev
, Yong Huang1,3.,
Fig. 1, Figure S1). We designated these sets as 29 M-miRs
from primary tumors of patients failed to
7.
3.
5.
5 from oligometastatic patients treated with
Methods:
Here, we
identified
patterns D.
of microRNA
expression
of tumor
samples
A. Khan
Yang
, Michael
Hasselle
E. prioritized
Darga
, from
Renuka
Qingbei Zhang3,6., Sajid
(microRNAs
metastatic tumors, Table 1a) and
accurately
separate, Xinan
oligometastatic
and
polymetastatic
patients , Thomas
high-dose5 radiotherapy.
5
6
5
5
3
17
Pr-miRs (microRNAs
prioritized
(Fig. S1). Perakis
Indeed, unsupervised
not designed
to
, Matthewmethods
Filippoare, Kimberly
Corbin
, Younghee
Lee , Mitchell
C. from primary tumors,
Malik , Hanli Fan , Samantha
Table
1b). To validate
Pr-miR
and M-miR,
we applied
them
identify5a phenotype,
such as the
subtle
distinction
between
oligo- 1,2,5
7
2,5
Results:
Patients
who
failed
to
develop
polymetastases
are
characterized
by
unique
prioritized
features
of a microRNA
*
Posner , Steven J. Chmura , Samuel Hellman , Ralph R. Weichselbaum
to patients
in the alternative dataset (ie Pr-miR
wasmodel
tested in
in which
the
and poly-metastases,
while
the primary
tumor cells family.
are more
classifier that
includes
the microRNA-200
We created
an oligometastatic-polymetastatic
xenograft
1 Comprehensive Cancer Center, University
of Chicago,
Chicago,
United
States ofWe
America,
Center for
Metastasis
Research,
University
Chicago, and M-miR in the patients
patients
with
metastatic
tissueofobtained
heterogeneous
than
thoseIllinois,
of microRNAs
metastases.
thus2 Ludwig
obtained
the patient-derived
discriminated
between
the
two metastatic
outcomes.
MicroRNA-200c enhancement in an
Chicago, Illinois, United States of America, 3 Department of Medicine Center for Biomedical Informatics, University of Chicago, Chicago, Illinois, United States of America,
with primary tissue profiled). This analysis was performed using
microRNA oligometastatic
profiles of 5 patients
whom in
both
primary andprogression.
cell lineforresulted
polymetastatic
4 Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, United States of America, 5 Department of Radiation and Cellular Oncology,
the unsupervised first component of a principal component
metastatic samples were collected. In MicroRNA
four of fiveCharacterizes
patients primary
Oligometastasis(es)
University of Chicago, Chicago, Illinois, United States
of America, 6 Department
of Pathology
Committee on
Biology,basis
University
ofoligometastases
Chicago, Chicago, Illinois,
United
Conclusions:
These
demonstrate
a Cancer
biological
for(PCA)
a potential
for different
using microRNA
analysis
(Methods, and
Methods
S1). At
cutoff
and metastatic
tumor samples,
theresults
microRNA
of the same
patient
States of America, 7 Department of Surgery, University
of
Chicago,
Chicago,
Illinois,
United
States
of
America,
8
Department
of
Radiation
Oncology
Duke
University
expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.
MicroRNA Expression Characterizes Oligometastasis(es)
Medical Center, Durham, North Carolina, United States of America
Abstract
andb.metastasis(es)
sample sitesby
of Expression
the same patient
andof
(ii)Oligooligo vs Polymetastases in Human Metastatic and Primary
Table 1. a(Pr)
and
Prioritized microRNAs
Analysis
Citation:
YA, Xing HR,(Pol-)
Salama
JK, Khodarevphenotype
NN, Huang across
Y, et al. patients.
(2011) MicroRNA Expression Characterizes Oligometastasis(es). PLoS ONE 6(12): e28650.
(Ol-) vsLussier
polymetastatic
progression
Tumors.doi:10.1371/journal.pone.0028650
doi:10.1371/journal.pone.0028650.g001
Editor: Mikhail V. Blagosklonny, Roswell Park Cancer Institute, United States of America
Background: Cancer staging
and
a division
intoof11,
localized
or metastatic
Received
Octoberpresumes
10, 2011; Accepted
November
2011; Published
Decemberdisease.
13, 2011 We proposed an
Table 1a. Oligo
vs polymetastases
progression
in metastatic
tumor samples (M-miRs)
Intreatment
vivo
assessment
of
the effect
microRNA-200c
intermediate state defined byCopyright:
#5 cumulative
metastasis(es),
oligometastases.
In contrast
tothewidespread
! 2011 Lussier
et al. This is antermed
open-access
article distributed under
the terms of
Creative Commons Attribution License, which permits
miRIDIAN
mimics
treatment
metastatic
progression
in However,
MicroRNA
FC
pon
(t-test)
MicroRNA
FC patients
p (t-test)
polymetastases, oligometastatic
patients
maydistribution,
benefit
from
metastasis-directed
local
treatments.
unrestricted
use,
and reproduction
in any medium,
provided
the original
author andmany
source
are credited.
two
mouse
models
who initially present with
oligometastases
progress
to
polymetastases.
Predictors
of
progression
could
improve
patient
Funding: This work28.3
was supported by the Ludwig
Research Grant, the Center for Radiation
Therapy, the Chicago
miR-654-3p
0.028 Center for MetastasismiR-95
2.4
0.029 Tumor Institute, Dr. Lloyd
40%
confluent
L1-R2-435-GFP
cells orLung
B16F1
were
selection for metastasis-directedOld,
therapy.
Mr.
and Mrs.
Vincent Foglia
and the Foglia foundation,
Cancer cells
Research
Foundation, the Cancer Research Foundation and the following NIH Grants: K22
miR-654-5p
24.6
0.041
miR-500
22.1
LM008308-04,
5UL1RR024999-04,
Chicago(Cat#110CN-001000Comprehensive Cancer Center (5P30CA014599-35), National Center 0.047
for the Multi Scale Analysis of
transfected
with 100 nMUniversity
Control ofmimics
Genomicof
and
Cellular
Networks
(MAGNeT;
5U54CA121852-5).
The funders
had no role in
study design,
collection and analysis,
Methods: Here, we identified
patterns
microRNA
expression
of
tumor
samples
from
oligometastatic
patients
treated
miR-200c
20.1
0.029
miR-328
22.2datawith
0.002 decision to publish, or
01),
or
species-specific
miR-200c
miRIDIAN
mimics
(L1-R2-435of the manuscript.
high-dose radiotherapy. miR-105 preparation
GFP: #C-300646-05-0010;
B16F1:
(Dhar15.9
0.023 # MIMAT0000039)
miR-125a-3p
22.2
0.048
Competing Interests: The authors have declared that no competing interests exist.
macon,
Lafeyette,
CO,
USA)
using
Oligofectamine
(Invitrogen,
miR-375
14.9
0.027
miR-140-5p
0.024
Results: Patients who failed
to* develop
polymetastases
are characterized
by unique prioritized
features of a 22.2
microRNA
E-mail:
[email protected]
[email protected]
Carlsbad,
CA, USA) as we(RRW);
previously
described(YAL)
[22]. Transfection
miR-135b
0.013
miR-29c xenograft model
22.4
0.008
classifier that includes the
microRNA-200 family.7.8We created an oligometastatic-polymetastatic
in which
. These
authorswas
contributed
equally
to this work. to be .90%. In vivo tailefficiency
optimized
the patient-derived microRNAs
theand
twoestimated
metastatic
outcomes. MicroRNA-200c
enhancement
miR-200b discriminated between
5.7
0.032
miR-140-3p
22.4 in an
0.018
injection of progression.
control or specific mimics-treated L1-R2-GFP
oligometastatic cell line miR-410
resulted invein
polymetastatic
6
5
5.4
0.01
miR-489
22.7
0.008
(2610 cells/mouse) or B16F1 cells (1610 cells/mouse) was
it has only recently
received attention
Introduction
miR-376a
4.7
0.049
miR-331-5p
23.6
0.046 as a defined subset o
performed
at
48
h
after
transfection.
Conclusions: These results demonstrate a biological basis for oligometastases and a potential for using microRNA
metastasis [1,7,8]. Employing radiotherapy improvements, terme
For
model,
tumor-cell
mice
expression to identify patients
most
likelythe
to
remain
oligometastatic
metastasis-directed
treatment.
miR-323-3p
4.1
0.023after
miR-193a-3p
26.7
0.036
Metastases
areL1-R2-435-GFP
the leading
cause
of cancer
death.inoculated
Standard
hypofractionated image-guided radiotherapy (HIGRT) or stereo
were
monitored
and
scored
for
tumor
metastasis
development
and
miR-539
4
0.045
miR-199b-5p
29.5
0.043
therapies for most metastatic cancers are systemic chemotherapy,
tactic body radiotherapy (SBRT), we
[9] and others [8] treate
progression
as3.6
above.
For
the therapies.
B16F1
mouse
melanoma
Citation: Lussier YA, Xing HR, Salama
JK,
Khodarev
NN,
Huang
Y,described
et al.or
(2011)
MicroRNA
Expression
Characterizes
Oligometastasis(es).
PLoS
ONE
6(12):
e28650.
miR-642
0.024
miR-502-5p
218.3
0.034
hormonal
manipulation
newer
targeted
However,
metastatic lesions using a few high-doses of radiotherapy i
weeks curative.
C57BL/6We
female
mice that
wereduring
obtained
doi:10.1371/journal.pone.0028650
these model,
agents 4–6
are rarely
proposed
the frominoperable patients
Initial reports demon
miR-370
3.2
0.031
miR-545
220.2with #5 metastasis(es).
0.022
labs
(Indianapolis,
IN,
USA).
The
care
and
treatment
of
Editor: Mikhail V. Blagosklonny, Roswellevolution
Park Harlan
CancerofInstitute,
United
States
of
America
some
tumors,
an
intermediate
metastatic
state
exists
strated
long-term
disease
free
survival
in
some treated patien
miR-127-3p experimental 3 animals was in 0.04
miR-363
221.6
0.012
accordance with institutional
Received October 10, 2011; Acceptedcalled
November
11, 2011; Published
13, 2011 that these patients,
oligometastasis(es).
WeDecember
hypothesized
[8,9,10,11]. However, many oligometastatic patients develope
miR-212
2.7 University of Chicago.
0.002
guidelines
the
Mice were
sacrificed 14
a less at
aggressive
biology
with
cumulative
widespread
cancer
and were subsequently classified a
Copyright: ! 2011 Lussier et al. This exhibiting
is an open-access
article
distributed
under
the limited
terms of[1,2,3]
the Creative
Commons Attribution
License,
whichprogression
permits
days
after
tail
vein
injections.
The
thoracic
cavity
of
each (Pr-miRs)
mouse
unrestricted use, distribution, andTable
reproduction
in
any
medium,
provided
the
original
author
and
source
are
credited.
1b.
Oligo
vs
polymetastases
progression
in
primary
tumor
samples
metastasis(es) in less than 4 months from time of first metastatic
polymetastatic (.5 new metastatic sites, see methods). W
was opened andpotentially
lungs werebenefit
removed
in their entirety and surface
progression,
from
Funding: This work was supported
by the
Ludwig Centercould
for Metastasis
Research Grant,
Centermetastasis-directed
for Radiation Therapy,
the Chicago
Tumor Institute,
Lloyd
hypothesized
that
molecular
markers
could be developed fo
MicroRNA
FC were
p the
(t-test)
MicroRNA
FC Dr.
p (t-test)
lung
metastasis(es)
scored
using
methods
previously
describedand the following NIH
Old, Mr. and Mrs. Vincent Foglia and the Foglia
foundation,
Lung
Cancer
Research
Foundation,
Research
Foundation
Grants:
therapy [1,3]. This hypothesis was based the
on Cancer
long-term
survival
identifying patients
whoK22
would fail to become polymetastatic. W
LM008308-04, 5UL1RR024999-04,miR-654-3p
University of[23].
Chicago Comprehensive
Cancer Center
(5P30CA014599-35), National
Center for the Multi Scale
of
0.018
miR-127-3p
1.7Analysis
0.036 from paraffin blocks o
following
surgical 17
resection
liver
or and analyzed
microRNA
expression
derived
Genomic and Cellular Networks (MAGNeT;
5U54CA121852-5).
The
funders of
hadlimited
no role inlung
study[2],
design,
data[4,5],
collection
analysis, decision
to publish,
or
After
being
excised
from
each
mouse,
the
lung
tissue
was
fixed
14.3 from a variety
0.014 of primary sites.miR-24
21.5 oligometastatic0.014
adrenal metastases[6]
An
patients who were
at time of treatment wit
preparation of the manuscript. miR-542-3p
in 10% formalin,
embedded
inclinical
paraffin, cut into 5 micrometerscurative intent radiotherapy. We report unique prioritized feature
oligometastatic
common
miR-548c-3p
10 is a interests
0.001 presentation although
miR-27b
21.6
0.025
Competing Interests: The authors
have
declared that nostate
competing
exist.
sections, stained with hematoxylin and eosin and examined for
miR-758
8.8
0.045
miR-197
21.9
0.032
* E-mail: [email protected]
(RRW); [email protected]
macro- or (YAL)
micrometastases.
5 mice
were examined from
each
miR-483-5p
3.6
0.038
miR-330-3p
22
0.01
. These authors contributed equally to this work.
group.
PLoS ONE | www.plosone.org
1
December 2011 | Volume 6 | Issue 12 | e2865
miR-369-3p
3.6
0.047
miR-671-3p
22.2
0.012
REVIEWS
Definicióndeoligometástasis
Table 1 | Studies defining oligometastatic prostate cancer
Author/Site
n
Number of Sites of
metastases metastases
Detection
Tabata et al.27
35
≤5
Bone only; each
site <50% size of
vertebral body
Bone scan
Ahmed et al.28
17
≤5
NS
11
Berkovic et al.29
24
≤3
Bone or LN
• Bone scan + 18F-FDG PET–CT(n = 20)
• Bone scan + 11C-choline PET–CT(n = 4)
Schick et al.30
50
≤4
NS
• Bone scan + 18F-choline PET–CT
• Bone scan + 11C-acetate PET–CT
Decaestecker et al.31
50
≤3
Bone or LN
• 18F-FDG PET–CT(n = 32)
• 18F-choline PET–CT (n = 18)
Ost et al.32
119 ≤3
Any
18
NR
Any except
brain —JJ.Nature rev Urology,2016
Tososian
Original studies
C-choline PET–CT (n = 7), MRI (n = 6),
biopsy (n = 1), CT (n = 1), 11C-choline
PET–CT and MRI (n = 2)
F-FDG PET–CT (n = 24) or 18F-choline
PET–CT (n = 92)
Prospective trials (NCTI)
University of Florida (NCT01859221)33
NS
Schick et al.30
50
≤4
NS
• Bone scan + 18F-choline PET–CT
• Bone scan + 11C-acetate PET–CT
Decaestecker et al.31
50
≤3
Bone or LN
• 18F-FDG PET–CT(n = 32)
• 18F-choline PET–CT (n = 18)
Ost et al.32
119 ≤3
Any
18
University of Florida (NCT01859221)33
NR
NS
Any except brain
or CNS
—
Sunnybrook Health Sciences Centre
(NCT02563691)34
NR
≤5
Outside the
prostate and
pelvic lymph
nodes
—
Sidney Kimmel Comprehensive Cancer NR
Center (NCT02489357)35
≤4
Extrapelvic
—
Mayo Clinic (NCT01777802)36
NR
≤3
NS
—
Grupo de Investigación Clínica
en Oncología Radioterapia
(NCT02192788)37
NR
≤4
Bone, LN
—
University Hospital, Ghent
(NCT01558427)38
NR
≤3
NS (N1, M1a/b)*
—
Technische Universität Dresden
(NCT02264379)39
NR
≤5
NS
—
City of Hope Medical Center
(NCT00544830)40
NR
≤5
NS (N1–3, M1)
—
Memorial Sloan Kettering Cancer
Center (NCT02020070)41
NR
≤10
Bone, LN
—
≤3
Bone, LN
—
Definicióndeoligometástasis
F-FDG PET–CT (n = 24) or 18F-choline
PET–CT (n = 92)
Prospective trials (NCTI)
Sidney Kimmel Comprehensive Cancer NR
Center (ORIOLE) (NCT02680587)42
CNS, central nervous system; FDG, fluorodeoxyglucose; LN, lymph node; NCTI, national clinical trial identifier; NR, not reported;
NS, not specified; ORIOLE, Phase II randomized Observation versus stereotactic ablative RadiatIon for OLigometastatic Prostate
Tososian
JJ.Nature
rev
CancEr. *N1 = Metastases in regional lymph nodes; M1 = Distant metastasis; M1a
= Non-regional
lymph nodes;
M1bUrology,2016
= Bone;
¿quéopinanlosexpertos?
PSADTyriesgodemetástasis
RelaIonship)between)PSADT)and)the)risk)of)metastasis)or)death)
From!a!PSAUDT!<6!months!the!risk!of!metastasis!increases!exponenCally
was that conventional imaging tools—contrast enhanced
abdominopelvic computed tomography (CT) and Tc99mmethylene diphosphonate bone scintigraphy—perform
poorly in accurate staging of metastatic prostate cancer.
Clearly, if one fails to identify all sites of disease, then an
aggressive MDT approach to only those sites identified may
result in futile use of MDT ablative therapy [4]. MDT
strategies have seen an enormous boost with the advent of
superior imaging such as whole-body magnetic resonance
imaging (MRI) or positron-emission tomography (PET)/CT
with 18F and 11C-choline or 68Ga–prostate-specific membrane antigen (PSMA), as this would appear to perform
much better in identification of metastatic prostate cancer,
particularly at low levels of prostate-specific antigen (PSA)
in step with growth in publications regarding Ga-PSMA
PET/CT in recent years (Fig. 1). One might speculate that
enthusiasm for MDT is being fed by enthusiasm for
Ga68!PSMA PET imaging; a type of ‘‘oligometmania’’ akin
to the ‘‘Pokemania’’ described above. Physicians should be
reminded, however, that better does not mean perfect.
Diagnostic accuracy is indeed a key factor for success: is
what you see cancer and, more importantly, is there no
more cancer? In a recent paper by Montorsi et al [6], only
two-thirds of patients with positive 11C-choline or PSMA
PET/CT with oligo recurrent lymph nodes had cancer at
final pathology.
However, improved ability to identify metastatic lesions
does not necessarily imply that aggressive approaches to
Diagnósticodelaenfermedadoligometastásica
•
•
•
•
•
•
PSA
TAC
R.óseo
MRI
MRcuerpocompleto
PET:
•
•
•
•
•
•
•
Glucose consumption:(18)F]FDG
Cell membrane proliferation (phospholipids):(11)C](18)Fcholine ]
Synthesis offatty acids:(11)Cacetato.
Transp.Aminoacids andprotein synt.:(11)CmeIonine
Expres.Androgenic Receptor:(18)F]FDHT.
Osteoblast AcCvity:(18)F]fluoride.Na
Prostare specific membrane antigen:PSMA
• CTC
• DNAcirculante
Fig. 2 – ‘‘Pokemet’’ strategy using stereotactic ablative body radiotherapy (SABR) with ongoing biochemical and clinical progression. Images for a 67-yrold male at 2 yr after robot-assisted radical prostatectomy for pT3a Gleason grade group 2 prostate cancer with negative pathological margins. (A)
Prostate-specific antigen (PSA) 0.4 ng/ml; prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) demonstrates avidity in a
solitary 5-mm left obturator lymph node (in green); the patient underwent SABR. (B) PSA continued to rise to 0.6 ng/ml; repeat PSMA PET revealed no
avidity in the treated node, but a newly avid node in the left external iliac region, which was treated with a further course of SABR. (C,D) PSA further
increased to 1.1 ng/ml and PSMA PET revealed newly avid presacral nodes, with no avidity in previously treated nodes. Androgen deprivation therapy
was then offered. (E) Graph of biochemical progression for the 68Ga PSMA scans depicted in (A–D).
Please cite this article in press as: Murphy DG, et al. ‘‘Gotta Catch ’em All’’, or Do We? Pokemet Approach to Metastatic Prostate
Cancer. Eur Urol (2017), http://dx.doi.org/10.1016/j.eururo.2017.02.036
0
2
5
5
cue treatments while also scientifically establishing their
Whole-body
resonance imaging
0
2 diffusion-weighted
2
2 magnetic
true role in properly assessing the disease.
(WB-DW-MRI) vs choline-positron emission
It is essential to keep in mind that to select these
tomography-computed tomography (choline-PET/CT)
patients,
in addition
for
selecting
treatments
prostate
cancerto the latest imaging techniques,
ess
evidence
available
regarding in
the recurrent
use of
clinical predictors of limited disease must also be considRI. Even though is it1 is estimated to be equally
1
1
A.
G. Herrando-Parreño
R. Muelas-Soria
ered. These
include the time from primary tumour treat11 J. Conde-Moreno2
3
2
C-choline-PET/CT
at detecting M.bone
J. Ferrer-Rebolleda
R. Broseta-Torres
P. Cozar-Santiago
ment to the appearance metastases, the type of primary
F. Garcı́a-Piñón4 C. Ferrer-Albiach1
•
•
•
•
•
•
•
Received: 20 September 2016 / Accepted: 11 October 2016 / Published online: 31 October 2016
! Federación
de Sociedades Españolas de Oncologı́a (FESEO) 2016
ivity,
specificity,
Choline-PET/CT
in lymph node
metastases
Abstract
Valuewith
(%) multipleCI
95%
WB-DW-MRI
were excluded
Valuefrom
(%) the study.
CI 95%
WB-DW-MRI and choline-PET/CT was then performed on
Objective To determine the effectiveness of whole-body
each patient within 1 week. The results were interpreted by
diffusion-weighted magnetic resonance imaging (WB-DWSensitivity
100.00
98.98–100.00
18.37
6.51–30.23
specialists in nuclear medicine and MRI. If they were
MRI) in detecting metastases by comparing the results with
candidates for69.98–100.00
treatment with ablative100.00
SBRT (SABR), they
those from choline-positron
emission tomography-com-88.24
Specificity
97.09–100.00
were then evaluated every three months with both tests.
puted tomography (choline-PET/CT) in patients with bioPositive
predictive
value and no96.08Results Choline-PET/CT
89.77–100.00
100.00in 16 patients
94.44–100.00
detected lesions
chemical relapse after
primary
treatment,
observable using WB-DW-MRI.
metastases in bone scintigraphy,
CT and/orvalue
pelvic MRI, or
Negative predictive
100.00that were not 96.67–100.00
29.82 The results
17.07–42.58
were consistent in seven patients and in three cases, a
metastatic/oligometastatic prostate cancer (PCa). Patients
lesion was observed using WB-DW-MRI that was not
with this disease profile who could benefit from treatment
detected with choline-PET/CT. The Kappa value obtained
with stereotactic
body
radiation
therapy
(SBRT)
were
Clin Transl Oncol (2017) 19:553–561
559
was 0.133 (p = 0.089); the sensitivity, specificity, positive
selected and their responses to these techniques were rated.
predictive value (PPV) and negative predictive value
Materials and methods This was a prospective, controlled,
Table involving
6 Sensitivity,
PPV and
NPV in
bone metastases
(NPV) of WB-DW-MRI were estimated at 44.93, 64.29,
unicentric study,
46specificity,
consecutive
patients
from
86.11, and WB-DW-MRI
19.15%, respectively. For choline-PET/CT
our centre who presented biochemical relapse
after
adjuCholine-PET/CT
Bone scintigraphy
patients, the sensitivity, specificity, PPV, and NPV were
vant, salvage or radical treatment with external beam
Value (%)
CI 95%97.10, 58.33,
Value
(%) and 77.78%,
CI 95% respectively.
Value (%)
CI 95%
93.06,
radiotherapy, or brachytherapy. After initial
tests (bone
Conclusions Choline-PET/CT has a high global sensitivity
scintigraphy, CT, pelvic MRI), 35 patients with
Sensitivity
88.00 11 patients
73.26–100.00
72.00
52.40–91.60
80.95
while WB-DW-MRI
has a high
specificity, and
so they are 61.78–100.00
oligometastases
or without them were selected.
Specificity
88.46
74.26–100.00
70.37
51.29–89.45
61.29
42.53–80.05
Positive predictive value
88.00
73.26–100.00
69.23
49.57–88.89
58.62
38.97–78.27
88.46
74.26–100.00
73.08
[email protected]
54.10–92.05
82.61
64.94–100.00
& A. J. Conde-Moreno
Negative predictive
[email protected]
G. Herrando-Parreño
[email protected]
R. Muelas-Soria
[email protected]
J. Ferrer-Rebolleda
[email protected]
value
C. Ferrer-Albiach
1
Radiation Oncology Department, Consorcio Hospitalario
Provincial de Castellón, Castellón, Spain
2
Nuclear Medicine Department, Eresa Hospital General de
Valencia, Valencia, Spain
3
MRI Department, Eresa-Hospital General de Castellón,
2016)
16!arCcles!1,309!paCents!were!analysed.!
•!✚!68Ga!PSMAUPET:!!
!  40%!primary!staging!!!
!  76%))for)biochemical)recurrence)(BCR).!
•!✚!68Ga!PSMAUPET!!for!BCR!increased!with!higher!
preUPET!PSA:!
$  !0U0.2ng/ml:!42%!
$  0.2U1ng/ml:58%!
$  !1U2!ng/ml:76%!!
$  >!2!ng/ml:95%!
•  A!shorter)PSA)doubling)Ime,!resulted!in!a!92%!68Ga!
PSMAPET!posiCvity!compared!to!65%!from!corresponding!
choline!PET!metaUanalyCcal!data.!
!
European!!Urology!7!0!(!2!0!1!6!)!9!2!6!–!9!3!7!
¿quéopinanlosexpertos?
FalsospositivosconPETcolina yPSMA-PET
• Correlacion PET-linfadenectomía:
• Passoni etal:PETcolina
• 35%falsospositivos
• 35%N+enlamismaárea
• 30%N+enotraárea
• Pfister etal:PETcolinayPSMAPET
• 21,9%falsospositivosPETcolina
• 17,9%falsospositivosPSMA-PET
• PSMAmejorquePETcolinaentodoslosparámetros
• Monstorsi etal:PETcolina
• 31,2%falsospositivos
tion differences), and treated men comprised <5% of the
study population. Nonetheless, consistent findings were
obtained using two different sophisticated analyses. Of
note, patients who underwent external beam radiation
therapy (EBRT) were excluded from these studies owing
to the lack of organ-site-specific coding for EBRT in
SEER data.
radiation, and 440 men (28.6%) who underwent other
treatment. Whether the study distinguished between
definitive or palliative treatment in the radiation
therapy group was not reported; this omission might
explain why outcomes in the radiation group mirrored
the primary ADT and other treatment groups, and
why radiation therapy was not considered in the same
Tratamientolocalenenf.metastásica
Table 2 | Retrospective data for local consolidative therapy of the primary tumour
Source
Study design
Inclusion
Intervention
OS*
CSS*
MVA
Additional
information
Culp et al.44
Population-based,
n = 8,185, median
follow-up period:
16 months
M1a–M1c
• RP (n = 245)
• BT (n = 129)
• NLT (n = 7811)
• 67.4%
• 52.6%
• 22.5%
P <0.001
• 75.8%
• 61.3%
• 48.7%
P <0.001
SHR (CSM)
• 0.38 (0.27–0.53; RP)
• 0.68 (0.49–0.93; BT)
• 1.00 (ref; NLT)
MVA includes:
Gleason score ≥8, T4,
PSA ≥20 ng/ml, AJCC
N1 (versus N0), AJCC
M stage (versus M1a),
year of diagnosis
Antwi et al.45
Population-based,
n = 7,858, median
follow-up period:
NR
M1a–M1c
• RP (n = 222)
• BT (n = 120)
• NSR (n = 7516)
• 82.0%
• 66.7%
• 43.6%
P <0.0001
• 84.7%
• 71.7%
• 54.6%
P <0.0001
aHR (CSM)
• 0.22 (0.27–0.28; RP)
• 0.40 (0.32–0.51; BT)
• 1.00 (ref; NSR)
MVA includes: age,
race, marital status,
tumour grade, PSA
level, and cancer
registry
Gratzke
et al.46
Population-based,
n = 1,538, median
follow-up period:
NR
M+
• RP (n = 74)
• RT (n = 389)
• ADT (n = 635)
• Other (n = 440)
• 55% (RP)
• 21% (other
therapy)
P <0.01
• NR
NR
Overall survival
compared between RP
patients and non-RP
patients (including RT,
ADT, and other)
Satkunasivam
et al.47
Population-based,
n = 4,069, median
follow-up period:
NR
• M+
• Age
≥65 years
• RP (n = 47)
• IMRT (n = 88)
• CRT (n = 107)
• NLT (n = 3827)
• 73%
• 72%
• 37%
• 34%
• 79%
• 82%
• 49%
• 46%
aHR (CSM)
• 0.48 (0.27–0.85; RP)
• 0.38 (0.24–0.61; IMRT)
• 0.85 (0.64–1.14; CRT)
• 1.00 (ref; NLT)
• MVA includes:
sociodemographics,
primary tumour
characteristics,
CCI, ADT, and
bone radiation
within 6 months of
diagnosis.
• On CRR: SHR
(95% CI) for PCSM
versus NLT:
• RP 0.58 (0.35–0.95),
IMRT 0.43 (0.27–0.68)
Heidenreich
et al.48
Case-control,
n = 61, median
follow-up period:
• 40.6 months (RP)
• 44.0 months
(no RP)
Limited
M1
• RP (n = 23)
• No RP (n = 38)
• 91.3%
• 78.9%
P = 0.048
• 95.6%
• 84.2%
P = 0.043
• NR
Inclusion criteria:
≤3 lesions on bone
scan; absence of
visceral or extended
LN metastases;
PSA nadir <1 ng/
ml after 6 months of
neoadjuvant ADT
Cho et al.49
Case-control,
n = 140 (38 cases),
median follow-up
period: 34 months
M1
• RT (n = 38)
• No RT (n = 102)
• 69%
• 43%
• NR
HR (OM)
• 0.43 (P = 0.015)
MVA includes:
ECOG status, site of
metastasis
ADT, androgen deprivation therapy; aHR, adjusted hazard ratio; AJCC, American Joint Committee on Cancer; BT, brachytherapy; CCI, Charlson comorbidity
index;
VOLUME14|JANUARY2017
Methods!
The!NCDB!was!queried!for!men!with!newly!diagnosed!mPCa,!all!treated!with!ADT,!with!
complete!datasets!for!RT,!surgery,!prostateUspecific!anCgen!(PSA)!level,!Gleason!score,!and!
CharlsonUDeyo!comorbidity!score.!OS!was!analyzed!using!the!KaplanUMeier!method,!logUrank!
test,!Cox!proporConalhazards!models,!and!propensity!scoreUmatched!analyses.!
Results!
From2004!to!2012,!6,382menwithmPCawere!idenCfied,!including!538!(8.4%)!receiving!prostate!
RT.!At!a!median!followUup!of!5.1!years,!the!addiCon!of!prostate!RT!to!ADT!was!associated!with!
improved!OS!on!univariate!(P!,!.001)!and!mulCvariate!analysis!(hazard!raCo,!0.624;!95%!CI,!
0.551!to!0.706;!P!,!.001)!adjusted!for!age,!year,!race,!comorbidity!score,!PSA!level,!Gleason!
score,!T!stage,!N!stage,!chemotherapy!administraCon,!treaCng!facility,!and!insurance!status.!
Propensity!score!analysis!with!matched!baseline!characterisCcs!demonstrated!superiormedian!
(55!v!37months)!and!5Uyear!OS!(49%!v!33%)!with!prostate!RT!plus!ADT!compared!with!ADT!
alone!(P,!.001).!Landmark!analyses!limited!to!longUterm!survivors!of!$1,!$3,!and!$5!years!
demonstrated!improved!OS!with!prostate!RT!in!all!subsets!(all!P!,!.05).!Secondary!analyses!
comparing!the!survival!outcomes!for!paCents!treated!with!therapeuCc!dose!RT!plus!ADT!versus!
prostatectomy!plus!ADT!during!the!same!Cme!interval!demonstrated!no!significant!differences!
in!OS,!whereas!both!therapies!were!superior!to!ADT!alone.!
Conclusion!
In!this!large!contemporary!analysis,!men!with!mPCa!receiving!prostate!RT!and!ADT!lived!
substanCally!longer!than!men!treated!with!ADT!alone.!ProspecCve!trials!evaluaCng!local!
therapies!for!mPCa!are!warranted.!
•
Time to next skeletal-related event defined by even a fracture or bone pain requiring radiation
therapy or spinal cord compression or preventive surgery to the bones. Events will be
evaluated by investigators. No systematic X-Ray will be perform.
Time to chemotherapy
Time to severe local symptoms (grade 3 and 4 events according to NCI-CTCAE v4.0)
Impact of the radiotherapy protocol on outcome (PFS and local symptoms)
Toxicity (with a specific focus on the use of long-term low-dose steroids) according to NCICTCAE v4.0
Prostate cancer specific survival
ValortratamientolocalenpacientesM1:
PEACE-1TRIAL
•
•
•
•
•
STUDY SCHEME:
Metastatic hormone-naïve prostate cancer
patients
Verification of the eligibility criteria
RANDOMIZATION
Arm A: ADT
Arm B: ADT +
abiraterone 1000mg/day+
prednisone 5mg bid
Arm C: Arm A
+ radiotherapy
Arm D: Arm B +
radiotherapy
Linfadenectomía derescate:experiencias
Reviews; OligoM+ ganglionar; LDN de rescate
Abdollah etal;Eur Urol 2015;67:839-849
Supervivenciasegúnlocalizacion delas
metástasis
Site of Visceral Metastases Predicts Overall Survival
A
1.0
Median OS (months, 95% CI)
LN
31.6 (27.9 to 35.5)
Bone 21.3 (20.8 to 21.9)
Lung 19.4 (17.8 to 20.7)
Liver 13.5 (12.7 to 14.4)
OS (probability)
0.8
0.6
0.4
0.2
0
6
12
24
30
36
42
48
Time Since Random Assignment (months)
No. at risk
LN
18
565
510
424
345
250
162
91
50
37
Bone
6,356
5,602
4,406
3,079
1,932
1,083
556
278
165
Lung
791
669
508
347
225
126
65
36
16
Liver
752
551
367
219
128
66
27
13
5
B
Study
SWOG 9916
No. of patients (No. of deaths)
TAX 327
Median OS (months, 95% CI)
Bone (+/– LN)
Lung
17.3 (15.9 to 20)
245 (160)
21.1 (18.9 to 26.1)
16.2 (11.2 to NR)
25 (16)
20.9 (13.0 to NR)
Hazard Ratio* (95% CI)
1.12 (0.67 to 1.88)
J Clin Oncol 34:1652-1659.
1.19 (0.73 to 1.94)
Resultadosdelinfadenectomía derescatecon
PETcolinapositivos
Metastasis surgery
Table 1. Main results of studies reporting on salvage lymph node dissection in patients with PET/CT scan detected nodal
recurrence of prostate cancer
Study
Pts. (n)
Jilg
et al. [26]
47
Tilki
et al. [27]
58
Rigatti
et al. [25]
72
PET/CT
tracer
11
C-/18F
choline
Rate of
Mean PSA ADT prior sLND limited Mean no.
5-year
5-year
Median
at sLND
to sLND
to pelvic
of LNs
cBR
BCR-free CR-free
follow-up
(ng/ml)
(%)
area (%)
removed rate (%) rate (%) rate (%) CSS (%) (months)
11.1
78.7
54.0
12
46.0
8.7
25.6
77.7
35.5
F-choline
9.8
47.0
39.7
18.6
22.4
0
35.9
71.1
39
C-choline
3.73
55.5
22.2
30.6
56.9
19.0
48.6
75.0
39.8
59.3
29.4
52.0
89.1
76.6
–
45.5a
46.9a
92.5a
20
18
11
11
C-choline
3.95
62.7
23.7
11.7
Suardi
59
Role
of[15]
salvage lymph node dissection in prostate cancer Heidenreich et al.
et al.
Karnes
et al. [29]
52
11
C-choline
4.0
34.7
76.9
23.8
local treatment
Table 2. Pre- and postoperative parameters associated
29.6ADT,
months,
androgen deprivation
BCR,oncological
biochemical recurrence;
completesalvage
biochemical
response; CR, clinical recurrence; CSS, cancer-specific survival;
withtherapy;
beneficial
outcomecBR,
following
LND
LNs,the
lymph
nodes; no, number; PSA, prostate-specific antigen; Pts, patients; sLND, salvage lymph node dissection.
ction of
first
based on multivariate analysis of various patient cohorts
a
Three-year
rate.
ithin or
outside
Preoperative parameters
Postoperative parameters
4.3% of patients
T were free of
11
PSA <4
Complete
biochemical
based
on evidence
ofng/ml
C-choline/18F-choline
PET/
specific mortality rate was 3.7%. Three-year BCRery only
group
response
to our cohort and all other
free, systemic therapy-free and clinical recurrencedationCTof [10].
adju-In contrast
Positive PET/CT signals in the
<3 positive lymph nodes at
studies
to date, 27 patients received adjufree survival rates for patients with cBR were 69.3,
it needs
to published
be
small pelvis only
salvage LND
vant radiotherapy
of regions with histopathological
77.0, and 75%, respectively.
ly resected
the
Gleason score <8
Absence of retroperitoneal
confirmation
of lymph node metastases lymph
and node
six metastases
The largest U.S. study of sLND was published by
spicious
on the
etal.CO-urology.2016
patients
had additional evidence of local PCA recurKarnes et al.Heidenreich
[35] and included
52 patients. During a
ghlighted
by the
Long-Term Outcome After Radical
Prostatectomy for Patients With Lymph Node
Positive Prostate Cancer in the Prostate Specific Antigen Era
Stephen A. Boorjian, R. Houston Thompson, Sameer Siddiqui, Stephanie Bagniewski,
Erik J. Bergstralh, R. Jeffrey Karnes, Igor Frank and Michael L. Blute*
From the Department of Urology and Division of Biostatistics (SB, EJB), Mayo Medical School and Mayo Clinic, Rochester, Minnesota
Purpose: While the incidence of lymph node positive prostate cancer has decreased during the prostate specific antigen era,
the optimal
treatment of these
in question.PROSTATE
We
the impact
of lymph
node metastases
on LYMPH
the
UTCOME AFTER
PROSTATECTOMY
FORpatients
LYMPHremains
NODE POSITIVE
CANCER
868 examined
OUTCOME
AFTER
PROSTATECTOMY
FOR
NODE POSITIVE PROSTATE CA
outcome of patients following radical prostatectomy and investigated prognostic factors that affect survival.
Materials and Methods: We identified 507 men treated with radical prostatectomy between 1988 and 2001 who had lymph
node positive disease. Of the 507 patients 455 (89.7%) were treated with adjuvant hormonal therapy. Median followup was
10.3 years (IQR 6.1–13.5). Postoperative survival rates were estimated using the Kaplan-Meier method and the impact of
various clinicopathological factors on outcome was analyzed using Cox proportional hazard regression models.
Results: Ten-year cancer specific survival for patients with positive lymph nodes was 85.8% with 56% of the men free from
biochemical recurrence at last followup. On multivariate analysis pathological Gleason score 8 –10 (p ! 0.004), positive
surgical margins (p ! 0.016), nondiploid tumor ploidy (p ! 0.023) and 2 or greater positive nodes (p ! 0.001) were adverse
predictors of cancer specific survival. Tumor stage, year of surgery and total number of nodes removed did not significantly
affect outcome. Adjuvant hormonal therapy decreased the risk of biochemical recurrence (p "0.001) and local recurrence
(p ! 0.004) but it was not associated with systemic progression (p ! 0.4) or cancer specific survival (p ! 0.4).
Conclusions: Radical prostatectomy may offer long-term survival to patients with lymph node positive prostate cancer.
Gleason score, margin status, tumor ploidy and the number of involved nodes predict survival, while the role of adjuvant
hormonal therapy continues to be defined.
Key Words: prostate, prostatic neoplasms, lymph node dissection, prostate-specific antigen, prostatectomy
A
s part of the stage migration in prostate cancer durNevertheless, a potential importance for addressing the priing the PSA era,1 the incidence of positive lymph
mary tumor in patients with advanced prostate cancer has
nodes in patients undergoing RRP has decreased to
been suggested.
approximately 4% in recent series.2,3 While lymph node
Moreover, because most patients with positive lymph
metastases
adversely
impact
the
prognosis
of
patients
folnodes
are currently
1. Outcome following RRP for patients with positive lymph nodes. LR, local recurrence. SP, systemic
progressionfound to have microscopic disease on
. 5. Postoperative CSS according to degree of lymph node involvement
lowing surgery, extended postoperative survival in a subset
pathological examination ofFIG
the
nodes after RRP, the appro2–7
of these men was reported.
However, studies to date of
priate postoperative treatment of such patients similarly
nodes
waslargely
56%, 89%,
and
BCR, local
recurRRP, of which
all were
given at
systemic
patients
with lymph
node
disease have
been
com-80% remains
We86%
next
examined
risk
factors for the
disease
progression
infor
question.
In particular
optimal
time toininiti-stage, year of surgery and the total
rence, systemic progression patients
and cancer
death,
respectively.
including chemotherapy in 1, strontium in 1
11,12
with therapy
positive lymph
nodes.
In debated.
a multivariate
Coxiden-examined did not affect survival.
posed of pre-PSA and early PSA era cohorts, when the clinate
hormone
continues
to
be
The
Postoperative survival was
thenonly
stratified
for allpreoperative
patients
in 2.
AHT was associated with a decrea
model
increased
PSA
(p
!
0.036)
and
icopathological
features
of
prostate
cancer
tend
to
be
more
tificationof of
risk factors
for disease progression in patients
who underwent RRP by the nondiploid
number
positive
lymph
an followup after RRP1of 10.3 years (IQR 6.1–
(p "0.001) and local recurrence (p ! 0.0
tumor ploidy
(p nodes
! 0.006) were significant predicadvanced.
with nodal disease
may help individualize treatment for
(figs. 2 to 5). Although a single
node significantly
ents had BCR, 51 experienced local recurrence,
significantly impact systemic progression
torsmetastatic
of BCR, while
pathological Gleason score 8 –10 was
While
mendied,
withincluding
lymph node
continue
to be
these
patients.
increased
the risk
of BCR
(HR
1.4,
95%
CI
1.1–1.7,BCR (p ! 0.078, table 3). A
mic relapse and
200 had
72 ofmetastases
(p ! 0.43). Ten-year event-free survival fo
associated with a trend toward
J.Urol,2007
Experienciasrestrospectivas
conSBRT
REVIEWS
Table 3 | Retrospective data for metastasis-directed radiotherapy
Source
Study design
Treated
cohort (% of
lesions)
Muacevic
et al.55
Case series,
n = 40, 64 lesions,
median follow-up
per od
ont s
Bone (100%)
Median dose
(range) and
fractions
1 fraction (80% of
patients)
Toxicity per
CTCAE (% of
lesions)
Median Clinical outcomes*
ADT-FS
(months)
NR
NR
2-year local control: 95.5%
Ahmed et al.28 Case series, n = 17, 21
• Bone (90%)
lesions, median follow- • LN (5%)
p per od
ont s
• Liver (5%)
• Dose: bone 20 Gy
(8–24); LN 50 Gy;
liver 60 Gy
• Median fractions:
bone 1 (1–3), LN 5,
liver, 3
• Grade 1 (9.5%)
• Grade 2 (9.5%)
•
rade
NR
• Local control: 100%
• 1-year FFDP: 40%
• 1-year CSS: 100%
Berkovic
et al.29
Case series, n = 24, 29
• Bone (55%)
lesions, median follow- • LN (45%)
p per od
ont s
• 50 Gy (40–50)
• Median fractions
10, range 8–10
• Grade 2 GI (8%)
• Grade 2 GU (6%)
•
rade
38
• 2-year local control: 100%
• 2-year CPFS: 42%
Schick et al.30
Case series n = 50, 79
• Bone (31.5%) • 64 Gy (44–78)
lesions, median follow- • LN (63.5%)
• Fractions NR
p per od
ont s
• Viscera (5%)
NR
• 3-year bRFS: 54.5%
• 3-year CPFS: 58.6%
• 3-year OS: 92%
25
• Local control: 100%
• Median PFS: 19 months
• 1-year and 2-year PFS: 64%, 35%
• 1-year and 2-year CSS: 96%, 90%
Decaestecker Case series, n = 50,
et al.31
70 lesions, median
follow-up period:
ears
• Bone (44%)
• LN (54%)
• Viscera (2%)
• Schedule 1: 50 Gy,
10 fractions
• Schedule 2: 30 Gy,
3 fractions
rade
• Grade 1 (14%)‡
• Grade 2 (6%) ‡
‡
•
rade
ADT, androgen deprivation therapy; ADT-FS, androgen deprivation therapy-free survival; bRFS, biochemical-relapse-free survival; CPFS, clinical progression-free
survival, CSS, cancer-specific survival; CTCAE, Common Terminology Criteria for Adverse Events; FFDP, failure from distant progression; LN, lymph node; NR, not
reported; NS, not specified; OS, overall survival; PCSM, prostate cancer-specific mortality; PFS, progression-free survival. *In cases of unspecified time frame,
values refer to proportion experiencing outcome during total follow-up period. ‡Percentage of patients.
or lymph node metastases using SBRT. Again, 2-year
rates of local control were 100%; clinical-progression
past few years have witnessed a flurry of research into
VOLUME14|JANUARY2017
REVIEWS
| UROLOGY
novel PETNATURE
radiotracers
targeting
lesions of
the bone and
Experienciasrestrospectivas
conSBRT
REVIEWS
Table 3 | Retrospective data for metastasis-directed radiotherapy
Source
Study design
Treated
cohort (% of
lesions)
Muacevic
et al.55
Case series,
n = 40, 64 lesions,
median follow-up
per od
ont s
Bone (100%)
Median dose
(range) and
fractions
1 fraction (80% of
patients)
Toxicity per
CTCAE (% of
lesions)
Median Clinical outcomes*
ADT-FS
(months)
NR
NR
2-year local control: 95.5%
Ahmed et al.28 Case series, n = 17, 21
• Bone (90%)
lesions, median follow- • LN (5%)
p per od
ont s
• Liver (5%)
• Dose: bone 20 Gy
(8–24); LN 50 Gy;
liver 60 Gy
• Median fractions:
bone 1 (1–3), LN 5,
liver, 3
• Grade 1 (9.5%)
• Grade 2 (9.5%)
•
rade
NR
• Local control: 100%
• 1-year FFDP: 40%
• 1-year CSS: 100%
Berkovic
et al.29
Case series, n = 24, 29
• Bone (55%)
lesions, median follow- • LN (45%)
p per od
ont s
• 50 Gy (40–50)
• Median fractions
10, range 8–10
• Grade 2 GI (8%)
• Grade 2 GU (6%)
•
rade
38
• 2-year local control: 100%
• 2-year CPFS: 42%
Schick et al.30
Case series n = 50, 79
• Bone (31.5%) • 64 Gy (44–78)
lesions, median follow- • LN (63.5%)
• Fractions NR
p per od
ont s
• Viscera (5%)
NR
• 3-year bRFS: 54.5%
• 3-year CPFS: 58.6%
• 3-year OS: 92%
25
• Local control: 100%
• Median PFS: 19 months
• 1-year and 2-year PFS: 64%, 35%
• 1-year and 2-year CSS: 96%, 90%
Decaestecker Case series, n = 50,
et al.31
70 lesions, median
follow-up period:
ears
• Bone (44%)
• LN (54%)
• Viscera (2%)
• Schedule 1: 50 Gy,
10 fractions
• Schedule 2: 30 Gy,
3 fractions
rade
• Grade 1 (14%)‡
• Grade 2 (6%) ‡
‡
•
rade
ADT, androgen deprivation therapy; ADT-FS, androgen deprivation therapy-free survival; bRFS, biochemical-relapse-free survival; CPFS, clinical progression-free
survival, CSS, cancer-specific survival; CTCAE, Common Terminology Criteria for Adverse Events; FFDP, failure from distant progression; LN, lymph node; NR, not
reported; NS, not specified; OS, overall survival; PCSM, prostate cancer-specific mortality; PFS, progression-free survival. *In cases of unspecified time frame,
values refer to proportion experiencing outcome during total follow-up period. ‡Percentage of patients.
or lymph node metastases using SBRT. Again, 2-year
rates of local control were 100%; clinical-progression
past few years have witnessed a flurry of research into
VOLUME14|JANUARY2017
REVIEWS
| UROLOGY
novel PETNATURE
radiotracers
targeting
lesions of
the bone and
ROPEAN UROLOGY 69 (2016) 9–12
nodal
dissection (n = 2), or chemotherapy (n = 3). The
Progression-free Survival FollowingE UStereotactic
Body
median time from first SBRT to the start of palliative
Radiotherapy for Oligometastatic Prostate Cancer
ADT was 28 mo (95% CI, 16.2–69.7). Reasons for starting
available at www.sciencedirect.com
Treatment-naive
palliativeAnalysis
ADT were biochemical progression (n = 2), oligoj o u r n a lRecurrence:
h o m e p a g e : w w w . e uA
r o pMulti-institutional
eanurology.com
UROLOGY
urvival
beam
n very
pically
[4].
into a
usions
is a
diagstases
entral
2014/
which
llows:
elapse
t, and
s were
/ml at
rogen
SBRT,
t with
rmone
maxiceived
n = 24)
with
onance
isease.
astatic
t least
) of at
of the
ion of
iation
dicate
radionation
owing
39 Gy
SBRT
e, and
rately
n-free
astatic
ogrese. The
DPFS,
(OS).
ential
nivarf SBRT
ely. All
metastatic progression (n = 18), or polymetastatic progresa,
b
c
d
sion
(n = 37).
Piet Ost *, Barbara Alicja Jereczek-Fossa , Nicholas Van As , Thomas Zilli
,
e
f
c
g
Seven
patients
, from PCa, and one patient died from
Alexander Muacevic , Kenneth Olivier , Daniel Henderson , Franco Casamassimadied
b
b
f
c
pancreatic
cancer.
The
, Alessia Surgo , Lindsay Brown , Alison Tree , Raymond Miralbell d3, and 5-yr OS was 95% and 88%,
6Roberto
9 ( 2 0 1 6 )Orecchia
9–12
respectively. Late grade 1 and 2 toxicity was observed in
Gert De Meerleer a
14% (n = 17) and 3% of patients (n = 3), respectively. The
a
Table
1 – Patient
characteristics
Department
of Radiotherapy,
Ghent University Hospital, Belgium; b University of Milan and European Institute of Oncology, Milan Italy; c Department of
d
reported
toxicity
was due to gastrointestinal
Radiotherapy Royal Marsden NHS Foundation Trust, London,
Department
of Radiation Oncology, Geneva
University grade
Hospital,2Geneva,
Switzerland;
Characteristics
AllUK;
patients
(n = 119)
e
g
Cyberknife Center Munich Grosshadern, Munich, Germany; f Department of Radiation Oncology, Mayocomplaints
Clinic, Rochester,
MN, USA;treated
Ecomedica
in patients
for nodal metastases. No
Platinum Priority – Brief Correspondence
Age at PCa diagnosis, yr
Radioterapia,
Empoli, Italy
Median (IQR)
61 (56–65)
toxicity of grade "3 was observed.
Follow-up from PCa diagnosis, yrEditorial by Vincent Khoo on pp. 13–14 of this issue
Median (IQR)
7.2 (5.0–9.3)
Primary
therapy, n (%)
Article info
Abstract
Radical prostatectomy alone
21 (17.6)
Radical prostatectomy with postoperative RT
37 (31.1)
Radical
prostatectomy with
31 (26.1)
Article
history:
The literature
on metastasis-directed therapy for oligometastatic prostate cancer (PCa)
postoperative RT and ADT
recurrence consists of small heterogeneous studies. This study aimed to reduce the
Accepted
July 2, 2015
Radiotherapy and ADT
22 (18.5)
heterogeneity
by pooling individual patient data from different institutions treating
Radiotherapy alone
8 (6.7)
oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed
Associate
Editor:
PSA
at initial
diagnosis, ng/ml
on patients
who
were treatment naive, with the aim of determining if SBRT could delay
Mean (range)
18.1
(1.3–180)
Giacomo
Novara
Median (IQR)
10.7 (6.8–19)
disease progression.
We included patients with three or fewer metastases. The KaplanUnknown
9
Meier method
was used to estimate distant progression-free survival (DPFS) and local
EAU prognostic grouping at initial diagnosis, n (%)
Keywords:
progression-free
survival
(LPFS). Toxicity was scored using the Common Terminology
Low
5 (4.2)
Criteria for
Events. In total, 163 metastases were treated in 119 patients. The
Prostatic
neoplasms
Intermediate
30Adverse
(25.2)
median DPFS
was 21 mo (95% confidence interval, 15–26 mo). A lower radiotherapy dose
High
51 (42.9)
Neoplasm
metastasis
Very high
(25.2)local recurrence rate with a 3-yr LPFS of 79% for patients treated with
predicted 30
a higher
Oligometastasis
Unknown
3
(2.5)
a biologically effective dose !100 Gy versus 99% for patients treated with >100 Gy
Interval
from
diagnosis to metastases, yr
Neoplasm
recurrence
(p = 0.01). Seventeen
patients (14%) developed toxicity classified as grade 1, and three
Mean (range)
5.0 (0.2–16.8)
patients (3%)
Radiosurgery
Median (IQR)
4.7developed
(2.7–6.6) grade 2 toxicity. No grade "3 toxicity occurred. These results
should
serve
as
a
benchmark
for future prospective trials.
PSA
level at first
documented
metastases, ng/ml
Stereotactic
body
radiotherapy
Patient summary:
This multi-institutional study pools all of the available data on the
Mean (range)
9.6 (0.1–116.7)
Median (IQR)
4.0 (1.6–8.8)
use of stereotactic
body radiotherapy for limited prostate cancer metastases. We
Unknown
1
a metastases, mo concluded that this approach is safeb and associated with a prolonged treatment
PSA DT at first documented
progression-free
survival.
Mean (range)
5.6 (1.0–30.0)
d
# 2015
Median (IQR)
3.9Published
(2.9–6.9) by Elsevier B.V. on behalf of European Association of Urology.
Unknown
36
e
f
No. of lesions at diagnosis of metastases, n (%)
* Corresponding
author. Department of Radiotherapy, Ghent University Hospital, De Pintelaan 185,
One metastasis
86 (72.3)
B-9000 Ghent,
Belgium. Tel. +32 3322411; Fax: +32 93323040.
Two metastases
22 (18.5)
E-mail address:
[email protected] (P. Ost).
Three metastases
11 (9.2)
Primary site of metastases, n (%)
Lymph nodes
72 (60)
Pelvic
53 (45)
state of cancer spread while avoiding or delaying the toxicity
Metastasis-directed
therapy is a lesion-targeted approach
Obturator
12 (10)
Internal for
iliac
9 (8)
associated with the use of systemic therapies [1]. A few
reserved
a subset of patients with a limited number
of
External iliac
17 (14)
small studies using stereotactic body radiotherapy (SBRT) for
metastases
(typically three or fewer or five or fewer),
Presacral
2 (2) soCommon
iliac
6 (5)
oligometastatic prostate cancer (PCa) recurrences have been
called
oligometastases,
and it aims to control an intermediate
Combination of nodal sites
7 (6)
Extrapelvic
12 (10)
http://dx.doi.org/10.1016/j.eururo.2015.07.004
Fig. 1 – Kaplan-Meier analysis depicting time
Both
7 (6)
0302-2838/# 2015 Published by Elsevier B.V. on behalf of European Association of Urology.
Bones, n (%)
43 (36)
Axial
22 (18)
Appendicular
17 (14)
Both
4 (3)
Viscera, n (%)
Liver
1 (1)
Lung
1 (1)
Node and/or bone and/or viscera, n (%)
2 (2)
Imaging modality at recurrence, n (%)
Choline PET-CT
92 (77)
FDG PET-CT
24 (20)
MRI
3 (3)
Adjuvant ADT, n (%)
No
59 (50)
Yes
60 (50)
Duration of ADT, mo, median (range)
2 mo (1–8 mo)
Progression-free Survival Following Stereotactic Body
Radiotherapy for Oligometastatic Prostate Cancer
Treatment-naive Recurrence: A Multi-institutional Analysis
b
c
Drafting of the
Critical revision
Jereczek-Fossa
sima, Orecchia
Statistical analy
Obtaining fundi
Administrative,
Supervision: Os
Other (specify)
ia, stock owne
filed, received,
the Prostate C
Urology Young
of the Researc
Daniel Hender
of the Royal M
Centre.
Funding/Suppo
Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland;
g
Appendix A
Ecomedica
Radioterapia, Empoli, Italy
Article info
Analysis and in
(eg, employme
d
Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA;
Meerleer.
relevant to the
Department of Radiotherapy, Ghent University Hospital, Belgium; University of Milan and European Institute of Oncology, Milan Italy; c Department of
Cyberknife Center Munich Grosshadern, Munich, Germany;
Henderson, Ca
including spec
Piet Ost *, Barbara Alicja Jereczek-Fossa , Nicholas Van As , Thomas Zilli ,
Alexander Muacevic e, Kenneth Olivier f, Daniel Henderson c, Franco Casamassima g,
Roberto Orecchia b, Alessia Surgo b, Lindsay Brown f, Alison Tree c, Raymond Miralbell d,
Gert De Meerleer a
Radiotherapy Royal Marsden NHS Foundation Trust, London, UK;
Acquisition of d
Financial discl
[(Fig._1)TD$IG]
a,
Study concept a
Abstract
Article history:
Accepted July 2, 2015
The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa)
recurrence consists of small heterogeneous studies. This study aimed to reduce the
heterogeneity by pooling individual patient data from different institutions treating
oligometastatic PCa recurrence with stereotactic body radiotherapyto(SBRT).
focussed
distant We
progression.
Associate Editor:
on patients who were treatment naive, with the aim of determining if SBRT could delay
Giacomo Novara
disease progression. We included patients with three or fewer metastases. The KaplanMeier method was used to estimate distant progression-free survival (DPFS) and local
Keywords:
progression-free survival (LPFS). Toxicity was scored using the Common Terminology
Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The
Prostatic neoplasms
median DPFS was 21 mo (95% confidence interval, 15–26 mo). A lower radiotherapy dose
Neoplasm metastasis
predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with
Oligometastasis
a biologically effective dose !100 Gy versus 99% for patients treated with >100 Gy
Neoplasm recurrence
(p = 0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three
patients (3%) developed grade 2 toxicity. No grade "3 toxicity occurred. These results
Radiosurgery
should serve as a benchmark for future prospective trials.
Stereotactic body radiotherapy
ADT = androgen-deprivation therapy; EAU = European Association of Urology;
Patient summary: This multi-institutional study pools all of the available data on the
DPFS21meses:18vs25siADT
MedianatiempoADT:28m
3yDPFS31%
Supplement
found, in the
eururo.2015
References
[1] Hellman S
13:8–10.
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Volume 13 / Issue 1 / January 2017 • Journal of Oncology Practice
ClinicalTrials.gov
Identifier and Trial Marne
Wo-
Estimated
Experimental Arm(s)
Primary End Point
Patients
Completion Date
Clement and Sweeney
14
Table 1, Summary of Select Clinical Trials Investigating Evaluation and Treatment of Oligometastatic Prostate Cancer
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Copyright © 2017 by American Society of Clinical O
ORIOLETRIAL:randomized phase II.
Eligibility
• ≤3 metastatic lesions (≤5 cm)
• Hormone-sensitive disease
• PSADT <15 months
• ECOG ≤2
Randomization
Observation
Day 1:
PSA, LDH, AP, T, ctDNA,
and rectal swab
Days 1–30:
Observation
Day 90:
PSA, LDH, AP, T, and ctDNA
Day 180:
Bone scan, CT, PSA, LDH,
AP, T, and ctDNA
1:2
SBRT
DCFPyL-PET–MRI or DCFPyL-PET–CT,
PSA,LDH, AP, T, CTC/ctDNA assays,
PBMC (ImmunoSEQ), and rectal swab
SABR
PSA, LDH, AP, T, ctDNA,
and PBMC (ImmunoSEQ)
Bone scan, CT, and DCFPyL-PET–MRI
or DCFPyL-PET–CT, PSA, LDH, AP, T,
CTC/ctDNA assays
Patients progressing on observation
can be crossed over o protocol
to receive SBRT
Figure 2 | Schema for the phase II Randomized Observation
versus
Stereotactic
Nature
Reviews
| Urology
Ablative RadiatIon for OLigometastatic Prostate CancEr (ORIOLE) trial. Men with
metachronous hormone-naive oligometastatic disease will be enrolled and dynamically
randomized to the schema as shown. AP, alkaline phosphatase; CTCs, circulating tumour
cells; ctDNA, cell-free circulating tumour DNA; LDH, lactate dehydrogenase; PBMC,
peripheral blood mononuclear cells; SABR, stereotactic ablative radiation; SBRT,
stereotactic radiation therapy; T, serum testosterone. ORIOLE is sponsored by the
National Cancer Institute (NCI) 1U01CA183031 and a Movember-PCF Challenge Award.
R
from surrogate measures such as th
these studies notably lack a compa
definitive data will become available
tion and reporting of prospective ra
(TABLE 1) such as the Belgian STOM
Baltimore ORIOLE trial42 (FIG. 2), whi
to assess clinical progression in me
receive SBRT versus observation. Sec
include local control, ADT-free surv
quality-of-life outcomes.
We would encourage future retro
spective studies to clearly distingui
men using ADT at baseline, and to pr
1-year ADT-free survival in those wh
pose that future studies define clinical
detection of a new metastatic lesion
of a clinically significant event (such
fracture) in a previously detected st
the limited time course over which su
would be reasonable to share median,
values for these outcomes.
Future directions and recommend
Existing data suggest that local and m
therapies are safe in men with metasta
Whether we should take an aggressive
static disease simply because it is avai
this approach actually helps patients s
ing. Only retrospective data exist in th
of these studies provide an appropri
for comparison. Thus, the reality is th
beginning to answer this question. In
ation, we make the following recomm
sidering an aggressive treatment appr
known metastatic disease.
As in other settings, only those
suffer mortality or substantial morb
disease should be considered for agg
Ensayobelga:FASEIISTOMP
Patients with an oligometastatic recurrence,
diagnosed on choline PET/CT
after localtreatment with curative intent
R
A
N
D
O
M
1:
1
A:activesurveillance
B:MTDfollowed by active
surveillance
Stratified: location ofmetastasis (node vs.bone metastases)andPSAdoubling time
(≤3vs.>3months).
Both surgery andSBRTareallowed asMDT.
Activesurveillance means 3-monthlyPSAtesting andre-imaging atPSAprogression.
Primary endpoint : ADT-freesurvival.ADTwill bestarted inboth arms attimeof
polymetastatic disease (>3metastatic lesions),localprogression or symptoms.
Secondary endpoints:progression-freesurvival,quality oflife,toxicity andprostatecancer specific survival.
Amododeconclusiones…
• Faltanresultadosclarossobreelposiblevalor
terapéuticodeltratamientolocalsobre
oligometástasis.
• Paraobtenerresultadosesnecesariohacerestudios
quetenganencuenta:
• Laspruebasdiagnósticas
• Losdiferentestratamientos
• Lasdiferentessituacionesclínicasylocalizacionesdelas
metástasis
• Mientrastantocuidadocon…
‘subirsealcarro’deformaacrítica
The bandwagon effect
Antonarakis
Localized
Disease
Therapy
Surgery/
Radiation
Systemic
Therapy
Oligometastatic
Disease
Widely Metastatic
Castrate-Resistant
Disease